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

John Olov Jansson, Vilborg Palsdottir, Daniel A. Hägg, Erik Schéle, Suzanne L. Dickson, Fredrik Anesten, Tina Bake, Mikael Montelius, Jakob Bellman, Maria E. Johansson, Roger D. Cone, Daniel J. Drucker, Jianyao Wu, Biljana Aleksic, Anna E. Törnqvist, Klara Sjögren, Jan Åke Gustafsson, Sara H. Windahl, Claes Ohlsson

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)427-432
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number2
DOIs
StatePublished - Jan 9 2017

Keywords

  • Diet-induced obesity
  • Glucose metabolism
  • Osteocytes
  • Weight loss

ASJC Scopus subject areas

  • General

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