The dual hypothesis of homeostatic body weight regulation, including gravity-dependent and leptin-dependent actions

Philos Trans R Soc Lond B Biol Sci. 2023 Oct 23;378(1888):20220219. doi: 10.1098/rstb.2022.0219. Epub 2023 Sep 4.

Abstract

Body weight is tightly regulated when outside the normal range. It has been proposed that there are individual-specific lower and upper intervention points for when the homeostatic regulation of body weight is initiated. The nature of the homeostatic mechanisms regulating body weight at the lower and upper ends of the body weight spectrum might differ. Previous studies demonstrate that leptin is the main regulator of body weight at the lower end of the body weight spectrum. We have proposed that land-living animals use gravity to regulate their body weight. We named this homeostatic system the gravitostat and proposed that there are two components of the gravitostat. First, an obvious mechanism involves increased energy consumption in relation to body weight when working against gravity on land. In addition, we propose that there exists a component, involving sensing of the body weight by osteocytes in the weight-bearing bones, resulting in a feedback regulation of energy metabolism and body weight. The gravity-dependent homeostatic regulation is mainly active in obese mice. We, herein, propose the dual hypothesis of body weight regulation, including gravity-dependent actions (= gravitostat) at the upper end and leptin-dependent actions at the lower end of the body weight spectrum. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.

Keywords: body weight homeostasis; body weight sensing; gravitostat; leptin; loading; obesity.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Energy Metabolism
  • Homeostasis
  • Leptin*
  • Mice
  • Obesity*

Substances

  • Leptin