Endocrine Abstracts

Despite its popularity, the physiological impact of the 5:2 diet (2 non-consecutive fast days and 5 normal feeding days) in mice remains unclear. We have previously reported that while this fasting strategy accelerates skeletal growth in both sexes, it only reduces weight in males. To advance our understanding of its broader metabolic impact, adolescent (7-week old) male and female C57BL/6J mice received standard rodent chow in an ad-libitum or 5:2 pattern for 24 days. While 5:2 diet-fed mice induced rebound overeating on feeding days, neither sex showed significant cumulative hyperphagia. Tibial epiphyseal plate width (EPW), an index of skeletal growth rate, and marrow adipocyte size were elevated by 9% and 31% in males (P=0.027; 0.038). Proportionate inguinal white adipose tissue (WAT) mass increased in 5:2-fed males and females by 37% and 22% respectively (P=0.006, 0.034), with a 17-20% elevation in adipocyte size (P<0.05). Neither gonadal nor retroperitoneal WAT were significantly affected. Proportionate interscapular brown AT (BAT) was elevated by 37% in both sexes (P=0.0001). Gas chromatography with flame ionisation detection revealed parallel increases (11-35%) in the relative amounts of saturated (C14:0; C16:0; C18:0; C20:0) fatty acids (FAs) in BAT in males and females (P<0.05) and reductions (12-35%) in mono- and poly-unsaturated FAs (C16:1n9; C20:1n9; C20:4n6) including essential FAs (C18:1n7; C18:2n6 and C18:3n3) (P<0.05). In contrast, while hepatic essential FA content (C18:2n6; C18:3n3) was reduced and C20 omega-6 (C20:3n6) FA content was increased (17%) in both sexes (P<0.01), saturated FA (C18:0) content was only increased (25%) in males (P=0.037). Thus, the 5:2 diet induces a surprising combination of sex-independent and sex-specific effects. The increase in subcutaneous WAT and interscapular BAT mass suggests improved heat retention in both sexes, accompanied by a broader preferential storage of saturated FAs. However, as a weight loss strategy, the 5:2 diet is only effective in males.