Replacing Part of Glucose with Galactose in the Postweaning Diet Protects Female But Not Male Mice from High-Fat Diet–Induced Adiposity in Later Life

Abstract

ABSTRACT Background Duration of breastfeeding is positively associated with decreased adiposity and increased metabolic health in later life, which might be related to galactose. Objective The aim of this study was to investigate if partial replacement of glucose with galactose in the postweaning diet had a metabolic programming effect. Methods Male and female mice (C57BL/6JRccHsd) received an isocaloric diet (16 energy% fat; 64 energy% carbohydrates; 20 energy% protein) with either glucose (32 energy%) (GLU) or glucose + galactose (GLU + GAL, 16 energy% each) for 3 wk postweaning. Afterwards, all mice were switched to the same 40 energy% high-fat diet (HFD) for 9 wk to evaluate potential programming effects in an obesogenic environment. Data were analyzed within sex. Results Female body weight (−14%) and fat mass (−47%) were significantly lower at the end of the HFD period (both P < 0.001) among those fed GLU + GAL than among those fed GLU; effects in males were in line with these findings but nonsignificant. Food intake was affected in GLU + GAL–fed females (+8% on postweaning diet, −9% on HFD) compared with GLU-fed females, but not for hypothalamic transcript levels at endpoint. Also, in GLU + GAL–fed females, serum insulin concentrations (−48%, P  < 0.05) and the associated homeostasis model assessment of insulin resistance (HOMA-IR) were significantly lower ( P < 0.05) at endpoint, but there were no changes in pancreas morphology. In GLU + GAL–fed females, expression of insulin receptor substrate 2 (Irs2) (−27%, P  < 0.01 ; −44%, P  < 0.001) and the adipocyte size markers leptin (Lep) (−40%, P  < 0.05; −63% , P  < 0.05) and mesoderm-specific transcript homolog protein (Mest) (−80%, P < 0.05; −72%, P  < 0.05) was lower in gonadal and subcutaneous white adipose tissue (WAT), respectively. Expression of insulin receptor substrate1 (Irs1) (−24%, P  < 0.05) was only lower in subcutaneous WAT in GLU + GAL–fed females. Conclusions Partial replacement of glucose with galactose, resulting in a 1:1 ratio mimicking lactose, in a 3-wk postweaning diet lowered body weight, adiposity, HOMA-IR, and expression of WAT insulin signaling in HFD-challenged female mice in later life. This suggests that prolonged galactose intake may improve metabolic and overall health in later life.