Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA.
Department of Medicine, New York University School of Medicine, New York, NY.
J Nutr. 2018 Apr 1;148(4):562-572. doi: 10.1093/jn/nxy011.
trans-10,cis-12 Conjugated linoleic acid (t10,c12-CLA) is a dietary supplement that promotes weight loss by increasing fat oxidation and energy expenditure. We previously reported that in the absence of t10,c12-CLA, mice forced to lose equivalent body weight by food restriction (FR) do not exhibit increases in fat oxidation or energy expenditure but have improved glucose metabolism, consistent with FR as a metabolically healthy weight-loss method.
Because diet is a primary determinant of gut bacterial populations, we hypothesized that the disparate metabolic effects accompanying weight loss from t10,c12-CLA or FR could be related to altered intestinal microbiota.
Ten-week-old male LDL receptor-deficient (Ldlr-/-) mice were fed a high-fat, high-sucrose diet (HFHS; 36% lard fat, 36.2% sucrose + 0.15% cholesterol) for 12 wk (baseline), then switched to the HFHS diet alone (obese control), HFHS + 1% c9,t11-CLA (obese fatty acid control), HFHS + 1% t10,c12-CLA (weight-loss-inducing fatty acid), or HFHS + FR (weight-loss control group with 75-85% ad libitum HFHS food intake) for a further 8 wk. Fecal microbial content, short-chain fatty acids (butyrate, acetate), tissue CLA concentrations, and intestinal nutrient transporter expression were quantified.
Mice fed t10,c12-CLA or assigned to FR lost 14.5% of baseline body weight. t10,c12-CLA-fed mice had elevated concentrations of fecal butyrate (2-fold) and plasma acetate (1.5-fold) compared with HFHS-fed controls. Fecal α diversity decreased by 7.6-14% in all groups. Butyrivibrio and Roseburia, butyrate-producing microbes, were enriched over time by t10,c12-CLA. By comparing with each control group, we also identified bacterial genera significantly enriched in the t10,c12-CLA recipients, including Lactobacillus, Actinobacteria, and the newly identified Ileibacterium valens of the Allobaculum genus, whereas other taxa were enriched by FR, including Clostridiales and Bacteroides.
Modalities resulting in equivalent weight loss but with divergent metabolic effects are associated with compositional differences in the mouse intestinal microbiota.
反式-10，顺式-12 共轭亚油酸（t10，c12-CLA）是一种膳食补充剂，通过增加脂肪氧化和能量消耗来促进体重减轻。我们之前报道过，在没有 t10，c12-CLA 的情况下，通过食物限制（FR）迫使体重减轻相等的小鼠不会增加脂肪氧化或能量消耗，但改善了葡萄糖代谢，这与 FR 作为一种代谢健康的减肥方法一致。
因为饮食是肠道细菌群体的主要决定因素，我们假设伴随 t10，c12-CLA 或 FR 减肥而来的不同代谢效应可能与肠道微生物群的改变有关。
10 周龄的 LDL 受体缺陷（Ldlr-/-）雄性小鼠喂食高脂肪、高蔗糖饮食（HFHS；36%猪油脂肪，36.2%蔗糖+0.15%胆固醇）12 周（基线），然后切换到仅 HFHS 饮食（肥胖对照组）、HFHS+1% c9，t11-CLA（肥胖脂肪酸对照组）、HFHS+1% t10，c12-CLA（诱导体重减轻的脂肪酸）或 HFHS+FR（75-85%随意 HFHS 食物摄入量的体重减轻对照组）进一步 8 周。定量粪便微生物含量、短链脂肪酸（丁酸盐、醋酸盐）、组织 CLA 浓度和肠道营养转运蛋白表达。
喂食 t10，c12-CLA 或分配给 FR 的小鼠体重减轻了基线体重的 14.5%。与 HFHS 喂养的对照组相比，t10，c12-CLA 喂养的小鼠粪便中丁酸盐（增加 2 倍）和血浆醋酸盐（增加 1.5 倍）浓度升高。所有组的粪便α多样性下降了 7.6-14%。随着时间的推移，丁酸盐产生菌 Butyrivibrio 和 Roseburia 通过 t10，c12-CLA 富集。通过与每个对照组进行比较，我们还在 t10，c12-CLA 接受者中鉴定出显著富集的细菌属，包括乳杆菌属、放线菌属和新鉴定的 Allobaculum 属的 Ileibacterium valens，而 FR 则富集了其他分类群，包括梭菌目和拟杆菌属。
导致等效体重减轻但具有不同代谢效应的方式与小鼠肠道微生物群的组成差异有关。
