Milk protects against sarcopenic obesity due to increase in the genus Akkermansia in faeces of db/db mice

Abstract

Background: Sarcopenic obesity, a combination of sarcopenia and obesity, is a pathological feature of type 2 diabetes. Several human studies have shown that milk is useful in the prevention of sarcopenia. This study was aimed at clarifying the effect of milk on the prevention of sarcopenic obesity in db/db mice. Methods: A randomized and investigator-blinded study was conducted using male db/db mice. Eight-week-old db/db mice were housed for 8 weeks and fed milk (100 μL/day) using a sonde. The faecal microbiota transplantation (FMT) group received antibiotics for 2 weeks, starting at 6 weeks of age, followed by FMT twice a week until 16 weeks of age. Results: Milk administration to db/db mice increased grip strength (Milk−: 164.2 ± 4.7 g, Milk+: 230.2 ± 56.0 g, P = 0.017), muscle mass (soleus muscle, Milk−: 164.2 ± 4.7 mg, Milk+: 230.2 ± 56.0 mg, P < 0.001; plantaris muscle, Milk−: 13.3 ± 1.2 mg, Milk+: 16.0 ± 1.7 mg, P < 0.001) and decreased visceral fat mass (Milk−: 2.39 ± 0.08 g, Milk+: 1.98 ± 0.04 mg, P < 0.001), resulting in a significant increase in physical activity (light: P = 0.013, dark: P = 0.034). FMT from mice fed milk not only improved sarcopenic obesity but also significantly improved glucose intolerance. Microarray analysis of gene expression in the small intestine revealed that the expression of amino acid absorption transporter genes, namely, SIc7a5 (P = 0.010), SIc7a1 (P = 0.015), Ppp1r15a (P = 0.041) and SIc7a11 (P = 0.029), was elevated in mice fed milk. In 16S rRNA sequencing of gut microbiota, the genus Akkermansia was increased in both the mice fed milk and the FMT group from the mice fed milk. Conclusions: The findings of this study suggest that besides increasing the intake of nutrients, such as amino acids, milk consumption also changes the intestinal environment, which might contribute to the mechanism of milk-induced improvement of sarcopenic obesity.