Body weight homeostat that regulates fat mass independently of leptin in rats and mice

Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):427-432. doi: 10.1073/pnas.1715687114. Epub 2017 Dec 26.


Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat ("gravitostat") that regulates fat mass.

Keywords: diet-induced obesity; glucose metabolism; osteocytes; weight loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism*
  • Animals
  • Body Weight / physiology*
  • Diet, High-Fat / adverse effects
  • Energy Intake / drug effects
  • Energy Intake / physiology
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology
  • Gene Expression Regulation / drug effects
  • Homeostasis / drug effects*
  • Homeostasis / physiology
  • Leptin / administration & dosage
  • Leptin / pharmacology*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Obese
  • Obesity / etiology
  • Obesity / genetics
  • Obesity / metabolism*
  • Osteocytes / metabolism
  • Rats, Sprague-Dawley
  • Weight Loss / drug effects
  • Weight Loss / physiology


  • Leptin