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The role of arachidonic acid (AA) on the development of adipose tissue is still controversial since its metabolites, i.e., prostaglandins, can either stimulate or inhibit preadipocyte differentiation in vitro. In the present study, we evaluated the effects of early postnatal supplementation of AA on body weight and adipose tissue development in guinea pigs. Male newborn guinea pigs were fed for 21 days ( day 21) with diets (milk and pellet) supplemented (+AA) or not (−AA) with 1.2% (total fatty acids) AA. From day 21 to day 105 both groups were fed a chow diet. The 21-days-old +AA pups showed a twofold higher AA accretion in phospholipids associated with a two- to sixfold increase in several prostaglandins, such as 6-keto PGF1α(the stable hydrolysis product of PGI2), PGF2α, PGE2, and PGD2in adipose tissue, compared with the −AA group. No difference in fat pad and body weight, aP2, and leptin gene expression in adipose tissue, fasting plasma glucose, free-fatty acids, and triglyceride concentration was observed between groups at day 21 or day 105. These results show that dietary supplementation of AA during the suckling/weaning period increases prostaglandin levels in adipose tissue but does not influence early fat mass development in the guinea pig.

Recent data suggest that gut microbiota plays a significant role in fat accumulation. However, it is not clear whether gut microbiota is involved in the pathophysiology of type-2 diabetes. To address this issue, we modulated gut microbiota with two combinations of antibiotics in two different mouse models with insulin resistance. Treatment with norfloxacin and ampicillin for 2 weeks reduced the cecal bacterial DNA below the level of detection in ob/ob, diet-induced obese and insulin resistance (DIO) mice, and significantly improved fasting glycemia and oral glucose tolerance of the treated animals. The enhanced insulin sensitivity was independent of food intake or adiposity because pair-fed ob/ob mice were as glucose intolerant as the untreated ob/ob mice. The reduced liver triglycerides, increased liver glycogen and improved glucose tolerance in the treated mice indicate broad impacts on metabolism by gut decontamination. The treatment with non-absorbable antibiotics polymyxin B and neomycin significantly modified cecal microbiota profile in the DIO mice, and the modified intestinal microbiota was associated with a gradual reduction in glycemia during a washout period. In summary, modulation of gut microbiota ameliorated glucose intolerance in mice and altered the hormonal, inflammatory and metabolic status of the host.

International audience; Recent data suggest that the gut microbiota plays a significant role in fat accumulation. However, it is not clear whether gut microbiota is involved in the pathophysiology of type 2 diabetes. To assess this issue, we modulated gut microbiota via antibiotics administration in two different mouse models with insulin resistance. Results from dose-determination studies showed that a combination of norfloxacin and ampicillin, at a dose of 1 g/L, maximally suppressed the numbers of cecal aerobic and anaerobic bacteria in ob/ob mice. After a 2-wk intervention with the antibiotic combination, both ob/ob and diet-induced obese and insulin-resistant mice showed a significant improvement in fasting glycemia and oral glucose tolerance. The improved glycemic control was independent of food intake or adiposity because pair-fed ob/ob mice were as glucose intolerant as the control ob/ob mice. Reduced liver triglycerides and increased liver glycogen correlated with improved glucose tolerance in the treated mice. Concomitant reduction of plasma lipopolysaccharides and increase of adiponectin further supported the antidiabetic effects of the antibiotic treatment in ob/ob mice. In summary, modulation of gut microbiota ameliorated glucose tolerance of mice by altering the expression of hepatic and intestinal genes involved in inflammation and metabolism, and by changing the hormonal, inflammatory, and metabolic status of the host.

The objective of this study was to determine the contribution of mesothelial cells, present in human omental adipose tissue (OAT) but not in the subcutaneous depot (SAT), on the expression of inflammation-related factors.Comparison of the expression profiles of inflammation-related genes in mesothelial cells with those in the adipocyte-enriched (AEF) and stromal vascular fractions (SVF) and localization of interleukin-18 (IL-18) expression in adipose depots.Eleven obese Caucasian female subjects undergoing gastric bypass surgery (body mass index: 43.6+/-1.3 kg/m(2); age: 41.6+/-2.3 years).The expression profiles of cytokine and chemokine-related genes in mesothelial cells and in cell fractions prepared from OAT were assessed by the microarray technique. The differential expression of IL-18 was confirmed by real-time PCR and the protein was localized in adipose depots by immunohistochemistry.Microarray data analysis demonstrated that, of the 16 cytokine and chemokine-related genes that were upregulated in mesothelial cells compared with the AEF, IL-18 was the cytokine with the highest differential expression. IL-18 expression was similar in mesothelial cells and the SVF. In both SAT and OAT, IL-18 was immunolocalized in neutrophils and mast cells, but not in macrophages nor adipocytes. This cytokine was also detected in mesothelial cells in OAT. This additional source of expression may explain the higher IL-18 expression levels in OAT than SAT (+5.9-fold).By their capacity to express inflammatory-related factors, and in particular the proinflammatory cytokine IL-18 in OAT, mesothelial cells appear as a new player in the process of low-grade inflammation associated with obesity.

peer-reviewed Background Excessive maternal weight gain during pregnancy impacts on offspring health. This study focused on the timing of maternal gestational weight gain, using a porcine model with mothers of normal pre-pregnancy weight. Methods Trial design ensured the trajectory of maternal gestational weight gain differed across treatments in early, mid and late gestation. Diet composition did not differ. On day 25 gestation, sows were assigned to one of five treatments: Control sows received a standard gestation diet of 2.3 kg/day (30 MJ DE/day) from early to late gestation (day 25–110 gestation). E sows received 4.6 kg food/day in early gestation (day 25–50 gestation). M sows doubled their food intake in mid gestation (day 50–80 gestation). EM sows doubled their food intake during both early and mid gestation (day 25–80 gestation). L sows consumed 3.5 kg food/day in late gestation (day 80–110 gestation). Offspring body weight and food intake levels were measured from birth to adolescence. Markers of lipid metabolism, hypertrophy and inflammation were investigated in subcutaneous adipose tissue of adolescent offspring. Results The trajectory of gestational weight gain differed across treatments. However total gestational weight gain did not differ except for EM sows who were the heaviest and fattest mothers at parturition. Offspring birth weight did not differ across treatments. Subcutaneous adipose tissue from EM offspring differed significantly from controls, with elevated mRNA levels of lipogenic (CD36, ACACB and LPL), nutrient transporters (FABP4 and GLUT4), lipolysis (HSL and ATGL), adipocyte size (MEST) and inflammation (PAI-1) indicators. The subcutaneous adipose depot from L offspring exhibited elevated levels of CD36, ACACB, LPL, GLUT4 and FABP4 mRNA transcripts compared to control offspring. Conclusions Increasing gestational weight gain in early gestation had the greatest impact on offspring postnatal growth rate. Increasing maternal food allowance in late gestation appeared to shift the offspring adipocyte focus towards accumulation of fat. Mothers who gained the most weight during gestation (EM mothers) gave birth to offspring whose subcutaneous adipose tissue, at adolescence, appeared hyperactive compared to controls. This study concluded that mothers, who gained more than the recommended weight gain in mid and late gestation, put their offspring adipose tissue at risk of dysfunction. This research was funded by Teagasc, under the National Development Plan. LBMcN was in receipt of a Teagasc Walsh Fellowship. Nestle hosted LG on a sabbatical and funded the RT-PCR cost.