Rice bran prevents high-fat diet-induced inflammation and macrophage content in adipose tissue.

BACKGROUND: The inflammatory process associated with obesity mainly arises from white adipose tissue (WAT) alterations. In the last few years, nutritional-based strategies have been positioned as promising alternatives to pharmacological approaches against these pathologies. Our aim was to determine the potential of a rice bran enzymatic extract (RBEE)-supplemented diet in the prevention of metabolic, biochemical and functional adipose tissue and macrophage changes associated with a diet-induced obesity (DIO) in mice. METHODS: C57BL/6J mice were fed high-fat diet (HF), 1 and 5 % RBEE-supplemented high-fat diet (HF1 % and HF5 %, respectively) and standard diet as control. Serum cardiometabolic parameters, adipocytes size and mRNA expression of pro-inflammatory biomarkers and macrophage polarization-related genes from WAT and liver were evaluated. RESULTS: RBEE administration significantly decreased insulin resistance in obese mice. Serum triglycerides, total cholesterol, glucose, insulin, adiponectin and nitrites from treated mice were partially restored, mainly by 1 % RBEE-enriched diet. The incremented adipocytes size observed in HF group was reduced by RBEE treatment, being 1 % more effective than 5 % RBEE. Pro-inflammatory biomarkers in WAT such as IL-6 and IL-1ß were significantly decreased in RBEE-treated mice. Adiponectin, PPARγ, TNF-α, Emr1 or M1/M2 levels were significantly restored in WAT from HF1 % compared to HF mice. CONCLUSIONS: RBEE-supplemented diet attenuated insulin resistance, dyslipidemia and morphological and functional alterations of adipose tissue in DIO mice. These benefits were accompanied by a modulating effect in adipocytes secretion and some biomarkers associated with macrophage polarization. Therefore, RBEE may be considered an alternative nutritional complement over metabolic syndrome and its complications.

The ZONE Diet and Metabolic Control in Type 2 Diabetes.

Obesity is associated with chronic inflammation of the adipose tissue, which contributes to obesity-associated complications such as insulin resistance and type 2 diabetes. The increased inflammatory response seems to be directly related to modern nutrition, particularly aspects of fat quality and macronutrient composition. We have recently published an observational study investigating the practicability and effects of a combined dietary intervention with increased relative protein content and low-glycemic-index carbohydrates, supplemented with omega-3 polyunsaturated fatty acids (PUFAs), on metabolic control and inflammatory parameters in real-life situations in patients with type 2 diabetes. The primary efficacy parameter was the change in HbA1c, and secondary parameters included change in systemic inflammation (measured by ultrasensitive C-reactive protein), body weight, waist circumference, fat mass, and homeostasis model assessment-insulin resistance. Counseling a protein-enriched and low-glycemic-index diet supplemented with long-chain omega-3 PUFAs in a real-life clinical setting improved glycemic control, waist circumference, and silent inflammation in overweight or obese patients with type 2 diabetes.

A protein-enriched low glycemic index diet with omega-3 polyunsaturated fatty acid supplementation exerts beneficial effects on metabolic control in type 2 diabetes.

AIMS: The current study aims to investigate practicability and effects of a combined dietary intervention with increased relative protein content supplemented with omega-3 polyunsaturated fatty acids (PUFA) on metabolic control and inflammatory parameters in a real life situation in type 2 diabetes patients. METHODS: In this observational study we advised thirty mostly obese patients with type 2 diabetes to follow a protein-enriched diet with carbohydrates of low glycemic index (low GI) and moderate fat reduction supplemented with omega-3 PUFA for 24 weeks. Primary efficacy parameter was the change in HbA1c; secondary parameters included changes in systemic inflammation (measured by ultrasensitive C-reactive protein, usCRP), body weight, waist circumference, fat mass. The study is registered at clinicaltrials.gov (NCT01474603). RESULTS: The dietary intervention significantly reduced the primary efficacy variable HbA1c from a baseline value of 63±11mmol/mol to 59±14mmol/mol (P=0.033) and 56±12mmol/mol (P=0.001) after 12 and 24 weeks, respectively. In addition, usCRP decreased significantly at 24 weeks (P=0.039). Waist circumference, an important indicator for cardiometabolic-risk and silent inflammation, decreased from baseline 116.0±14.1cm to 114.9±13.5cm (P=0.019), 114.0±14.4cm (P=0.001), and 112.7±13.4cm (P=0.049), after 3, 12 and 24 weeks, respectively. CONCLUSION: Counseling a protein enriched and low glycemic index diet supplemented with long-chain omega-3 PUFA in a real-life clinical setting improves glycemic control and also reduces waist circumference and silent inflammation in overweight or obese patients with type 2 diabetes.

Treatment with n-3 polyunsaturated fatty acids overcomes the inverse association of vitamin D deficiency with inflammation in severely obese patients: a randomized controlled trial.

UNLABELLED: Obesity affects the vitamin D status in humans. Vitamin D and long-chain n-3 polyunsaturated fatty acids (PUFA) provide benefit for the prevention of fractures and cardiovascular events, respectively, and both are involved in controlling inflammatory and immune responses. However, published epidemiological data suggest a potential interference of n-3 PUFA supplementation with vitamin D status. Therefore, we aimed to investigate in a randomized controlled clinical trial whether treatment with long chain n-3 PUFA affects vitamin D status in severely obese patients and potential interrelations of vitamin D and PUFA treatment with inflammatory parameters. Fifty-four severely obese (BMI ≥ 40 kg/m2) non-diabetic patients were treated for eight weeks with either 3.36 g/d EPA and DHA or the same amount of butter fat as control. Changes in serum 25-hydroxy-vitamin D [25(OH)D] concentrations, plasma fatty acid profiles and circulating inflammatory marker concentrations from baseline to end of treatment were assessed. At baseline 43/54 patients were vitamin D deficient (serum 25(OH)D concentration <50 nmol/l). Treatment with n-3 PUFA did not affect vitamin D status (P = 0.91). Serum 25(OH)D concentration correlated negatively with both IL-6 (P = 0.02) and hsCRP serum concentration (P = 0.03) at baseline. Strikingly, the negative correlations of 25(OH)D with IL-6 and hsCRP were lost after n-3 PUFA treatment. In conclusion, vitamin D status of severely obese patients remained unaffected by n-3 PUFA treatment. However, abrogation of the inverse association of 25(OH)D concentration with inflammatory markers indicated that n-3 PUFA treatment could compensate for some detrimental consequences of vitamin D deficiency. TRIAL REGISTRATION: ClinicalTrials.gov NCT00760760.

Long-chain n-3 PUFAs reduce adipose tissue and systemic inflammation in severely obese nondiabetic patients: a randomized controlled trial.

BACKGROUND: Chronic adipose tissue inflammation is a hallmark of obesity, triggering the development of associated pathologies, particularly type 2 diabetes. Long-chain n-3 PUFAs reduce cardiovascular events and exert well-established antiinflammatory effects, but their effects on human adipose tissue inflammation are unknown. OBJECTIVE: We investigated whether n-3 PUFAs reduce adipose tissue inflammation in severely obese nondiabetic patients. DESIGN: We treated 55 severely obese nondiabetic patients, scheduled to undergo elective bariatric surgery, with 3.36 g long-chain n-3 PUFAs/d (EPA, DHA) or an equivalent amount of butterfat as control, for 8 wk, in a randomized open-label controlled clinical trial. The primary efficacy measure was inflammatory gene expression in visceral and subcutaneous adipose tissue samples (subcutaneous adipose tissue and visceral adipose tissue), collected during surgery after the intervention. Secondary efficacy variables were adipose tissue production of antiinflammatory n-3 PUFA-derived eicosanoids, plasma concentrations of inflammatory markers, metabolic control, and the effect of the Pro12Ala PPARG polymorphism on the treatment response. RESULTS: Treatment with n-3 PUFAs, which was well tolerated, decreased the gene expression of most analyzed inflammatory genes in subcutaneous adipose tissue (P < 0.05) and increased production of antiinflammatory eicosanoids in visceral adipose tissue and subcutaneous adipose tissue (P < 0.05). In comparison with control subjects who received butterfat, circulating interleukin-6 and triglyceride concentrations decreased significantly in the n-3 PUFA group (P = 0.04 and P = 0.03, respectively). The Pro12Ala polymorphism affected the serum cholesterol response to n-3 PUFA treatment. CONCLUSIONS: Treatment with long-chain n-3 PUFAs favorably modulated adipose tissue and systemic inflammation in severely obese nondiabetic patients and improved lipid metabolism. These effects may be beneficial in the long-term treatment of obesity. This trial was registered at clinicaltrials.gov as NCT00760760.

Liver X receptors regulate adrenal steroidogenesis and hypothalamic-pituitary-adrenal feedback.

The nuclear hormone receptors liver X receptor alpha (LXRalpha) (NR1H3) and LXRbeta (NR1H2) are established regulators of cholesterol, lipid, and glucose metabolism and are attractive drug targets for the treatment of diabetes and cardiovascular disease. Adrenal steroid hormones including glucocorticoids and mineralocorticoids are known to interfere with glucose metabolism, insulin signaling, and blood pressure regulation. Here we present genome-wide expression profiles of LXR-responsive genes in both the adrenal and the pituitary gland. LXR activation in cultured adrenal cells inhibited expression of multiple steroidogenic genes and consequently decreased adrenal steroid hormone production. In addition, LXR agonist treatment elevated ACTH mRNA expression and hormone secretion from pituitary cells both in vitro and in vivo. Reduced expression of the glucocortioid-activating enzyme 11beta-hydroxysteroid dehydrogenase 1 in pituitary cells upon LXR activation suggests blunting of the negative feedback of glucocorticoids by LXRs. In conclusion, LXRs independently interfere with the hypothalamic-pituitary-adrenal axis regulation at the level of the pituitary and the adrenal gland.

Suppression of T cell signaling by polyunsaturated fatty acids: selectivity in inhibition of mitogen-activated protein kinase and nuclear factor activation.

Polyunsaturated fatty acids (PUFAs) are known to suppress inflammatory and autoimmune responses and, therefore, clinical applications of PUFAs as immunomodulatory substances are extensively studied. PUFAs are known to inhibit T cell responses, but with respect to TCR/CD3-mediated signal transduction only a block in CD3-induced phospholipase Cgamma1/calcium signaling has been shown so far. In this study, we investigated PUFA-mediated changes in downstream T cell signal transduction. We show that among the mitogen-activated protein kinase families activation of c-Jun NH(2)-terminal kinase, but not phosphorylation of extracellular signal-regulated kinase-1/-2 or p38 is inhibited. CD3/CD28-induced activity of NF-AT was markedly reduced by PUFA treatment, while activation of other nuclear receptors (AP-1 and NF-kappaB) remained unaltered. Furthermore, IL-2 promoter activity, IL-2 and IL-13 mRNA levels, IL-2 secretion, and IL-2R alpha-chain expression were significantly diminished by PUFA treatment, whereas the expression of IFN-gamma, IL-4, IL-10, and CD69 remained essentially unaffected by PUFAs. In conclusion, PUFA treatment of T cells inhibits selectively c-Jun NH(2)-terminal kinase and NF-AT activation, resulting in diminished production of IL-2 and IL-13.

Immunomodulation by polyunsaturated fatty acids: mechanisms and effects.

Polyunsaturated fatty acids (PUFAs) modulate immune responses, thereby exerting beneficial effects in a variety of inflammatory disorders. PUFAs of the n-3 series that are found in marine fish oils are particularly effective. A variety of molecular mechanisms have been found to explain how PUFAs could interfere with immune cell function. PUFAs alter eicosanoid (prostaglandin, leukotriene) synthesis, orphan nuclear receptor activation (e.g. peroxisome proliferator-activated receptors, liver X receptors) and T lymphocyte signaling by changing the molecular composition of special signaling platforms called lipid rafts. This review discusses these mechanisms in detail with respect to their probable relevance in vivo. In addition, the effects of PUFAs on the immune system in general are summarized, as are clinical effects in rheumatoid arthritis, inflammatory bowel disease and sepsis.