Yogurt Supplementation Attenuated Insulin Resistance in Obese Mice by Reducing Systemic Markers of Metabolic Endotoxemia and Inflammation

Abstract

Abstract Objectives To understand the mechanisms by which yogurt attenuates insulin resistance and chronic inflammation in a diet-induced obesity model. Methods C57BL6 mice were fed either a chow diet (C) or a high-fat diet (HFD) (F) for 11 weeks to induce obesity. Mice were then randomized to receive either a western diet (WD) (CC or FC) or a yogurt-supplemented WD (CY or FY) for 3 weeks to evaluate the impact of yogurt consumption on markers of energy metabolism, metabolic endotoxemia, chronic inflammation, and the gut microbiota. Biological samples were collected at necropsy (Week 14): Plasma samples were used to assess glucose by colorimetric method, insulin and lipopolysaccharide-binding protein (LBP) levels by ELISA kits, and cytokine levels by a Meso Scale Discovery biomarker assay kit. Cecal samples were used to assess the microbiota by 16S rRNA sequencing. Results Female mice showed a mild increase in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR; calculated from plasma glucose and insulin levels) in response to HFD. Among male mice, however, compared to CC and CY, FC had significantly higher HOMA-IR (p < 0.05 for comparisons between CC-FC & CY-FC by ANOVA, followed by Tukey HSD as the post-hoc test), accompanied by significantly elevated plasma LBP, TNF-α, IL-10, and leptin levels (p < 0.05 by ANOVA & Tukey HSD), as well as higher relative abundance of cecal bacteria, Dorea longicatena (p < 0.05 by likelihood-ratio test), which was associated with elevated risks for metabolic syndrome and diabetes. In contrast, FY significantly attenuated HOMA-IR and plasma LBP, IL-10, TNF-α, and leptin levels compared to FC (p < 0.05 by ANOVA & Tukey HSD). Also, beta-diversity of cecal microbiota from FY was significantly different from the rest of three groups (p < 0.01 by Analysis of similarities), and the relative abundance of Dorea longicatena was significantly attenuated in FY than in FC (p < 0.05 by likelihood-ratio test). Conclusions Yogurt supplementation attenuated HFD-induced insulin resistance while modulating the gut microbiota, markers of metabolic endotoxemia, and systemic inflammation. This study helps explain the specific mechanisms by which yogurt consumption modulates inflammation in obesity. Funding Sources National Dairy Council, University of Wisconsin Dairy Innovation Hub.