Age of Cafeteria Diet Onset Influences Obesity Phenotype in Mice in a Sex-Specific Manner

We investigated the influence of sex and the age of obesogenic diet initiation on the obesity phenotypes at a later age. C57Bl mice started the Cafeteria Diet (CafD, with increased fat and carbohydrates, ad libitum, from 7 weeks of age (7CafD, pre-puberty) or 17 weeks of age (7CafD, post-puberty) while control C57Bl mice were fed regular chow. At 27 weeks of age, 7CafD males (n = 9) compared to 17CafD males (n = 7) had lower body weight, white adipose tissue (WAT) relative weight, and plasma cholesterol levels, and a higher expression of thermogenic genes in WAT and brown adipose tissue (BAT), and fatty acid oxidation (FAO) and insulin signalling genes in muscles. The 7CafD females (n = 8), compared to 17CafD females (n = 6), had higher plasma triglyceride levels and hepatic glycogen content, but lower insulin sensitivity and hepatic expression of FAO and insulin signalling genes. The 7CafD females, compared to 7CafD males, had more WAT, and a reduced expression of FAO genes in muscles and thermogenic genes in WAT. The 17CafD females, compared to 17CafD males, had lower plasma leptin and insulin levels, and higher insulin sensitivity and expression of insulin signalling genes in the liver and muscles. Thus, the initiation of the obesogenic diet before puberty led to a more adaptive metabolic phenotypes in males, and after puberty, in females.