Roles of leptin in the recovery of muscle and bone by reloading after mechanical unloading in high fat diet-fed obese mice

Naoyuki Kawao,Masayoshi Ishida,Hiroshi Kaji,Jonathan M Peterson

doi:10.1371/journal.pone.0224403

Abstract

Muscle and bone masses are elevated by the increased mechanical stress associated with body weight gain in obesity. However, the mechanisms by which obesity affects muscle and bone remain unclear. We herein investigated the roles of obesity and humoral factors from adipose tissue in the recovery phase after reloading from disuse-induced muscle wasting and bone loss using normal diet (ND)- or high fat diet (HFD)-fed mice with hindlimb unloading (HU) and subsequent reloading. Obesity did not affect decreases in trabecular bone mineral density (BMD), muscle mass in the lower leg, or grip strength in HU mice. Obesity significantly increased trabecular BMD, muscle mass in the lower leg, and grip strength in reloading mice over those in reloading mice fed ND. Among the humoral factors in epididymal and subcutaneous adipose tissue, leptin mRNA levels were significantly higher in reloading mice fed HFD than in mice fed ND. Moreover, circulating leptin levels were significantly higher in reloading mice fed HFD than in mice fed ND. Leptin mRNA levels in epididymal adipose tissue or serum leptin levels positively correlated with the increases in trabecular BMD, total muscle mass, and grip strength in reloading mice fed ND and HFD. The present study is the first to demonstrate that obesity enhances the recovery of bone and muscle masses as well as strength decreased by disuse after reloading in mice. Leptin may contribute to the recovery of muscle and bone enhanced by obesity in mice.

Highlights

Increasing evidence suggests that obesity affects bone metabolism and muscle functions [1,2,3]
Relative changes (% before reloading) in body weight, calorie intake, fat mass, bone mineral density (BMD), muscle mass, and grip strength were calculated by dividing each parameter before reloading by that after reloading for 4 weeks
Roles of leptin in muscle and bone recovery in obesity regression analysis was performed on serum leptin levels and relative changes in trabecular BMD in the tibia, total muscle mass, or grip strength in mice fed normal diet (ND) or high fat diet (HFD) after reloading for 4 weeks

Summary

Introduction

Increasing evidence suggests that obesity affects bone metabolism and muscle functions [1,2,3]. Obese individuals have a higher bone mineral density (BMD) than non-obese individuals [4]. De Laet et al revealed that obesity reduced self-reported overall and hip fracture risks in a meta-analysis [5]. Compston et al reported that obesity is a risk factor for ankle and upper leg fractures in postmenopausal women, suggesting that obesity differently affects bone metabolism by the sites [6]. In obese mice, tibial bone mass is increased by enhancing mechanical stress associated with body weight gain, but subsequently reduced by impairing bone metabolism [7]. Viljakainen et al revealed that indices of bone metabolism

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