Abigail Peairs - Academia.edu (original) (raw)
Papers by Abigail Peairs
Elsevier eBooks, 2013
Diets rich in antioxidants (AOX) are associated with reduced risk for chronic disease. Many chron... more Diets rich in antioxidants (AOX) are associated with reduced risk for chronic disease. Many chronic diseases have an underlying inflammatory component. As inflammation can be instigated and perpetuated by oxidative stress (OS), dietary AOX may reduce disease risk by attenuating inflammation. While large clinical trials have not provided overwhelming support for the efficacy of AOX supplementation in the general population, recent evidence suggests that AOX may have therapeutic value in populations experiencing elevated OS. Obesity is a chronic inflammatory condition characterized by overnutrition and excess fat accumulation, both of which contribute to OS and obesity-related chronic disease. The focus of this chapter is on the relationships between dietary AOX and inflammation in obesity and diet-induced inflammation.
PubMed, 2019
Objective: Adolescents with type 1 diabetes (T1DM) must consider multiple factors in diet plannin... more Objective: Adolescents with type 1 diabetes (T1DM) must consider multiple factors in diet planning, including glycemic control and cardiovascular disease prevention, while ensuring adequate nutrition for growth. We examined diet composition, quality, and compliance for two dietary patterns - the traditional Dietary Approaches to Stop Hypertension (DASH) and a modified version of DASH in this population. Methods and findings: Two feeding studies were conducted. First, adolescents with T1DM consumed their usual diet for 3 days followed by traditional DASH for 6 days. Next, DASH menus were adjusted to align with T1DM nutrition guidelines, and this modified DASH for Diabetes (DASH-D) was tested on a new group of adolescents with T1DM for 6 days, following 3 days of usual diet. Usual diet was measured via 24-hr dietary recalls. Dietary composition of DASH-D was compared to DASH and usual diet. Eighteen adolescents (9/group) participated. Compared to usual diet, intake of protein, fiber, fruit, vegetables, lean meats, and low-fat dairy were higher, while saturated fat and added sugar were lower, in DASH-D. Percent energy from fat was higher, and from carbohydrate lower, in DASH-D versus traditional DASH, with food group intake reflecting these patterns. Participants consumed 87% of foods provided for DASH, and 98% of foods provided for DASH-D. In both DASH iterations, participants met national guidelines for fat, saturated fat, fiber, and fruit/vegetable intake, while usual diet fell short of these recommendations. Conclusions: The novel DASH-D pattern meets guidelines and may be a viable option for achieving nutrition goals for adolescents with T1DM.
Journal of the Academy of Nutrition and Dietetics, Sep 1, 2012
PubMed, 2017
Objective: Glucose variability (GV) independently increases risk for vascular events in patients ... more Objective: Glucose variability (GV) independently increases risk for vascular events in patients with diabetes. The Dietary Approaches to Stop Hypertension (DASH) dietary pattern emphasizes fruits, vegetables, whole grains, lean meats, and low fat dairy and has the potential to reduce postprandial blood glucose (BG) excursions, however, its effect on GV is not known. The purpose of this work was to assess feasibility and collect preliminary data on the efficacy of the DASH diet on GV in adolescents with type 1 diabetes (T1D). Methods: Twenty one adolescents recruited from the Diabetes Center of Cincinnati Children's Hospital Medical Center with T1D (11-17y) participated in one of two phases of a controlled feeding study. The first phase tested the acceptability and blood glucose response to a traditional DASH diet (DASH) and the second phase tested a DASH diet specifically modified for diabetes (DASH-D) to improve glucose response to meals. For each phase, participants consumed first their usual diet, and then a controlled DASH diet while wearing continuous glucose monitoring (CGM) systems for 3 days of each diet. All foods were provided to the patients during the DASH dietary periods and 24 h dietary recalls were conducted during the usual diet periods to assess daily intake. Results: Sixteen participants (14.1 +/- 2.2y) were included in final analyses (DASH n=7, DASH-D n=9). Both DASH diets were significantly higher in fruits, vegetables, fiber, vitamin A, and % energy from protein than usual intakes. DASH was higher in carbohydrate (CHO) (60 vs. 50%) and lower in fat (21 vs. 36%) than usual intake, resulting in higher GV (Standard Deviation and Lability Index) and more low BG excursions (3 ± 2.8 vs. 7.1 ± 3.3, p=0.024). DASH-D was modified to better match CHO and fat content of patients' usual intakes in phase 1 (50/30/20 for CHO/fat/pro respectively, which resulted in no difference in GV between DASH-D and usual intake. There were also trends for lower average BG (144.1 vs. 168.9, p=0.072) and less percentage of time spent in the hyperglycemic range (39.3 ± 25.5 vs. 54.1 ± 19.4, p=0.07) on DASH-D compared to usual intake. Conclusion: The DASH dietary pattern tended to result in less hyperglycemia and an overall lower BG compared to usual care. Modifying a traditional DASH diet by increasing heart healthy fats improves glycemic response to DASH and may be beneficial for long term cardiovascular benefits in youth with T1D.
Nutrition Journal, Nov 7, 2011
Background: Studies show that obese individuals have prolonged elevations in postprandial lipemia... more Background: Studies show that obese individuals have prolonged elevations in postprandial lipemia and an exacerbated inflammatory response to high fat meals, which can increase risk for cardiovascular diseases. As epidemiological studies indicate an association between type of fat and circulating inflammatory markers, the purpose of this study was to investigate the acute effect of different fat sources on inflammation and oxidative stress in overweight and obese individuals. Methods: Eleven overweight and obese subjects consumed three high fat milkshakes rich in monounsaturated fat (MFA), saturated fat (SFA), or long-chain omega 3 polyunsaturated fat (O3FA) in random order. Blood samples collected at baseline, 1, 2, 4, and 6 hours postprandial were analyzed for markers of inflammation (soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP)), oxidative stress (8-epi-prostaglandin-F2α (8-epi) and nuclear factor-B (NF-B)), and metabolic factors (glucose, insulin, non-esterified free fatty acids, and triglycerides (TG)). Results: O3FA enhanced NF-kB activation compared to SFA, but did not increase any inflammatory factors measured. Conversely, SFA led to higher ICAM-1 levels than MFA (p = 0.051), while MFA increased TG more than SFA (p < 0.05). CRP increased while TNF-α and 8-epi decreased with no difference between treatments. Conclusions: While most of the inflammatory factors measured had modest or no change following the meal, ICAM-1 and NF-B responded differently by meal type. These results are provocative and suggest that type of fat in meals may differentially influence postprandial inflammation and endothelial activation.
Obesity, Jul 1, 2008
The objective of this study was to test the hypothesis that the inflammatory response to a high‐f... more The objective of this study was to test the hypothesis that the inflammatory response to a high‐fat, low‐carbohydrate weight loss diet (HF) we previously observed was due to oxidative stress. Nineteen overweight subjects (BMI > 27 kg/m2) were randomly assigned to either an antioxidant supplement (AS) (1 g vitamin C/800 IU vitamin E) or a placebo (P) group and provided with a HF for 7 days. Fasted pre‐ and post serum samples were measured for markers of inflammation (C‐reactive protein (CRP), interleukin‐6 (IL‐6), and monocyte chemoattractant protein‐1 (MCP‐1)), oxygen radical absorbance capacity (ORAC), and glucose, whereas urine was measured for oxidative stress (8‐epi‐prostaglandin‐F2α (8‐epi)). HF resulted in significant reductions in weight (−3.2%), glucose (−18.7%), and MCP‐1 (−15%) (all P < 0.01), with no difference between groups. There was a trend for a differential effect between groups for CRP as it decreased 32% in the AS group but increased 50% for P (P = 0.076). Inverse correlations were noted between initial values and changes in several inflammatory and oxidative stress markers, including CRP (r = −0.501), 8‐epi (r = −0.863), and ORAC (r = −0.546) (all P < 0.05). It was concluded that weight loss on a short‐term HF caused reduction of some but not all markers of inflammation. A role for oxidative stress in causing inflammation was not confirmed; however, longer term diet‐controlled studies are necessary to further explore the trend for a differential response in CRP with antioxidant supplementation.
Clinical and Experimental Immunology, Mar 24, 2009
Recent reports show that 5-amino-4-imidazole carboxamide riboside (AICAR), a pharmacological acti... more Recent reports show that 5-amino-4-imidazole carboxamide riboside (AICAR), a pharmacological activator of AMP-activated protein kinase (AMPK), inhibits the lipopolysaccharide (LPS)-induced production of proinflammatory cytokines. MRL/MPJ-Faslpr (MRL/lpr) mice show an intrinsic decreased threshold for the production of inflammatory mediators when stimulated. In our current studies, we sought to determine if AMPK activation would inhibit inflammatory mediator production in stimulated kidney mesangial cells. Cultured mesangial cells from MRL/lpr mice were treated with AICAR and stimulated with LPS/interferon (IFN)-γ. AICAR decreased dose-dependently inducible nitric oxide synthase (iNOS), cyclooxygenase-2 and interleukin-6 production in LPS/IFN-γ-stimulated mesangial cells. Mechanistically, AICAR inhibited the LPS/IFN-γ-stimulated PI3K/Akt signalling inflammatory cascade but did not affect LPS/IFN-γ-mediated inhibitory kappa B phosphorylation or nuclear factor (NF)-κB (p65) nuclear translocation. Treatment with the adenosine kinase inhibitor 5′-iodotubercidin blocked the ability of AICAR to activate AMPK and prevented AICAR from inhibiting the LPS/IFN-γ-stimulated PI3K/Akt pathway and attenuating iNOS expression. Taken together, these observations suggest that AICAR inhibits LPS/IFN-γ-induced Akt phosphorylation through AMPK activation and may serve as a potential therapeutic target in inflammatory diseases.
... 2007; 120 (3, Suppl 1): S3-S11. 2. Das. Is obesity an inflammatory condition? Nutrition. 2001... more ... 2007; 120 (3, Suppl 1): S3-S11. 2. Das. Is obesity an inflammatory condition? Nutrition. 2001; 17: 953-966. 3. Rifai N, Ridker P. Inflammatory markers and coronary heart disease. Curr Opin in Lipidol. 2002; 13 (4): 383-389. 4. Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. ...
Medicine and Science in Sports and Exercise, May 1, 2017
Body composition has been widely recognized as one of the many factors that could affect performa... more Body composition has been widely recognized as one of the many factors that could affect performance in the collegiate athlete, including body fat percentage and its changes across the competitive season. Zephyr Performance Systems have been used as a tool to measure physiological load in competitive athletes. Changes in body composition and fitness measures have been reported in female soccer athletes, but few have examined the relationship between them across the season, and their potential effect on post-season fitness measures. PURPOSE: The purpose of this study was to determine the relationship between physiological load and body composition across the season on the post-season performance of the Yo-Yo Intermittent Recovery Test 2 in Division I Female Soccer Athletes. METHODS: Thirty female soccer athletes, age (19.4 ± 1 year) with preseason body fat percentage (22.7 ± 5.3%), participated in the Yo-Yo Intermittent Recovery Test 2 (YYIR2) prior to their fall pre-season conditioning period. Body fat percentage was assessed pre and post-season using BodPod assessment. Zephyr Performance Systems were worn during home season games to quantify and record the athletes' physiological load, which was averaged over the season (AVEPL). Athletes completed a second YYIR2 at the conclusion of their post-season play and the change in the distance covered on this assessment from pre to post-season was recorded (ChangeDist). RESULTS: No differences were observed in YYIR2 or body fat percentage between pre and post-season. However, AVEPL was negatively correlated with pre to post-season change in distance covered (ChangeDist), r =-0.489, p =0.040. Linear regression analysis also revealed ChangeDist was inversely related to AVEPL (β =-0.448, p =0.048). When adjusted for age and pre to post-season change in body fat percentage (ChangeBF), AVEPL remained inversely related to ChangeDist (β =-0.446, p =0.037). CONCLUSIONS: Athletes with higher average physiological load across the season exhibited a decrease in performance on the post-season Yo-Yo Intermittent Recovery Test 2 when compared to pre-season, regardless of change in body fat percentage. Further research should be done to determine whether these results are due to a true decline in fitness levels or a decline in motivation to perform on the post-season assessment.
Arteriosclerosis, Thrombosis, and Vascular Biology, Jun 1, 2018
Objective-PAR2 (protease-activated receptor 2)-dependent signaling results in augmented inflammat... more Objective-PAR2 (protease-activated receptor 2)-dependent signaling results in augmented inflammation and has been implicated in the pathogenesis of several autoimmune conditions. The objective of this study was to determine the effect of PAR2 deficiency on the development of atherosclerosis. Approach and Results-PAR2 mRNA and protein expression is increased in human carotid artery and mouse aortic arch atheroma versus control carotid and aortic arch arteries, respectively. To determine the effect of PAR2 deficiency on atherosclerosis, male and female low-density lipoprotein receptor-deficient (Ldlr −/−) mice (8-12 weeks old) that were Par2 +/+ or Par2 −/− were fed a fat-and cholesterol-enriched diet for 12 or 24 weeks. PAR2 deficiency attenuated atherosclerosis in the aortic sinus and aortic root after 12 and 24 weeks. PAR2 deficiency did not alter total plasma cholesterol concentrations or lipoprotein distributions. Bone marrow transplantation showed that PAR2 on nonhematopoietic cells contributed to atherosclerosis. PAR2 deficiency significantly attenuated levels of the chemokines Ccl2 and Cxcl1 in the circulation and macrophage content in atherosclerotic lesions. Mechanistic studies using isolated primary vascular smooth muscle cells showed that PAR2 deficiency is associated with reduced Ccl2 and Cxcl1 mRNA expression and protein release into the supernatant resulting in less monocyte migration. Conclusions-Our results indicate that PAR2 deficiency is associated with attenuation of atherosclerosis and may reduce lesion progression by blunting Ccl2-and Cxcl1-induced monocyte infiltration. Visual Overview-An online visual overview is available for this article.
Carolina Digital Repository (University of North Carolina at Chapel Hill), 2017
In this longitudinal study we explored the relationships between plasma n-3 and n-6 polyunsaturat... more In this longitudinal study we explored the relationships between plasma n-3 and n-6 polyunsaturated fatty acids (PUFAs) and Δ5 and Δ6 desaturase activities (D5D and D6D, respectively) and fasting lipids in youth with type 1 diabetes (T1D). Methods-Incident cases of T1D in youth <20 years of age who were seen for a baseline study visit (N=914) and a 1-year follow-up visit (N=416) were included. Fasting blood samples were obtained at each visit and plasma phospholipid n-6 PUFAs were measured, which included linoleic acid (LA), dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA); n-3 PUFAs included αlinolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Estimated D5D and D6D were calculated as FA product-to-precursor ratios, where D5D= AA/DGLA and D6D = DGLA/LA. To examine the longitudinal relationships between long chain PUFAs, desaturase activities and fasting plasma lipids in youth with T1D mixed effects models were used for each individual PUFAs, D5D and D6D, adjusted for demographics, clinic site, diabetes duration, insulin regimen, insulin dose/kg, HbA1c, insulin sensitivity score, and body mass index with random effects to account for the repeated measurements. Findings-Favorable lipid associations were found between LA and low-density lipoprotein (LDL) cholesterol (β= −0.58, P<0.05); AA, plasma triglycerides (TG) (β= −0.04, P<0.05) and TG/ high-density lipoprotein (HDL)-C ratio (β= −0.04, P<0.05); and D5D, plasma TG (β= −0.2, P<0.05) and TG/HDL-cholesterol ratio (β= −0.23, P<0.05). Findings were mixed for the n-3 PUFAs and DGLA: ALA was positively associated with plasma TG (β= 0.33, P<0.05) and HDL cholesterol (β= 9.86, P<0.05); EPA was positively associated with total cholesterol (β= 8.17, P<0.05), LDL cholesterol (β=5.74, P<0.01) and HDL cholesterol (β= 2.27, P<0.01); and DGLA was positively associated with TG/HDL-cholesterol ratio (β= 0.05, P<0.05) Conclusion-Findings suggest that the most abundant PUFA, LA as well as its metabolic biproduct AA, may be important targets for CVD lipid risk factor reduction in youth with T1D.
Journal of Functional Morphology and Kinesiology, Sep 28, 2020
Body composition plays a key role in overall health and sports performance and its assessment is ... more Body composition plays a key role in overall health and sports performance and its assessment is an important part of many athletic programs. The purpose of this study was to describe longitudinal changes in body composition for collegiate female soccer players in order to provide data to inform future training and nutrition interventions for this population. A linear mixed-model (LMM) approach was used to analyze four years of pre-and post-season body composition data, including total mass, fat-free mass (FFM), fat mass, and body fat percentage (%BF) for 49 athletes. Athletes gained an average of 0.5 kg FFM during the season (p < 0.05) and increased total mass, FFM, fat mass, and %BF (2.5 kg, 1.1 kg, 1.7 kg, and 1.7%, respectively; p < 0.05) over four years. Freshmen experienced a 1.5 kg gain in total mass pre-to post-season (p < 0.05), while no changes in total mass or body composition were seen in other grade levels. Gains in %BF during the off season between Freshman and Sophomore years represented negative changes in body composition that should be addressed further. These results can help interdisciplinary athlete care teams optimize training programs in this population by understanding what changes are expected over multiple years. Normalizing these changes may also help the promotion of realistic body composition goals and the development of positive training and dietary habits.
Medicine and Science in Sports and Exercise, Jul 1, 2020
Journal of Immunology, Apr 1, 2010
Epigallocatechin-3-gallate (EGCG), a bioactive component of green tea, has been reported to exert... more Epigallocatechin-3-gallate (EGCG), a bioactive component of green tea, has been reported to exert anti-inflammatory effects in immune cells. EGCG has been shown to activate the metabolic regulator, AMP-activated protein kinase (AMPK). Mesangial cells from MRL/lpr lupus-like mice are hyper-responsive to immune stimulation and overproduce nitric oxide (NO) and other inflammatory mediators when stimulated. In our current studies, we sought to determine if EGCG would inhibit inflammation in AMPK deficient mesangial cells. Cultured mesangial cells from MRL/lpr mice were treated with siRNA for mouse Prkaa2-Design A, specific for AMP-activated protein kinase-alpha (AMPK-α) or siRNA negative control for mouse. After 48 hours, the cells were serum-starved for 2 hours, treated with 50 μM epigallocatechin-gallate (EGCG) for one hour, and stimulated with lipopolysaccharide (LPS)/interferon (IFN)-γ for 30 minutes. The addition of siRNA inhibited AMPK expression in mesangial cells. LPS/IFN-γ induced inflammatory mediator production (iNOS expression, supernatant NO, and interleukin-6) as expected. Interestingly, EGCG blocked inflammatory mediator production in the AMPK deficient cells suggesting EGCG inhibits inflammatory pathways independently of AMPK to decrease inflammatory mediatory production. Taken together, these studies show that EGCG attenuated inflammation in MRL/lpr mouse mesangial cells independent of AMPK.
Pediatric Hematology and Oncology, Nov 5, 2020
Historically, youth with sickle cell disease (SCD) were at risk for being underweight, but recent... more Historically, youth with sickle cell disease (SCD) were at risk for being underweight, but recent data suggests this population is replicating obesity trends of youth in the United States. The current observational study assessed the weight status and health behaviors of 44 adolescents and young adults with SCD via a self-report survey and chart review. Using height and weight data closest to survey completion date, 27% of participants were either overweight or obese. With respect to obesogenic risk behaviors, 77% ate fast food 1-3 times per week, 25% had no fruits/vegetables with any of their meals, 11% drank no water, and 57% watched 4 or more hours of television per day. Though more research is needed, this preliminary study adds to the SCD literature suggesting an emerging shift toward obesity in this population. As such, adolescents with SCD may benefit from interventions to decrease obesity risk factors as being overweight or obese has the potential to worsen SCD-related symptoms and complications.
The FASEB Journal, Apr 1, 2015
The Journal of Immunology
Epigallocatechin-3-gallate (EGCG), a bioactive component of green tea, has been reported to exert... more Epigallocatechin-3-gallate (EGCG), a bioactive component of green tea, has been reported to exert anti-inflammatory effects in immune cells. EGCG has been shown to activate the metabolic regulator, AMP-activated protein kinase (AMPK). Mesangial cells from MRL/lpr lupus-like mice are hyper-responsive to immune stimulation and overproduce nitric oxide (NO) and other inflammatory mediators when stimulated. In our current studies, we sought to determine if EGCG would inhibit inflammation in AMPK deficient mesangial cells. Cultured mesangial cells from MRL/lpr mice were treated with siRNA for mouse Prkaa2-Design A, specific for AMP-activated protein kinase-alpha (AMPK-α) or siRNA negative control for mouse. After 48 hours, the cells were serum-starved for 2 hours, treated with 50 μM epigallocatechin-gallate (EGCG) for one hour, and stimulated with lipopolysaccharide (LPS)/interferon (IFN)-γ for 30 minutes. The addition of siRNA inhibited AMPK expression in mesangial cells. LPS/IFN-γ indu...
Journal of Nutritional Science
Nutrients are an essential part of building and maintaining optimal health. Certain nutrient expo... more Nutrients are an essential part of building and maintaining optimal health. Certain nutrient exposure has been shown to be associated with many important health outcomes, although there is variability among studies. Despite the scientific efforts of many, it is unclear why some well-hypothesised nutrients lack sufficient evidence for clear association with health outcomes. One potential reason for conflicting results is that certain subgroups of patients benefit or are harmed more by adequate or inadequate exposure to certain nutrients. These subgroup-specific effects have historically not been studied, or if they are, it is often in a one-off type of approach where the investigator believes that a subgroup effect could exist based on limited previous data. In the era of big data, improvements can be made in efforts to generate new hypotheses for subgroups of patients and recommendations for precision nutrition can be made. In the present paper, we present a strategy for exploring s...
Diabetes management, 2019
Objective: Adolescents with type 1 diabetes (T1DM) must consider multiple factors in diet plannin... more Objective: Adolescents with type 1 diabetes (T1DM) must consider multiple factors in diet planning, including glycemic control and cardiovascular disease prevention, while ensuring adequate nutrition for growth. We examined diet composition, quality, and compliance for two dietary patterns-the traditional Dietary Approaches to Stop Hypertension (DASH) and a modified version of DASH in this population. Methods and Findings: Two feeding studies were conducted. First, adolescents with T1DM consumed their usual diet for 3 days followed by traditional DASH for 6 days. Next, DASH menus were adjusted to align with T1DM nutrition guidelines, and this modified DASH for Diabetes (DASH-D) was tested on a new group of adolescents with T1DM for 6 days, following 3 days of usual diet. Usual diet was measured via 24-hr dietary recalls. Dietary composition of DASH-D was compared to DASH and usual diet. Eighteen adolescents (9/group) participated. Compared to usual diet, intake of protein, fiber, fruit, vegetables, lean meats, and low-fat dairy were higher, while saturated fat and added sugar were lower, in DASH-D. Percent energy from fat was higher, and from carbohydrate lower, in DASH-D versus traditional DASH, with food group intake reflecting these patterns. Participants consumed 87% of foods provided for DASH, and 98% of foods provided for DASH-D. In both DASH iterations, participants met national guidelines for fat, saturated fat, fiber, and fruit/vegetable intake, while usual diet fell short *
Recent reports show that 5-amino-4-imidazole carboxamide riboside (AICAR), a pharmacological acti... more Recent reports show that 5-amino-4-imidazole carboxamide riboside (AICAR), a pharmacological activator of AMP-activated protein kinase (AMPK), inhibits the lipopolysaccharide (LPS)-induced production of proinflammatory cytokines. MRL/MPJ-Fas lpr (MRL/lpr) mice show an intrinsic decreased threshold for the production of inflammatory mediators when stimulated. In our current studies, we sought to determine if AMPK activation would inhibit inflammatory mediator production in stimulated kidney mesangial cells. Cultured mesangial cells from MRL/lpr mice were treated with AICAR and stimulated with LPS/interferon (IFN)-g. AICAR decreased dose-dependently inducible nitric oxide synthase (iNOS), cyclooxygenase-2 and interleukin-6 production in LPS/IFN-g-stimulated mesangial cells. Mechanistically, AICAR inhibited the LPS/IFN-g-stimulated PI3K/Akt signalling inflammatory cascade but did not affect LPS/IFN-g-mediated inhibitory kappa B phosphorylation or nuclear factor (NF)-kB (p65) nuclear translocation. Treatment with the adenosine kinase inhibitor 5Јiodotubercidin blocked the ability of AICAR to activate AMPK and prevented AICAR from inhibiting the LPS/IFN-g-stimulated PI3K/Akt pathway and attenuating iNOS expression. Taken together, these observations suggest that AICAR inhibits LPS/IFN-g-induced Akt phosphorylation through AMPK activation and may serve as a potential therapeutic target in inflammatory diseases.
Elsevier eBooks, 2013
Diets rich in antioxidants (AOX) are associated with reduced risk for chronic disease. Many chron... more Diets rich in antioxidants (AOX) are associated with reduced risk for chronic disease. Many chronic diseases have an underlying inflammatory component. As inflammation can be instigated and perpetuated by oxidative stress (OS), dietary AOX may reduce disease risk by attenuating inflammation. While large clinical trials have not provided overwhelming support for the efficacy of AOX supplementation in the general population, recent evidence suggests that AOX may have therapeutic value in populations experiencing elevated OS. Obesity is a chronic inflammatory condition characterized by overnutrition and excess fat accumulation, both of which contribute to OS and obesity-related chronic disease. The focus of this chapter is on the relationships between dietary AOX and inflammation in obesity and diet-induced inflammation.
PubMed, 2019
Objective: Adolescents with type 1 diabetes (T1DM) must consider multiple factors in diet plannin... more Objective: Adolescents with type 1 diabetes (T1DM) must consider multiple factors in diet planning, including glycemic control and cardiovascular disease prevention, while ensuring adequate nutrition for growth. We examined diet composition, quality, and compliance for two dietary patterns - the traditional Dietary Approaches to Stop Hypertension (DASH) and a modified version of DASH in this population. Methods and findings: Two feeding studies were conducted. First, adolescents with T1DM consumed their usual diet for 3 days followed by traditional DASH for 6 days. Next, DASH menus were adjusted to align with T1DM nutrition guidelines, and this modified DASH for Diabetes (DASH-D) was tested on a new group of adolescents with T1DM for 6 days, following 3 days of usual diet. Usual diet was measured via 24-hr dietary recalls. Dietary composition of DASH-D was compared to DASH and usual diet. Eighteen adolescents (9/group) participated. Compared to usual diet, intake of protein, fiber, fruit, vegetables, lean meats, and low-fat dairy were higher, while saturated fat and added sugar were lower, in DASH-D. Percent energy from fat was higher, and from carbohydrate lower, in DASH-D versus traditional DASH, with food group intake reflecting these patterns. Participants consumed 87% of foods provided for DASH, and 98% of foods provided for DASH-D. In both DASH iterations, participants met national guidelines for fat, saturated fat, fiber, and fruit/vegetable intake, while usual diet fell short of these recommendations. Conclusions: The novel DASH-D pattern meets guidelines and may be a viable option for achieving nutrition goals for adolescents with T1DM.
Journal of the Academy of Nutrition and Dietetics, Sep 1, 2012
PubMed, 2017
Objective: Glucose variability (GV) independently increases risk for vascular events in patients ... more Objective: Glucose variability (GV) independently increases risk for vascular events in patients with diabetes. The Dietary Approaches to Stop Hypertension (DASH) dietary pattern emphasizes fruits, vegetables, whole grains, lean meats, and low fat dairy and has the potential to reduce postprandial blood glucose (BG) excursions, however, its effect on GV is not known. The purpose of this work was to assess feasibility and collect preliminary data on the efficacy of the DASH diet on GV in adolescents with type 1 diabetes (T1D). Methods: Twenty one adolescents recruited from the Diabetes Center of Cincinnati Children's Hospital Medical Center with T1D (11-17y) participated in one of two phases of a controlled feeding study. The first phase tested the acceptability and blood glucose response to a traditional DASH diet (DASH) and the second phase tested a DASH diet specifically modified for diabetes (DASH-D) to improve glucose response to meals. For each phase, participants consumed first their usual diet, and then a controlled DASH diet while wearing continuous glucose monitoring (CGM) systems for 3 days of each diet. All foods were provided to the patients during the DASH dietary periods and 24 h dietary recalls were conducted during the usual diet periods to assess daily intake. Results: Sixteen participants (14.1 +/- 2.2y) were included in final analyses (DASH n=7, DASH-D n=9). Both DASH diets were significantly higher in fruits, vegetables, fiber, vitamin A, and % energy from protein than usual intakes. DASH was higher in carbohydrate (CHO) (60 vs. 50%) and lower in fat (21 vs. 36%) than usual intake, resulting in higher GV (Standard Deviation and Lability Index) and more low BG excursions (3 ± 2.8 vs. 7.1 ± 3.3, p=0.024). DASH-D was modified to better match CHO and fat content of patients' usual intakes in phase 1 (50/30/20 for CHO/fat/pro respectively, which resulted in no difference in GV between DASH-D and usual intake. There were also trends for lower average BG (144.1 vs. 168.9, p=0.072) and less percentage of time spent in the hyperglycemic range (39.3 ± 25.5 vs. 54.1 ± 19.4, p=0.07) on DASH-D compared to usual intake. Conclusion: The DASH dietary pattern tended to result in less hyperglycemia and an overall lower BG compared to usual care. Modifying a traditional DASH diet by increasing heart healthy fats improves glycemic response to DASH and may be beneficial for long term cardiovascular benefits in youth with T1D.
Nutrition Journal, Nov 7, 2011
Background: Studies show that obese individuals have prolonged elevations in postprandial lipemia... more Background: Studies show that obese individuals have prolonged elevations in postprandial lipemia and an exacerbated inflammatory response to high fat meals, which can increase risk for cardiovascular diseases. As epidemiological studies indicate an association between type of fat and circulating inflammatory markers, the purpose of this study was to investigate the acute effect of different fat sources on inflammation and oxidative stress in overweight and obese individuals. Methods: Eleven overweight and obese subjects consumed three high fat milkshakes rich in monounsaturated fat (MFA), saturated fat (SFA), or long-chain omega 3 polyunsaturated fat (O3FA) in random order. Blood samples collected at baseline, 1, 2, 4, and 6 hours postprandial were analyzed for markers of inflammation (soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP)), oxidative stress (8-epi-prostaglandin-F2α (8-epi) and nuclear factor-B (NF-B)), and metabolic factors (glucose, insulin, non-esterified free fatty acids, and triglycerides (TG)). Results: O3FA enhanced NF-kB activation compared to SFA, but did not increase any inflammatory factors measured. Conversely, SFA led to higher ICAM-1 levels than MFA (p = 0.051), while MFA increased TG more than SFA (p < 0.05). CRP increased while TNF-α and 8-epi decreased with no difference between treatments. Conclusions: While most of the inflammatory factors measured had modest or no change following the meal, ICAM-1 and NF-B responded differently by meal type. These results are provocative and suggest that type of fat in meals may differentially influence postprandial inflammation and endothelial activation.
Obesity, Jul 1, 2008
The objective of this study was to test the hypothesis that the inflammatory response to a high‐f... more The objective of this study was to test the hypothesis that the inflammatory response to a high‐fat, low‐carbohydrate weight loss diet (HF) we previously observed was due to oxidative stress. Nineteen overweight subjects (BMI > 27 kg/m2) were randomly assigned to either an antioxidant supplement (AS) (1 g vitamin C/800 IU vitamin E) or a placebo (P) group and provided with a HF for 7 days. Fasted pre‐ and post serum samples were measured for markers of inflammation (C‐reactive protein (CRP), interleukin‐6 (IL‐6), and monocyte chemoattractant protein‐1 (MCP‐1)), oxygen radical absorbance capacity (ORAC), and glucose, whereas urine was measured for oxidative stress (8‐epi‐prostaglandin‐F2α (8‐epi)). HF resulted in significant reductions in weight (−3.2%), glucose (−18.7%), and MCP‐1 (−15%) (all P < 0.01), with no difference between groups. There was a trend for a differential effect between groups for CRP as it decreased 32% in the AS group but increased 50% for P (P = 0.076). Inverse correlations were noted between initial values and changes in several inflammatory and oxidative stress markers, including CRP (r = −0.501), 8‐epi (r = −0.863), and ORAC (r = −0.546) (all P < 0.05). It was concluded that weight loss on a short‐term HF caused reduction of some but not all markers of inflammation. A role for oxidative stress in causing inflammation was not confirmed; however, longer term diet‐controlled studies are necessary to further explore the trend for a differential response in CRP with antioxidant supplementation.
Clinical and Experimental Immunology, Mar 24, 2009
Recent reports show that 5-amino-4-imidazole carboxamide riboside (AICAR), a pharmacological acti... more Recent reports show that 5-amino-4-imidazole carboxamide riboside (AICAR), a pharmacological activator of AMP-activated protein kinase (AMPK), inhibits the lipopolysaccharide (LPS)-induced production of proinflammatory cytokines. MRL/MPJ-Faslpr (MRL/lpr) mice show an intrinsic decreased threshold for the production of inflammatory mediators when stimulated. In our current studies, we sought to determine if AMPK activation would inhibit inflammatory mediator production in stimulated kidney mesangial cells. Cultured mesangial cells from MRL/lpr mice were treated with AICAR and stimulated with LPS/interferon (IFN)-γ. AICAR decreased dose-dependently inducible nitric oxide synthase (iNOS), cyclooxygenase-2 and interleukin-6 production in LPS/IFN-γ-stimulated mesangial cells. Mechanistically, AICAR inhibited the LPS/IFN-γ-stimulated PI3K/Akt signalling inflammatory cascade but did not affect LPS/IFN-γ-mediated inhibitory kappa B phosphorylation or nuclear factor (NF)-κB (p65) nuclear translocation. Treatment with the adenosine kinase inhibitor 5′-iodotubercidin blocked the ability of AICAR to activate AMPK and prevented AICAR from inhibiting the LPS/IFN-γ-stimulated PI3K/Akt pathway and attenuating iNOS expression. Taken together, these observations suggest that AICAR inhibits LPS/IFN-γ-induced Akt phosphorylation through AMPK activation and may serve as a potential therapeutic target in inflammatory diseases.
... 2007; 120 (3, Suppl 1): S3-S11. 2. Das. Is obesity an inflammatory condition? Nutrition. 2001... more ... 2007; 120 (3, Suppl 1): S3-S11. 2. Das. Is obesity an inflammatory condition? Nutrition. 2001; 17: 953-966. 3. Rifai N, Ridker P. Inflammatory markers and coronary heart disease. Curr Opin in Lipidol. 2002; 13 (4): 383-389. 4. Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. ...
Medicine and Science in Sports and Exercise, May 1, 2017
Body composition has been widely recognized as one of the many factors that could affect performa... more Body composition has been widely recognized as one of the many factors that could affect performance in the collegiate athlete, including body fat percentage and its changes across the competitive season. Zephyr Performance Systems have been used as a tool to measure physiological load in competitive athletes. Changes in body composition and fitness measures have been reported in female soccer athletes, but few have examined the relationship between them across the season, and their potential effect on post-season fitness measures. PURPOSE: The purpose of this study was to determine the relationship between physiological load and body composition across the season on the post-season performance of the Yo-Yo Intermittent Recovery Test 2 in Division I Female Soccer Athletes. METHODS: Thirty female soccer athletes, age (19.4 ± 1 year) with preseason body fat percentage (22.7 ± 5.3%), participated in the Yo-Yo Intermittent Recovery Test 2 (YYIR2) prior to their fall pre-season conditioning period. Body fat percentage was assessed pre and post-season using BodPod assessment. Zephyr Performance Systems were worn during home season games to quantify and record the athletes' physiological load, which was averaged over the season (AVEPL). Athletes completed a second YYIR2 at the conclusion of their post-season play and the change in the distance covered on this assessment from pre to post-season was recorded (ChangeDist). RESULTS: No differences were observed in YYIR2 or body fat percentage between pre and post-season. However, AVEPL was negatively correlated with pre to post-season change in distance covered (ChangeDist), r =-0.489, p =0.040. Linear regression analysis also revealed ChangeDist was inversely related to AVEPL (β =-0.448, p =0.048). When adjusted for age and pre to post-season change in body fat percentage (ChangeBF), AVEPL remained inversely related to ChangeDist (β =-0.446, p =0.037). CONCLUSIONS: Athletes with higher average physiological load across the season exhibited a decrease in performance on the post-season Yo-Yo Intermittent Recovery Test 2 when compared to pre-season, regardless of change in body fat percentage. Further research should be done to determine whether these results are due to a true decline in fitness levels or a decline in motivation to perform on the post-season assessment.
Arteriosclerosis, Thrombosis, and Vascular Biology, Jun 1, 2018
Objective-PAR2 (protease-activated receptor 2)-dependent signaling results in augmented inflammat... more Objective-PAR2 (protease-activated receptor 2)-dependent signaling results in augmented inflammation and has been implicated in the pathogenesis of several autoimmune conditions. The objective of this study was to determine the effect of PAR2 deficiency on the development of atherosclerosis. Approach and Results-PAR2 mRNA and protein expression is increased in human carotid artery and mouse aortic arch atheroma versus control carotid and aortic arch arteries, respectively. To determine the effect of PAR2 deficiency on atherosclerosis, male and female low-density lipoprotein receptor-deficient (Ldlr −/−) mice (8-12 weeks old) that were Par2 +/+ or Par2 −/− were fed a fat-and cholesterol-enriched diet for 12 or 24 weeks. PAR2 deficiency attenuated atherosclerosis in the aortic sinus and aortic root after 12 and 24 weeks. PAR2 deficiency did not alter total plasma cholesterol concentrations or lipoprotein distributions. Bone marrow transplantation showed that PAR2 on nonhematopoietic cells contributed to atherosclerosis. PAR2 deficiency significantly attenuated levels of the chemokines Ccl2 and Cxcl1 in the circulation and macrophage content in atherosclerotic lesions. Mechanistic studies using isolated primary vascular smooth muscle cells showed that PAR2 deficiency is associated with reduced Ccl2 and Cxcl1 mRNA expression and protein release into the supernatant resulting in less monocyte migration. Conclusions-Our results indicate that PAR2 deficiency is associated with attenuation of atherosclerosis and may reduce lesion progression by blunting Ccl2-and Cxcl1-induced monocyte infiltration. Visual Overview-An online visual overview is available for this article.
Carolina Digital Repository (University of North Carolina at Chapel Hill), 2017
In this longitudinal study we explored the relationships between plasma n-3 and n-6 polyunsaturat... more In this longitudinal study we explored the relationships between plasma n-3 and n-6 polyunsaturated fatty acids (PUFAs) and Δ5 and Δ6 desaturase activities (D5D and D6D, respectively) and fasting lipids in youth with type 1 diabetes (T1D). Methods-Incident cases of T1D in youth <20 years of age who were seen for a baseline study visit (N=914) and a 1-year follow-up visit (N=416) were included. Fasting blood samples were obtained at each visit and plasma phospholipid n-6 PUFAs were measured, which included linoleic acid (LA), dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA); n-3 PUFAs included αlinolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Estimated D5D and D6D were calculated as FA product-to-precursor ratios, where D5D= AA/DGLA and D6D = DGLA/LA. To examine the longitudinal relationships between long chain PUFAs, desaturase activities and fasting plasma lipids in youth with T1D mixed effects models were used for each individual PUFAs, D5D and D6D, adjusted for demographics, clinic site, diabetes duration, insulin regimen, insulin dose/kg, HbA1c, insulin sensitivity score, and body mass index with random effects to account for the repeated measurements. Findings-Favorable lipid associations were found between LA and low-density lipoprotein (LDL) cholesterol (β= −0.58, P<0.05); AA, plasma triglycerides (TG) (β= −0.04, P<0.05) and TG/ high-density lipoprotein (HDL)-C ratio (β= −0.04, P<0.05); and D5D, plasma TG (β= −0.2, P<0.05) and TG/HDL-cholesterol ratio (β= −0.23, P<0.05). Findings were mixed for the n-3 PUFAs and DGLA: ALA was positively associated with plasma TG (β= 0.33, P<0.05) and HDL cholesterol (β= 9.86, P<0.05); EPA was positively associated with total cholesterol (β= 8.17, P<0.05), LDL cholesterol (β=5.74, P<0.01) and HDL cholesterol (β= 2.27, P<0.01); and DGLA was positively associated with TG/HDL-cholesterol ratio (β= 0.05, P<0.05) Conclusion-Findings suggest that the most abundant PUFA, LA as well as its metabolic biproduct AA, may be important targets for CVD lipid risk factor reduction in youth with T1D.
Journal of Functional Morphology and Kinesiology, Sep 28, 2020
Body composition plays a key role in overall health and sports performance and its assessment is ... more Body composition plays a key role in overall health and sports performance and its assessment is an important part of many athletic programs. The purpose of this study was to describe longitudinal changes in body composition for collegiate female soccer players in order to provide data to inform future training and nutrition interventions for this population. A linear mixed-model (LMM) approach was used to analyze four years of pre-and post-season body composition data, including total mass, fat-free mass (FFM), fat mass, and body fat percentage (%BF) for 49 athletes. Athletes gained an average of 0.5 kg FFM during the season (p < 0.05) and increased total mass, FFM, fat mass, and %BF (2.5 kg, 1.1 kg, 1.7 kg, and 1.7%, respectively; p < 0.05) over four years. Freshmen experienced a 1.5 kg gain in total mass pre-to post-season (p < 0.05), while no changes in total mass or body composition were seen in other grade levels. Gains in %BF during the off season between Freshman and Sophomore years represented negative changes in body composition that should be addressed further. These results can help interdisciplinary athlete care teams optimize training programs in this population by understanding what changes are expected over multiple years. Normalizing these changes may also help the promotion of realistic body composition goals and the development of positive training and dietary habits.
Medicine and Science in Sports and Exercise, Jul 1, 2020
Journal of Immunology, Apr 1, 2010
Epigallocatechin-3-gallate (EGCG), a bioactive component of green tea, has been reported to exert... more Epigallocatechin-3-gallate (EGCG), a bioactive component of green tea, has been reported to exert anti-inflammatory effects in immune cells. EGCG has been shown to activate the metabolic regulator, AMP-activated protein kinase (AMPK). Mesangial cells from MRL/lpr lupus-like mice are hyper-responsive to immune stimulation and overproduce nitric oxide (NO) and other inflammatory mediators when stimulated. In our current studies, we sought to determine if EGCG would inhibit inflammation in AMPK deficient mesangial cells. Cultured mesangial cells from MRL/lpr mice were treated with siRNA for mouse Prkaa2-Design A, specific for AMP-activated protein kinase-alpha (AMPK-α) or siRNA negative control for mouse. After 48 hours, the cells were serum-starved for 2 hours, treated with 50 μM epigallocatechin-gallate (EGCG) for one hour, and stimulated with lipopolysaccharide (LPS)/interferon (IFN)-γ for 30 minutes. The addition of siRNA inhibited AMPK expression in mesangial cells. LPS/IFN-γ induced inflammatory mediator production (iNOS expression, supernatant NO, and interleukin-6) as expected. Interestingly, EGCG blocked inflammatory mediator production in the AMPK deficient cells suggesting EGCG inhibits inflammatory pathways independently of AMPK to decrease inflammatory mediatory production. Taken together, these studies show that EGCG attenuated inflammation in MRL/lpr mouse mesangial cells independent of AMPK.
Pediatric Hematology and Oncology, Nov 5, 2020
Historically, youth with sickle cell disease (SCD) were at risk for being underweight, but recent... more Historically, youth with sickle cell disease (SCD) were at risk for being underweight, but recent data suggests this population is replicating obesity trends of youth in the United States. The current observational study assessed the weight status and health behaviors of 44 adolescents and young adults with SCD via a self-report survey and chart review. Using height and weight data closest to survey completion date, 27% of participants were either overweight or obese. With respect to obesogenic risk behaviors, 77% ate fast food 1-3 times per week, 25% had no fruits/vegetables with any of their meals, 11% drank no water, and 57% watched 4 or more hours of television per day. Though more research is needed, this preliminary study adds to the SCD literature suggesting an emerging shift toward obesity in this population. As such, adolescents with SCD may benefit from interventions to decrease obesity risk factors as being overweight or obese has the potential to worsen SCD-related symptoms and complications.
The FASEB Journal, Apr 1, 2015
The Journal of Immunology
Epigallocatechin-3-gallate (EGCG), a bioactive component of green tea, has been reported to exert... more Epigallocatechin-3-gallate (EGCG), a bioactive component of green tea, has been reported to exert anti-inflammatory effects in immune cells. EGCG has been shown to activate the metabolic regulator, AMP-activated protein kinase (AMPK). Mesangial cells from MRL/lpr lupus-like mice are hyper-responsive to immune stimulation and overproduce nitric oxide (NO) and other inflammatory mediators when stimulated. In our current studies, we sought to determine if EGCG would inhibit inflammation in AMPK deficient mesangial cells. Cultured mesangial cells from MRL/lpr mice were treated with siRNA for mouse Prkaa2-Design A, specific for AMP-activated protein kinase-alpha (AMPK-α) or siRNA negative control for mouse. After 48 hours, the cells were serum-starved for 2 hours, treated with 50 μM epigallocatechin-gallate (EGCG) for one hour, and stimulated with lipopolysaccharide (LPS)/interferon (IFN)-γ for 30 minutes. The addition of siRNA inhibited AMPK expression in mesangial cells. LPS/IFN-γ indu...
Journal of Nutritional Science
Nutrients are an essential part of building and maintaining optimal health. Certain nutrient expo... more Nutrients are an essential part of building and maintaining optimal health. Certain nutrient exposure has been shown to be associated with many important health outcomes, although there is variability among studies. Despite the scientific efforts of many, it is unclear why some well-hypothesised nutrients lack sufficient evidence for clear association with health outcomes. One potential reason for conflicting results is that certain subgroups of patients benefit or are harmed more by adequate or inadequate exposure to certain nutrients. These subgroup-specific effects have historically not been studied, or if they are, it is often in a one-off type of approach where the investigator believes that a subgroup effect could exist based on limited previous data. In the era of big data, improvements can be made in efforts to generate new hypotheses for subgroups of patients and recommendations for precision nutrition can be made. In the present paper, we present a strategy for exploring s...
Diabetes management, 2019
Objective: Adolescents with type 1 diabetes (T1DM) must consider multiple factors in diet plannin... more Objective: Adolescents with type 1 diabetes (T1DM) must consider multiple factors in diet planning, including glycemic control and cardiovascular disease prevention, while ensuring adequate nutrition for growth. We examined diet composition, quality, and compliance for two dietary patterns-the traditional Dietary Approaches to Stop Hypertension (DASH) and a modified version of DASH in this population. Methods and Findings: Two feeding studies were conducted. First, adolescents with T1DM consumed their usual diet for 3 days followed by traditional DASH for 6 days. Next, DASH menus were adjusted to align with T1DM nutrition guidelines, and this modified DASH for Diabetes (DASH-D) was tested on a new group of adolescents with T1DM for 6 days, following 3 days of usual diet. Usual diet was measured via 24-hr dietary recalls. Dietary composition of DASH-D was compared to DASH and usual diet. Eighteen adolescents (9/group) participated. Compared to usual diet, intake of protein, fiber, fruit, vegetables, lean meats, and low-fat dairy were higher, while saturated fat and added sugar were lower, in DASH-D. Percent energy from fat was higher, and from carbohydrate lower, in DASH-D versus traditional DASH, with food group intake reflecting these patterns. Participants consumed 87% of foods provided for DASH, and 98% of foods provided for DASH-D. In both DASH iterations, participants met national guidelines for fat, saturated fat, fiber, and fruit/vegetable intake, while usual diet fell short *
Recent reports show that 5-amino-4-imidazole carboxamide riboside (AICAR), a pharmacological acti... more Recent reports show that 5-amino-4-imidazole carboxamide riboside (AICAR), a pharmacological activator of AMP-activated protein kinase (AMPK), inhibits the lipopolysaccharide (LPS)-induced production of proinflammatory cytokines. MRL/MPJ-Fas lpr (MRL/lpr) mice show an intrinsic decreased threshold for the production of inflammatory mediators when stimulated. In our current studies, we sought to determine if AMPK activation would inhibit inflammatory mediator production in stimulated kidney mesangial cells. Cultured mesangial cells from MRL/lpr mice were treated with AICAR and stimulated with LPS/interferon (IFN)-g. AICAR decreased dose-dependently inducible nitric oxide synthase (iNOS), cyclooxygenase-2 and interleukin-6 production in LPS/IFN-g-stimulated mesangial cells. Mechanistically, AICAR inhibited the LPS/IFN-g-stimulated PI3K/Akt signalling inflammatory cascade but did not affect LPS/IFN-g-mediated inhibitory kappa B phosphorylation or nuclear factor (NF)-kB (p65) nuclear translocation. Treatment with the adenosine kinase inhibitor 5Јiodotubercidin blocked the ability of AICAR to activate AMPK and prevented AICAR from inhibiting the LPS/IFN-g-stimulated PI3K/Akt pathway and attenuating iNOS expression. Taken together, these observations suggest that AICAR inhibits LPS/IFN-g-induced Akt phosphorylation through AMPK activation and may serve as a potential therapeutic target in inflammatory diseases.