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

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.

Figure 1.

Schematic illustration of leptin's effects in body weight homeostasis. Leptin, produced by white adipose tissue in proportion to fat mass, acts within the brain, especially the hypothalamus, to decrease feeding and increase energy expenditure, as part of a homeostatic feed-back loop to suppress fat mass.

Figure 2.

Increased loading decreases body weight in rodents and pigeons. (a) Total weight (loading + biological body weight) of mice with intraperitoneal load is normalized after two weeks. Adapted from [17]. (b) Biological body weight of mice is decreased to compensate for subcutaneous experimental load. Adapted from [17]. (c) Decrease in biological body weight caused by intraperitoneal load is reversible in mice. Adapted from [17]. (d) Biological body weight of pigeons is reversibly decreased to compensate for load glued to the back. Adapted from [30].

Figure 3.

Hypothesis for how leptin and the gravitostat act in concert to regulate body weight homeostasis. (a) The leptin and gravitostat systems in the regulation of body weight (adapted from [17]). (b) The dose–response curve for the effect of leptin (blue line) is shifted to the left, reflecting that treatment with this hormone decreases body weight mainly in lean animals. By contrast, the dose–response curve for the effect of the gravitostat (black line) is shifted to the right, reflecting that the effect of the gravitostat decreases body weight more efficiently in obese mice. Adapted from [29].

Figure 4.

The dual hypothesis of body weight regulation, including gravity-dependent and leptin-dependent actions. For explanation of this figure, please see the main text. Adapted from [16].