Metabolic dysfunction following weight cycling in male mice.

Abstract

Combatting overweight or obesity can lead to large fluctuations in an individual's body weight, often referred to as weight cycling or 'yo-yo' dieting. Current evidence regarding the potentially damaging effects of these changes is conflicting. Here, we assess the metabolic effects of weight cycling in a murine model, comprising three dietary switches to normal or high-fat diets at 6 week intervals; male C57BL/6 mice were fed either a control (C) or high-fat (F) diet for 6 weeks (n=140/group). C and F groups were then either maintained on their initial diet (CC and FF, respectively) or switched to a high-fat (CF) or control (FC) diet (n=35/group). For the final 6 week interval, CC and CF groups were returned to the control diet (CCC and CFC groups), while FC and FF groups were placed on a high-fat diet (FCF and FFF) (n=28/group). For the majority of metabolic outcomes changes aligned with dietary switches; however, assessment of neuropeptides and receptors involved in appetite regulation and reward signalling pathways reveal variable patterns of expression. Furthermore, we demonstrate that multiple cycling events leads to a significant increase in internal fat deposition, even when compared with animals maintained on a high-fat diet (internal fat: FCF: 7.4±0.2 g vs FFF: 5.6±0.2 g; P<0.01). Increased internal adipose tissue is strongly linked to the development of metabolic syndrome associated conditions such as type 2 diabetes, cardiovascular disease and hypertension. Although further work will be required to elucidate the mechanisms underlying the neuronal control of energy homoeostasis, these studies provide a causative link between weight cycling and adverse health.