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

Journal article
Authors John-Olov Jansson
Vilborg Palsdottir
Daniel Hägg
Erik Schéle
Suzanne L. Dickson
Fredrik Anesten
Tina Bake
Mikael Montelius
Jakob Bellman
Maria E I Johansson
Roger D Cone
Daniel J Drucker
Jianyao Wu
Biljana Aleksic
Anna E Törnqvist
Klara Sjögren
Jan-Åke Gustafsson
Sara H Windahl
Claes Ohlsson
Published in Proceedings of the National Academy of Sciences of the United States of America
Volume 115
Issue 2
Pages 427-432
ISSN 1091-6490
Publication year 2018
Published at Institute of Clinical Sciences, Department of Radiation Physics
Institute of Neuroscience and Physiology, Department of Physiology
Centre for Bone and Arthritis Research
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Pages 427-432
Language en
Links dx.doi.org/10.1073/pnas.1715687114
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Clinical physiology

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.

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