Effect of Dietary Lipids on Endotoxemia Influences Postprandial Inflammatory Response (original) (raw)

The Importance of Food for Endotoxemia and an Inflammatory Response

International Journal of Molecular Sciences

Bacterial endotoxin is a potent inflammatory antigen abundant in the human intestine. Endotoxins circulate in the blood at low concentrations in all healthy individuals. Elevated levels of circulatory endotoxins may cause inflammation with the development of chronic disease, either affecting metabolism, neurological disease, or resistance to viral and bacterial infections. The most important endotoxin is LPS, being a superantigen. In this narrative review, the effect of various food components to postprandially elevate circulating LPS and inflammatory markers is described. There is evidence that the intake of food enriched in fat, in particular saturated fat, may elevate LPS and pro-inflammatory markers. This occurs in both normal-weight and obese subjects. In obese subjects, inflammatory markers are already elevated before meal consumption. The importance of food choice for endotoxemia and inflammatory response is discussed.

Dietary fat modifies the postprandial inflammatory state in subjects with metabolic syndrome: the LIPGENE study

Molecular Nutrition & Food Research, 2012

Scope: Our aim was to investigate whether the inflammatory state associated to metabolic syndrome (MetS) patients is affected by diets with different fat quality and quantity. Methods and results: Seventy-five subjects from LIPGENE cohort were included in this feeding trial and randomly assigned to one of four diets: high saturated fatty acids (HSFA); high monounsaturated fatty acids (HMUFA) and two low-fat, high complex carbohydrate (LFHCC) diets, supplemented with long-chain n-3 polyunsaturated fatty acids (LFHCC n-3) or placebo (LFHCC), for 12 weeks each. A postprandial fat challenge, reflecting the intervention dietary fat composition, was conducted post-intervention. The HMUFA diet significantly reduced postprandial nuclear transcription factor-kappaB (NF-kB) activity and the nuclear p65 protein levels relative to fasting values (p < 0.05). Furthermore, we observed a postprandial decrease in this protein with the HMUFA diet compared with the HSFA and LFHCC diets (p < 0.05). The postprandial response of inhibitory molecule from NF-kB mRNA levels increased with the HMUFA diet compared with the HSFA and LFHCC n-3 diets (p < 0.05). Postprandial tumor necrosis factor-␣ and Metalloproteinase 9 mRNA levels were also reduced after the HMUFA diet compared with the HSFA diet (p < 0.05). Conclusion: Our results indicate that the long-term consumption of a healthy diet model with HMUFA attenuates the postprandial inflammatory state associated with MetS.

Effects of dietary fat quality on metabolic endotoxaemia: a systematic review

British Journal of Nutrition, 2020

In this systematic review, we critically evaluated human clinical trials that assessed the effects of dietary fat quality on metabolic endotoxaemia. The studies were selected from three databases (PubMed, Scopus and Cochrane Library), and the keywords were defined according to the Medical Subject Headings indexing terminology. Two authors searched independently, according to the pre-defined selection criteria. Quality and risk assessment of bias for each selected study were also evaluated. The results of the included studies demonstrated associations between higher SFA intake and increased postprandial lipopolysaccharide (LPS) concentrations. On the other hand, after the consumption of PUFA, bloodstream LPS concentrations were lower. However, in none of the long-term studies, the consumption of dietary fats did not seem to exert effects on LPS concentration. Hence, SFA seem to act as a risk factor for transient increase in endotoxaemia, while PUFA demonstrated exerting a protective ...

Realistic Test-Meal Protocols Lead to Blunted Postprandial Lipemia but Similar Inflammatory Responses Compared with a Standard High-Fat Meal

Current developments in nutrition, 2017

Background: A substantial increase in triglycerides (TGs) after a meal is associated with an increased risk of cardiovascular disease. Most studies investigating the effects of a meal on TGs have not used meals that reflect typical consumption. Objective: The objective of this study was to compare the TG and inflammatory responses of trueto-life meals, containing moderate fat and energy contents, with a high-fat, high-energy, lowcarbohydrate meal (HFM) typically used to test TG responses. Methods: Nine healthy, insufficiently active men [mean 6 SD age: 25.1 6 6.7 y; body mass index (in kg/m 2): 25.8 6 7.0; ,150 min moderate-to vigorous-intensity physical activity/wk] completed 3 meal trials in random order: an HFM (17 kcal/kg, 60% fat), a moderate-fat meal (MFM; 8.5 kcal/kg, 30% fat), and a biphasic meal (BPM), in which participants consumed the full MFM at baseline and 3 h postmeal. Blood samples were collected via an indwelling catheter at baseline and hourly for 6 h. Results: Peak blood TGs were significantly greater (P = 0.003) after the HFM (285.2 6 169.7 mg/dL) than after the MFM (156.0 6 98.7 mg/dL), but the BPM (198.3 6 182.8 mg/dL) was not significantly different from the HFM (P = 0.06) or the MFM (P = 0.99). Total area under the curve for TGs was greater after the HFM (1348.8 6 783.7 mg/dL 3 6 h) than after the MFM (765.8 6 486.8 mg/dL 3 6 h; P = 0.0005) and the BPM (951.8 6 787.7 mg/dL 3 6 h; P = 0.03), although the MFM and BPM were not significantly different (P = 0.72). There was a significant time-by-meal interaction for interferon g, but not for interleukins 6, 8, or 10. Conclusion: These findings in insufficiently active, healthy young men suggest that the large TG response after HFMs in previous studies may not reflect the metabolic state of many individuals in

Postprandial cell inflammatory response to a standardised fatty meal in subjects at different degree of cardiovascular risk

Thrombosis and Haemostasis, 2012

SummaryA fatty meal may represent a challenge of in vivo acute inflammatory reaction. We evaluated the acute effects of a standardised fatty meal administration on leukocytes and platelets and on their interactions on 61 subjects at different degree of cardiovascular risk, without any clinical event. Before and 2 hours after a fatty meal, blood cells were counted and markers of leukocyte (intracellular myeloperoxidase [MPO] and Mac-1) and platelet (P-selectin and microparticles) activation and mixed platelet-leukocyte conjugates measured by flow-cytometry. After the fatty meal, both white blood cell and platelet count significantly increased, more markedly in subjects with lower cardiovascular risk score. Mac-1 expression too increased (from 32.2 ± 27.2% to 45.6 ± 29.0%, p=0.0016), while MPO decreased (from 83.1 ± 16.3% to 64.5 ± 23.1%, p<0.0001). A trend for increased platelet activation and interaction with leukocytes was also observed. Women were more markedly susceptible to f...

In vitro Modulation of the LPS-Induced Proinflammatory Profile of Hepatocytes and Macrophages- Approaches for Intervention in Obesity?

Frontiers in Cell and Developmental Biology, 2016

Low grade endotoxemia is a feature of obesity which is linked to development of steatohepatitis in non-alcoholic fatty liver disease. In this study, macrophages (J774) and hepatocytes (HepG2) were stimulated with lipopolysaccharide (LPS) from E. coli 0111: B4 and analyzed for modulation of this response when preconditioned or stimulated subsequent to LPS, with different doses of Vitamin D 3 or docosahexaenoic acid (DHA) over a time period of 1 and 5 days. Pro-inflammatory TNFα and pro-fibrotic TGFβ released into the supernatants were measured by ELISA; qPCR was performed for Srebp-1c and PPARα mRNA (genes for products involved in fatty acid synthesis and catabolism, respectively). Vitamin D 3 and DHA exerted a consistent, dose dependent anti-inflammatory effect, and increased PPARα relative to Srebp-1c in both cell types. By contrast, addition of free fatty acids (FFA, oleic acid/palmitic acid 2:1) caused aggravation of LPS-induced inflammatory reaction and an increase of Srebp-1c relative to PPARα. Our results argue in favor of dietary supplementation of Vitamin D 3 or DHA (and avoidance of monounsaturated/saturated fatty acids) to alleviate development of fatty liver disease.

Effect of the fat composition of a single meal on the composition and cytotoxic potencies of lipolytically-releasable free fatty acids in postprandial plasma

Atherosclerosis, 1998

Ingestion of a meal increases plasma levels of triglyceride (TG)-rich lipoproteins through the secretion of intestine-derived chylomcirons and liver-derived very low density lipoproteins (VLDL). We have determined the effects of the fat composition of a single meal on the composition of TG in TG-rich lipoproteins (VLDL + chylomicrons) and circulating and lipolytically-releasable free fatty acids (FFA) in postprandial (PP) plasma and on the cytotoxic potencies of the lipolytically-released FFA to cultured arterial wall cells. PP lipemia was induced by feeding fasted normolipidemic human subjects with a meal rich in saturated fat (SF) and another meal rich in polyunsaturated fat (PUF), or vice versa; each meal provided 65% of energy as fat, and polyunsaturated to saturated fatty acid ratios (P/S) of the SF and PUF in the meals were 0.40 and 2.49, respectively. The mean P/S of TG in TG-rich lipoproteins (1.43) and circulating FFA (1.46) in 4 h PP plasma of PUF were significantly higher than those in PP plasma of SF (0.44 and 0.59, respectively) in fasting plasma (0.52 and 0.53, respectively). In vitro lipolysis of fasting and PP serum by purified bovine milk lipoprotein lipase (LpL) resulted in a marked (8.8 -12.3-fold) increase in the serum FFA level. The P/S of serum FFA in postlipolysis fasting and PP serum were consistently higher than that of FFA or that of TG associated with TG-rich lipoproteins in prelipolysis fasting and PP serum, indicating that polyunsaturated TG in VLDL and/or chylomicrons is more susceptible than saturated TG to lipolysis. When postlipolysis serum was interacted with cultured endothelial cells and mouse peritoneal macrophages (MPM), the lipolytically-released FFA in PP serum of SF and PUF disrupted the barrier function of endothelial cells and were cytotocxic to cultured MPM; FFA in postlipolysis fasting serum was not cytotoxic. FFA in postlipolysis PP serum of PUF were consistently more potent than that in postlipolysis PP serum of SF. Further study showed that all long-chain monounsaturated FFA and polyunsaturated FFA, but not saturated FFA, incorporated into lipoproteins (LDL) were cytotoxic to cultured MPM. In conclusion, despite the generally well-accepted belief that SF is more atherogenic than PUF, the present study provides in vitro evidence that the lipolytic remnant products of TG-rich lipoproteins produced after a meal rich in PUF are more injurious to arterial wall cells than those produced after a meal rich in SF.

Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemia

British Journal of Nutrition, 2012

Lipopolysaccharide (LPS) may play an important role in chronic diseases through the activation of inflammatory responses. The type of diet consumed is of major concern for the prevention and treatment of these diseases. Evidence from animal and human studies has shown that LPS can diffuse from the gut to the circulatory system in response to the intake of high amounts of fat. The method by which LPS move into the circulatory system is either through direct diffusion due to intestinal paracellular permeability or through absorption by enterocytes during chylomicron secretion. Considering the impact of metabolic diseases on public health and the association between these diseases and the levels of LPS in the circulatory system, this review will mainly discuss the current knowledge about high-fat diets and subclinical inflammation. It will also describe the new evidence that correlates gut microbiota, intestinal permeability and alkaline phosphatase activity with increased blood LPS le...

Effects of dietary fat modification on oxidative stress and inflammatory markers in the LIPGENE study

British Journal of …, 2010

Subjects with the metabolic syndrome (MetS) have enhanced oxidative stress and inflammation. Dietary fat quality has been proposed to be implicated in these conditions. We investigated the impact of four diets distinct in fat quantity and quality on 8-iso-PGF 2a (a major F 2 -isoprostane and oxidative stress indicator), 15-keto-13,14-dihydro-PGF 2a (15-keto-dihydro-PGF 2a , a major PGF 2a metabolite and marker of cyclooxygenasemediated inflammation) and C-reactive protein (CRP). In a 12-week parallel multicentre dietary intervention study (LIPGENE), 417 volunteers with the MetS were randomly assigned to one of the four diets: two high-fat diets (38 % energy (%E)) rich in SFA or MUFA and two low-fat high-complex carbohydrate diets (28 %E) with (LFHCC n-3) or without (LFHCC) 1·24 g/d of very long chain n-3 fatty acid supplementation. Urinary levels of 8-iso-PGF 2a and 15-keto-dihydro-PGF 2a were determined by RIA and adjusted for urinary creatinine levels. Serum concentration of CRP was measured by ELISA. Neither concentrations of 8-iso-PGF 2a and 15-keto-dihydro-PGF 2a nor those of CRP differed between diet groups at baseline (P.0·07) or at the end of the study (P. 0·44). Also, no differences in changes of the markers were observed between the diet groups (8-iso-PGF 2a , P¼ 0·83; 15-keto-dihydro-PGF 2a , P¼0·45; and CRP, P¼ 0·97). In conclusion, a 12-week dietary fat modification did not affect the investigated markers of oxidative stress and inflammation among subjects with the MetS in the LIPGENE study.