Branched-chain amino acid supplementation drives dynamic changes in gut microbiota without impairing glucose and lipid homeostasis at the different stages of insulin resistance in mice on a high-fat diet.

The potential role of dietary branched-chain amino acids on circulating branched-chain amino acid levels and their relationship with metabolic health are complex, and the literature is inconsistent. We aimed to explore the dynamic effects of branched-chain amino acid supplementation on glucose and lipid homeostasis at different stages of insulin resistance in high-fat diet-fed mice. Male C57BL/6J mice were fed with a normal chow diet, high-fat diet, or high-fat diet supplemented with 100% branched-chain amino acids for 12 or 24 wk. Metabolic parameters and gut microbiota profiling were performed at these two time points. High-fat diet feeding caused varying degrees of branched-chain amino acid metabolic disorders in two different stages of insulin resistance. Supplementing with branched-chain amino acids further exacerbated branched-chain amino acid accumulation in the early stage of insulin resistance (12 wk), while adding branched-chain amino acids did not further elevate branched-chain amino acid levels in the hyperglycemia and hyperinsulinemia stage (24 wk). Compared with the high-fat diet group, branched-chain amino acid supplementation did not affect body weight; liver total cholesterol and triacylglycerol levels; and serum glucose, insulin, total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels as well as glucose tolerance at these two time points but triggered dynamic changes in the gut bacterial diversity and gut microbiota composition and abundance, especially in the genus associated with obesity and related metabolic disorders. Dietary branched-chain amino acid supplementation drives dynamic changes in circulating branched-chain amino acid levels and gut microbiome without subsequent effects on glucose and lipid homeostasis in high-fat diet-induced obese mice within the parameters of our study.

Liu R ，Yang Y ，Shi G ，Zhang L ... -  《-》

BCAA Supplementation in Mice with Diet-induced Obesity Alters the Metabolome Without Impairing Glucose Homeostasis.

Circulating branched chain amino acid (BCAA) levels are elevated in obese humans and genetically obese rodents. However, the relationship of BCAAs to insulin resistance in diet-induced obese mice, a commonly used model to study glucose homeostasis, is still ill-defined. Here we examined how high-fat high-sucrose (HFHS) or high-fat diet (HFD) feeding, with or without BCAA supplementation in water, alters the metabolome in serum/plasma and tissues in mice and whether raising circulating BCAA levels worsens insulin resistance and glucose intolerance. Neither HFHS nor HFD feeding raised circulating BCAA levels in insulin-resistant diet-induced obese mice. BCAA supplementation raised circulating BCAA and branched-chain α-keto acid levels and C5-OH/C3-DC acylcarnitines (AC) in muscle from mice fed an HFHS diet or HFD, but did not worsen insulin resistance. A set of short- and long-chain acyl CoAs were elevated by diet alone in muscle, liver, and white adipose tissue (WAT), but not increased further by BCAA supplementation. HFD feeding reduced valine and leucine oxidation in WAT but not in muscle. BCAA supplementation markedly increased valine oxidation in muscle from HFD-fed mice, while leucine oxidation was unaffected by diet or BCAA treatment. Here we establish an extensive metabolome database showing tissue-specific changes in mice on 2 different HFDs, with or without BCAA supplementation. We conclude that mildly elevating circulating BCAAs and a subset of ACs by BCAA supplementation does not worsen insulin resistance or glucose tolerance in mice. This work highlights major differences in the effects of BCAAs on glucose homeostasis in diet-induced obese mice versus data reported in obese rats and in humans.

Lee J ，Vijayakumar A ，White PJ ，Xu Y ，Ilkayeva O ，Lynch CJ ，Newgard CB ，Kahn BB ... -  《-》

Green Tea Polyphenols Modulate Colonic Microbiota Diversity and Lipid Metabolism in High-Fat Diet Treated HFA Mice.

There is an increasing interest in the effect of dietary polyphenols on the intestinal microbiota and the possible associations between this effect and the development of obesity. However, limited information is available on how these polyphenols affect the gut microbiota and lipid metabolism. The co-action of a high-fat diet (HFD) and tea polyphenol (TP) on gut microbiota and lipid metabolism using a human flora-associated (HFA) C57BL/6J mice model is studied. TP reduced serum total cholesterol, triglyceride, low density lipoprotein, glucose (GLU) and insulin (INS) levels of HFD mice in a dose-dependent manner (P < 0.01). TP also significantly increased acetic acid and butyric acid levels in HFA mice. 16S rRNA V3 region Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (PCR-DGGE) profiles showed that HFD mice had significantly reduced microbial diversity. This reduction could be alleviated by TP, with a significant increase in the richness and diversity of colonic microbiota in the high-fat diet with 0.2% TP (TPM) and high-fat diet with 0.05% TP (TPL) groups (P < 0.05). 454 pyrosequencing analysis showed that the HFD group had a significant increase in the Bacteroidetes to Firmicutes (F/B) ratio (P < 0.001), which could effectively be reversed by TP. The results showed that the changes in composition and diversity of colonic microbiota by TP administration suppressed the host body weight and blood lipid increase in high-fat diet HFA mice. A high fat diet significantly impacted gut microbiota composition and lipid metabolism in human flora-associated mice, which were largely ameliorated by tea polyphenol (TP). Therefore, TPs may be effectively used in controlling or treating obesity, hyperlipidemia and other related metabolic diseases.

Wang L ，Zeng B ，Liu Z ，Liao Z ，Zhong Q ，Gu L ，Wei H ，Fang X ... -  《-》

Dietary Folic Acid Supplementation Inhibits HighFat DietInduced Body Weight Gain through Gut Microbiota-Associated Branched-Chain Amino Acids and Mitochondria in Mice.

Han W ，Li M ，Yang M ，Chen S ，Lu Y ，Tang T ，Wang R ，Zhang C ，Qi K ... -  《-》

[Heat-inactivated Streptococcus thermophilus MN002 alleviate lipid metabolism of high fat diet-fed induced obese mice through modulating gut microbiota structure and bile acids].

Zhao J ，Luo Y ，Li Y ，Cheng R ，Shen X ，Chen J ，Kang X ，Li Z ，He F ... -  《-》