Increasing fat content from 20 to 45 wt% in a complex diet induces lower endotoxemia in parallel with an increased number of intestinal goblet cells in mice.

The impacts of high-fat diets (HFDs) on the onset of metabolic endotoxemia and low-grade inflammation are well established in rodent models. However, the dose-effect of dietary lipid intakes on these parameters is not known. We hypothesized that increasing dietary lipid amounts could be linked to parallel increases of endotoxemia, low-grade inflammation, and metabolic and intestinal alterations. Six-week-old male C57BL/6J mice were fed a low-fat diet (LFD, 2.6 wt% of lipids), a moderate HFD (mHFD, 22 wt% of lipids), or a very HFD (vHFD, 45 wt% of lipids) formulated mainly using chow ingredients and milk fat. After 12 weeks, white adipose tissues, liver, intestine, distal colon contents, and plasma were collected. Only vHFD mice significantly increased body weight and fat mass vs LFD mice. This was associated with increases of plasma concentrations of triglycerides, leptin and adiponectin, and liver lipids. No such differences were observed between LFD and mHFD mice. However, mHFD developed metabolic endotoxemia and inflammation, unlike vHFD mice. In turn, vHFD mice showed more goblet cells in all intestine segments vs both other groups and a decrease of Bacteroides-Prevotella in their microbiota vs LFD mice. Finally, mHFD mice colon exhibited a decrease in lactobacilli and in the levels of occludin phosphorylation. Altogether, using complex HFD, no associations were observed between dietary lipid amounts and the magnitude of endotoxemia, inflammation, and physiological alterations developed. These results reveal the impact of the diet composition on intestinal goblet cells and mucus coat, bringing new insights about further consequences on HFD-induced metabolic disorders.

Benoit B ，Laugerette F ，Plaisancié P ，Géloën A ，Bodennec J ，Estienne M ，Pineau G ，Bernalier-Donadille A ，Vidal H ，Michalski MC ... -  《-》

High-fat diet action on adiposity, inflammation, and insulin sensitivity depends on the control low-fat diet.

Animal studies using a high-fat diet (HFD) have studied the effects of lipid overconsumption by comparing a defined HFD either with a natural-ingredient chow diet or with a defined low-fat diet (LFD), despite the dramatic differences between these control diets. We hypothesized that these differences in the control diet could modify the conclusions regarding the effects that an increase of fat in the diet has on several metabolic parameters. For 11 weeks, C57bl6/J mice were fed a low-fat chow diet (8% energy from fat), a typical semisynthetic LFD (12%), or a semisynthetic HFD (sy-HF) (40%). Conclusions about the effect of sy-HF on body weight gain, subcutaneous adipose tissue, insulin sensitivity, and adipose tissue inflammation were modified according to the control LFD. Conversely, conclusions about epididymal and retroperitoneal adipose tissue; fat intake effects on liver and muscular lipids, cholesterol, free fatty acids, and markers of low-grade inflammation; and of adipose tissue macrophage infiltration were the same regardless of the use of low-fat chow diet or semisynthetic LFD. For some physiological outcomes, conflicting conclusions were even reached about the effects of increased fat intake according to the chosen low-fat control. Some deleterious effects of sy-HF may not be explained by lipid overconsumption but rather by the overall quality of ingredients in a semisynthetic diet. According to the control LFD chosen, conclusions on the lipid-related effects of HFDs must be formulated with great care because some end points are profoundly affected by the ingredient composition of the diet rather than by fat content.

Benoit B ，Plaisancié P ，Awada M ，Géloën A ，Estienne M ，Capel F ，Malpuech-Brugère C ，Debard C ，Pesenti S ，Morio B ，Vidal H ，Rieusset J ，Michalski MC ... -  《-》

Supplementation with Sodium Butyrate Modulates the Composition of the Gut Microbiota and Ameliorates High-Fat Diet-Induced Obesity in Mice.

Short-chain fatty acids (SCFAs) have been reported to ameliorate obesity. However, the underlying mechanisms require further investigation. The aim of this study was to determine the role of butyrate, an SCFA, in the regulation of obesity, low-grade chronic inflammation, and alterations of microbiota composition in mice. Male C57BL/6J mice, 4-5 wk of age, were divided into 3 groups (n = 8 mice/group): low-fat diet (LFD; 10% energy from fat), high-fat diet (HFD; 45% energy from fat), or high-fat diet plus sodium butyrate (HSB). HSB mice received sodium butyrate at a concentration of 0.1 M in drinking water for 12 wk. Measures of inflammation, obesity, and intestinal integrity were assessed. Serum lipopolysaccharide (LPS) concentrations were measured in the 3 groups. Fecal samples were collected for gut microbiota analysis. In HFD mice, body weight gain and hepatic triglyceride (TG), serum interleukin-6 (IL-6), and serum tumor necrosis factor (TNF)-α levels were 1-4 times higher than those in LFD mice (P < 0.05); they were 34-42% lower in HSB mice compared with HFD mice (P < 0.05). The HFD group had 28%-48% lower mRNA expression of both Tjp1 and Ocln in the ileum and colon compared with levels in LFD or HSB mice (P < 0.05), whereas there was no difference in expression levels between LFD and HSB mice. Furthermore, in HSB mice, serum LPS concentration was 53% lower compared with that in HFD mice but still 23% higher than that in LFD mice (P < 0.05). Results from principal component analysis showed that HSB and LFD mice had a similar gut microbiota structure, which was significantly different from that in HFD mice (P < 0.05). Sodium butyrate administration beneficially changed HFD-induced gut microbiota composition and improved intestinal barrier, leading to lower serum LPS concentrations. These changes may correspond with improvements in obesity-related lipid accumulation and low-grade chronic inflammation.

Fang W ，Xue H ，Chen X ，Chen K ，Ling W ... -  《-》

Dietary emulsifiers from milk and soybean differently impact adiposity and inflammation in association with modulation of colonic goblet cells in high-fat fed mice.

Enhanced adiposity and metabolic inflammation are major features of obesity that could be impacted by dietary emulsifiers. We investigated in high-fat fed mice the effects of using a new polar lipid (PL) emulsifier from milk (MPL) instead of soybean lecithin (soybean PL [SPL]) on adipose tissue and intestinal mucosa function. Four groups of C57BL6 mice received for 8 wks a low-fat (LF) diet or a high-fat diet devoid of PLs or an high-fat diet including MPL (high-fat-MPL) or SPL (high-fat-SPL). Compared with high-fat diet, high-fat-SPL diet increased white adipose tissue (WAT) mass (p < 0.05), with larger adipocytes (p < 0.05) and increased expression of tumor necrosis factor alpha, monochemoattractant protein-1, LPS-binding protein, and leptin (p < 0.05). This was not observed with high-fat-MPL diet despite similar dietary intakes and increased expression of fatty acid transport protein 4 and microsomal TG transfer protein, involved in lipid absorption, in upper intestine (p < 0.05). High-fat-MPL mice had a lower expression in WAT of cluster of differentiation 68, marker of macrophage infiltration, versus high-fat and high-fat-SPL mice (p < 0.05), and more goblet cells in the colon (p < 0.05). Unlike SPL, MPL in the high-fat diet did not induce WAT hypertrophy and inflammation but increased colonic goblet cells. This supports further clinical exploration of different sources of dietary emulsifiers in the frame of obesity outbreak.

Lecomte M ，Couëdelo L ，Meugnier E ，Plaisancié P ，Létisse M ，Benoit B ，Gabert L ，Penhoat A ，Durand A ，Pineau G ，Joffre F ，Géloën A ，Vaysse C ，Laugerette F ，Michalski MC ... -  《-》

Effects of high-fat diet on plasma lipids, adiposity, and inflammatory markers in ovariectomized C57BL/6 mice.

We hypothesized that a high-fat (HF) diet aggravates ovariectomy-related complications. To test this hypothesis, ovariectomized (OVX) mice were fed a HF diet, and we investigated the lipid metabolism, adipose tissue remodeling, adipokines, and inflammatory cytokines. To investigate the situation in a mouse model of ovariectomy, OVX and SHAM C57BL/6 mice fed a HF diet (60% fat) or standard chow (SC, 10% fat) were monitored for 18 wk. We evaluated daily food intake and weekly body weight. Mice were killed at 30 wk of age. Blood samples and adipose tissue were collected for biochemical, histologic, and molecular analysis. OVX groups showed atrophied uterus compared to the SHAM groups, ensuring the success of surgically induced menopause. Despite lower food intake, OVX-HF mice gained about 52% more weight and had heavier total body fats, especially in relation to ovarian fat pad (372%)-a visceral fat which is associated with increased pathogenicity in obesity, and showed larger adipocytes (30%) when compared to OVX-SC mice. Biochemical analysis showed that the OVX-HF mice had increased levels of serum total cholesterol (51%), greater serum triglycerides (158%), lower serum adiponectin (40%), and higher plasma leptin (323%) than OVX-SC mice. The obese group (OVX-HF) also had higher IL-6 levels than both SHAM-HF (241%) and OVX-SC mice (870%). OVX C57BL/6 mice fed HF diet had greater adipose fat pad, larger adipocytes, and increased inflammatory markers, reinforcing the idea that a HF diet aggravates the complications of ovariectomy-associated inflammation.

Ludgero-Correia A Jr ，Aguila MB ，Mandarim-de-Lacerda CA ，Faria TS ... -  《-》