Yogurt Consumption Improves Insulin Sensitivity and Hepatic Insulin Action in a Diet Induced Mouse Model of Obesity and Type 2 Diabetes

Abstract

Abstract Objectives We investigated the effect of yogurt consumption at 8% energy intake on insulin sensitivity in mice fed high-fat high-sucrose diet that contains a protein mixture representative of US diet (HFHS-PM). Methods Yogurt (2% fat, 5% protein, 7% carbohydrate, Lactobacillus bulgaricus CNCM I-1519, Streptococcus thermophilus CNCM I-1630) was lyophilized and incorporated into the HFHS-PM diet (HFHS-PM + LYP; 4.8 kcal/g). The control group was kept on the HFHS-PM diet (4.8 kcal/g). A group of mice was fed a low-fat low sucrose diet (LFLS-PM; 3.7 kcal/g). Whole-body glucose homeostasis and tissue insulin action were assessed using tracer-coupled hyperinsulinemic-euglycemic clamp studies performed after 12 weeks of dietary intervention. Results At Week 12, mice fed HFHS-PM (n = 36) had increased body weight gain (+10.9 g P < 0.001), fasting glucose (+4.1 mmol/l, P < 0.001) and fasting insulin (+2.7 ng/mL, P < 0.001) when compared to LFLS-PM mice (n = 35). HFHS-PM + LYP fed mice (n = 36) had lower fasting glucose (–0.9 mmol/, P < 0.05) and fasting insulin (–1.1 ng/mL, P < 0.05) as compared to HFHS-PM controls without any impact on body weight gain. Clamp studies revealed that mice fed HFHS-PM (n = 27) had reduced insulin-mediated glucose infusion rate (–17.1 mg/min/kg, P < 0.001) indicating whole-body insulin resistance when compared to LFLS-PM (n = 23). Insulin resistance in HFHS-PM fed animals was linked to increased endogenous glucose production (+7.2 mg/min/kg, P < 0.001) and decrease in the rate of peripheral glucose uptake (–10.3 mg/min/kg, P < 0.001) during the clamp compared to LFLS-PM fed mice. Importantly, mice fed HFHS-PM + LYP (n = 25) exhibited a significantly elevated glucose infusion rate (+3.6 mg/min/kg, P = 0.02), i.e., improved whole-body insulin sensitivity, and a numerical decrease of the endogenous glucose production (–1.9 mg/min/kg, P = 0.06) with lack of changes in peripheral glucose uptake when compared to HFHS-PM mice. Conclusions Incorporation of lyophilized yogurt into the HFHS-PM diet improves insulin sensitivity in a diet-induced mouse model of obesity and type 2 diabetes. The selective improvement of insulin-suppressed endogenous glucose production strongly suggest that the liver is the main target of yogurt beneficial effect. Funding Sources Danone Nutricia Research, Palaiseau, France.