Glycine supplementation during calorie restriction accelerates fat loss and protects against further muscle loss in obese mice

Abstract

Calorie restriction (CR) reduces co-morbidities associated with obesity, but also reduces lean mass thereby predisposing people to weight regain. Since we demonstrated that glycine supplementation can reduce inflammation and muscle wasting, we hypothesized that glycine supplementation during CR would preserve muscle mass in mice. High-fat fed male C57BL/6 mice underwent 20 days CR (40% reduced calories) supplemented with glycine (1g/kg/day; n=15, GLY) or l-alanine (n=15, ALA). Body composition and glucose tolerance were assessed and hindlimb skeletal muscles and epididymal fat were collected. Eight weeks of a high-fat diet (HFD) induced obesity and glucose intolerance. CR caused rapid weight loss (ALA: 20%, GLY: 21%, P<0.01), reduced whole-body fat mass (ALA: 41%, GLY: 49% P<0.01), and restored glucose tolerance to control values in ALA and GLY groups. GLY treated mice lost more whole-body fat mass (14%, p<0.05) and epididymal fat mass (26%, P<0.05), less lean mass (27%, P<0.05), and had better preserved quadriceps muscle mass (4%, P<0.01) than ALA treated mice after 20d CR. Compared to the HFD group, pro-inflammatory genes were lower (P<0.05), metabolic genes higher (P<0.05) and S6 protein phosphorylation lower after CR, but not different between ALA and GLY groups. There were significant correlations between %initial fat mass (pre CR) and the mRNA expression of genes involved in inflammation (r=0.51 to 0.68, P<0.05), protein breakdown (r=-0.66 to-0.37, P<0.05) and metabolism (r=-0.59 to-0.47, P<0.05) after CR. Taken together, these findings suggest that glycine supplementation during CR may be beneficial for preserving muscle mass and stimulating loss of adipose tissue.