Morbidly “Healthy” Obese Are Not Metabolically Healthy but Less Metabolically Imbalanced Than Those with Type 2 Diabetes or Dyslipidemia (original) (raw)
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Visceral Fat Adipokine Secretion Is Associated With Systemic Inflammation in Obese Humans
Diabetes, 2007
Although excess visceral fat is associated with noninfectious inflammation, it is not clear whether visceral fat is simply associated with or actually causes metabolic disease in humans. To evaluate the hypothesis that visceral fat promotes systemic inflammation by secreting inflammatory adipokines into the portal circulation that drains visceral fat, we determined adipokine arteriovenous concentration differences across visceral fat, by obtaining portal vein and radial artery blood samples, in 25 extremely obese subjects (mean ؎ SD BMI 54.7 ؎ 12.6 kg/m 2 ) during gastric bypass surgery at Barnes-Jewish Hospital in St. Louis, Missouri. Mean plasma interleukin (IL)-6 concentration was ϳ50% greater in the portal vein than in the radial artery in obese subjects (P ؍ 0.007). Portal vein IL-6 concentration correlated directly with systemic C-reactive protein concentrations (r ؍ 0.544, P ؍ 0.005). Mean plasma leptin concentration was ϳ20% lower in the portal vein than in the radial artery in obese subjects (P ؍ 0.0002). Plasma tumor necrosis factor-␣, resistin, macrophage chemoattractant protein-1, and adiponectin concentrations were similar in the portal vein and radial artery in obese subjects. These data suggest that visceral fat is an important site for IL-6 secretion and provide a potential mechanistic link between visceral fat and systemic inflammation in people with abdominal obesity. Diabetes 56:1010 -1013, 2007
Gastric bypass surgery reveals independency of obesity and diabetes melitus type 2
Background: Roux-en-Y gastric bypass surgery is widely applied to ameliorate morbid obesity, including diabetes in people with type 2 diabetes. The latter vanish a few days after surgery for many, but not in all patients before any weight reduction has occurred. The explanation for this change in metabolic status is poorly understood, but the observation may suggest that the fate obesity and diabetes is only partly linked after surgery. Methods: The trajectories of weight reduction measured as reduced body mass index (BMI) in 741obese subjects with and without diabetes were evaluated. Evaluation was performed on three groups: 1) subjects that were non-diabetic before and after surgery; 2) subjects that were diabetics before surgery but non-diabetics after surgery; and 3) subjects that were diabetics before surgery and remained diabetics after surgery. The diabetic state was established at HbA1c above 48 mmol/mol. Results: The trajectories differ significantly between groups and any sub-populations of groups, the latter identified by the distance between individual trajectories using a k-means procedure. The results suggest that different domains in the enormous genetic network governing basic metabolism are perturbed in obesity and diabetes, and in fact some of the patients are affected by two distinct diseases: obesity and diabetes mellitus type 2. Conclusion: Although RYGB "normalized" many glycaemic parameters in some of the diabetic subjects apparently converting to a non-diabetics state, other diabetic subjects stay diabetic in the context of the new gut anatomy after surgery. Thus, the obesity part of the glycaemic derangement may have been ameliorated, but some defects of the diabetic state had not.
Journal of Obesity & Metabolic Syndrome, 2020
Background: Obese adipose tissue secretes a variety of adipocytokines that act as metabolic regulators with complex mechanisms. Our objective was to compare serum concentration of a panel of adipocytokines between obese and non-obese individuals and identify any distinct patterns correlating with insulin sensitivity in obesity. Methods: We designed a cross-sectional study among obese (body mass index [BMI] ≥30 kg/m 2 , n=62) and non-obese (BMI <25 kg/m 2 , n=32) individuals to compare circulating levels of the adipokines, such as adiponectin and resistin in conjunction with the measurement of the levels of inflammatory cytokines including C-reactive protein (CRP), interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α using Luminex multiplex immunoassay with drop array technology. Correlations between circulating adipocytokine levels and those of multiple well-established markers of insulin resistance including homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of β-cell function (HOMA-β) and quantitative insulin sensitivity check index were also established. Results: CRP, IL-8, MCP-1, and TNF-α levels were higher in obese than non-obese individuals; the CRP and IL-8 differences were statistically significant. CRP correlated significantly with markers of insulin resistance (fasting plasma insulin, HOMA-IR, and QUICKI), and adiponectin correlated with HOMA-β in obese individuals. We divided the group of obese individuals on the basis of HOMA-IR levels into insulin-resistant (IR; HOMA-IR ≥2.5) and insulin-sensitive (IS; HOMA-IR <2.5) groups; and 43 out of 62 participants were IR despite comparable BMIs. An overall proinflammatory profile was compared between IR and IS obese, though the values were higher in IR obese but the difference was not significant. Conclusion: Obesity is associated with a general inflammatory milieu and a crosstalk between adipocytokines and insulin resistance is complex as well as multifactorial.
Obesity Surgery, 2012
Background Obesity is associated with a low-grade inflammatory state. A causal association between inflammation and atherosclerosis has been suggested. The aim of this study was to evaluate changes in the proinflammatory profile of morbidly obese patients after weight loss following bariatric surgery. Methods In this study, we measured levels of adiponectin, high-sensitivity C-reactive protein (hs-CRP), tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) and their relation to insulin resistance and lipid parameters in 60 morbidly obese women at baseline and 3, 6 and 12 months after gastric bypass. Results Twelve months after surgery, there was a significant increase in plasma levels of adiponectin (p<0.001) and highdensity lipoprotein cholesterol (p<0.01) and a significant decrease in levels of IL-6 (p<0.001), hs-CRP (p<0.001), cholesterol (p<0.001), triglycerides (p<0.001), low-density lipoprotein cholesterol (p<0.001), glucose (p<0.001), insulin (p<0.001) and homeostasis model assessment (HOMA; p<0.001). At 12 months, correlations were seen between IL-6 levels and the following: body mass index (BMI) (r00.53, p<0.001), insulin (r00.51, p<0.001) and HOMA (r00.55, p<0.001). Also, hs-CRP levels correlated with BMI (r00.40, p00. 004), triglycerides (r00.34, p00.017), insulin (r00.50, p00.001) and HOMA (r00.46, p00.002). Conclusions In patients with morbid obesity, significant weight loss is followed by a significant improvement in the inflammatory state, insulin sensitivity and lipid profile. A relationship exists between improved inflammatory profile and insulin sensitivity.
Insulin Resistance, Leptin and TNF-α System in Morbidly Obese Women after Gastric Bypass
Obesity Surgery, 2003
Obesity is a complex disease associated with insulin resistance. Leptin and the TNF-α system could be involved in the pathogenesis of obesity and insulin resistance. Gastric bypass (GBP) is a surgical treatment for morbidly obese patients. We conducted a study after GBP to analyze the pattern of variation of anthropometric and body composition variables, leptin and sTNFR1 and 2. Methods: 29 morbidly obese women were studied, at baseline and throughout 6 months after gastric bypass. Results: At baseline, the BMI was 49 ± 6 kg/m2 and patients showed a higher fasting insulin resistance index (FIRI), leptin, leptin/fat mass and sTNFR1 and 2 than did controls. 6 months after GBP, BMI was 35±4, and FIRI, leptin and leptin/fat mass decreased significantly in the first months and throughout the follow-up. sTNFR1 and 2 showed an initial increase, but at 6 months their concentrations were similar to baseline (2.6±0.8 vs 3.1±0.95 ng/ml, P < 0.05; 4.6±1.4 vs 7±2.5 ng/ml, P < 0.05). At baseline, there was no correlation between leptin and BMI and body composition variables but there was a correlation with fat mass (r=0.42, P=0.004) and sTNFR1 (r=0.58, P=0.001). At 6 months, there was a correlation between leptin and BMI (r=0.53, P=0.004) and sTNFR1 (r=0.46, P=0.013). Conclusions: Morbidly obese women after GBP became less insulin resistant with lower leptin concentrations, but showed an initial increase of sTNFR1 and 2. This pattern of variation of the leptin TNF-α axis suggests a disregulation of the system after dramatic weight loss and also that insulin and leptin up-regulate TNF-α production irrespective of insulin resistance status.
Nutrients, 2019
Bariatric surgery remains the most effective option for achieving important and sustained weight loss. We explored the effects of Roux-en-Y gastric bypass (RYGB) on the circulating levels of adiponectin, leptin, and the adiponectin/leptin (Adpn/Lep) ratio in patients with obesity and type 2 diabetes (T2D). Twenty-five T2D volunteers undergoing RYGB were included in the study, and further subclassified as patients that responded or not to RYBG, regarding remission of T2D. Anthropometric and biochemical variables were evaluated before and after RYGB. Obese patients with T2D exhibited an increase (p < 0.0001) in the Adpn/Lep ratio after RYGB. Changes in the Adpn/Lep ratio correlated better with changes in anthropometric data (p < 0.001) than with the variations of adiponectin or leptin alone. Multiple regression analysis revealed that the change in the Adpn/Lep ratio in patients with T2D was an independent predictor of the changes in body mass index (p < 0.001) and body fat pe...
Cytokine, 2018
Metabolically healthy obesity is characterized as a comorbidity-free obesity status, however the exact pathogenetic mechanisms implicated in its transition to unhealthy obesity have not yet been unveiled. Our aim was to investigate the effect of metabolic health on the proteomic profile both in serum and visceral fat of morbidly obese subjects. 28 patients undergoing bariatric surgery were prospectively enrolled. They were divided into two groups: metabolically healthy (MHO, n = 18) and unhealthy (MUO, n = 10) obese patients. 30 biomarkers were measured in serum and visceral adipose tissue with the use of targeted proteomic analysis (Luminex assays). TNF weak inducer of apoptosis (TWEAK) (p = 0.043), TNF related apoptosis inducing ligand (TRAIL) (p = 0.037), Growth differentiation factor-15 (GDF-15) (p = 0.04), Resistin (RETN) (p = 0.047), Matrix metalloproteinase-9 (MMP-9) (p = 0.011) and C-terminal telopeptide (ICTP) (p = 0.022) were up-regulated in the MUO group in the visceral white adipose tissue. Moreover, CC motif ligand-3 (CCL-3) (p = 0.056), Interleukin-20 (IL-20) (p = 0.04), Prokineticin-1 (PROK-1) (p = 0.028) and TWEAK (p = 0.016) were found to be suppressed in the serum of MHO group. Significant correlations between serum and adipose tissue levels of certain cytokines were also observed, while 16 biomarkers were associated with BMI. Our results indicate metabolic health substantially attenuates the expression of TWEAK, TRAIL, GDF-15, RETN, MMP-9 and ICTP expression locally, in the visceral white adipose tissue, and the expression of CCL-3, IL-20, PROK-1 and TWEAK in the peripheral blood. Intriguingly, different cytokines-except for TWEAK-are up-regulated in each site, suggesting that obesity is not a homogenous but a multi-dimensional disease.
Integrative Obesity and Diabetes, 2017
The increased prevalence of obesity worldwide is a serious problem as it invites several other metabolic chronic disorders including Diabetes mellitus, one of the major global pandemic now a days. Obesity raises the propensity of developing insulin resistance and type 2 diabetes mellitus (T2DM) by several folds. Adipose tissue derived increased amounts of non-esterified fatty acids, glycerol, hormones, proinflammatory cytokines and other factors are involved in the development of insulin resistance in obese individuals. When insulin resistance is accompanied by pancreatic islet β-cell dysfunction, glycemic control worsens resulting in diabetes. Abnormalities in β-cell function are therefore critical in defining the risk and development of type 2 diabetes. Although clinical studies aimed at reducing the deleterious effects of these conditions have been conducted or are undergoing trials, detailed exploration of the molecular and metabolic basis of the disease may guide us to new approaches to its prevention and treatment. Risk factors in obesity and T2DM There are multiple risk factors associated with obesity and diabetes mellitus which includes physical inactivity, sedentary lifestyle, family history, high risk ethnicity, cardiovascular disease (CVD), dyslipidemia, hypertension, sleep apnoea, renal disease, and others[14]. The gene polymorphisms in ADIPOQ (rs1501299 and rs17300539), LepR (rs1137101 and rs1045895), IRS2 (rs1805092), GRB14 (rs10195252 and rs3923113) and PPARG (rs1801282) have also been associated with overweight and obesity in uncontrolled T2DM [15]. Apart from the gene polymorphisms, population based long-term prospective and cross-sectional studies have identified many risk factors of T2DM as well as obesity, and some of these like altered blood levels of adipokines, chemokines, elevated circulating proinflammatory cytokines, vitamin