Weighing the evidence for a body mass-regulating gravitostat

January 23, 2018
115 (7) E1334
Letter
Reply to Lund: Where does the gravitostat fit in?
Claes Ohlsson, John-Olov Jansson
The intriguing paper by Jansson et al. (1) reports the identification of a body mass-regulating homeostat that operates in rodents independently of leptin. In response to implantation of capsules weighing 15% of body weight the authors observed that ∼80% of this load was offset by a reduction in biological body weight. This interesting effect was attributed to a reduction in fat mass and explained by decreased food intake. Based upon studies of osteocyte-depleted mice, the authors propose that the lower extremities harbor an osteocyte-dependent gravitostat that regulates body weight. According to this model, elevations in body weight are sensed by osteocytes as an increased strain and, in response, an unknown anorexigenic factor is secreted from the weight-bearing bones.
If this proposed gravitostat responds to alterations in body load then exposure to hypergravity would be expected to cause hypophagia and weight loss, whereas a microgravitational environment should promote hyperphagia and weight gain. Along these lines, it is very interesting to note that rodents have previously been reported to respond to hypergravity (2G) by an acute decrease in food intake and a lowering of total body and fat mass (2). Furthermore, when exposed to microgravity, the lipid content of adipose tissue has been observed to increase (2). Thus, gravitational alterations seem to produce effects that agree with the gravitostat model of body weight regulation, at least in rodents. But what about humans? Data from space missions show that astronauts experience a decrease in body mass while in the microgravitational environment (35) and that this is due to a 23–43% decrease in caloric intake (4). It must be emphasized that space travel is not a controlled experiment and that astronauts also experience an altered light–dark cycle and an increased exposure to ionizing radiation, both of which are factors that have been proposed to initiate a physiological stress response that decreases appetite, perhaps to an extent that it overrules reduced secretion of an anorexigenic factor from osteocytes. Thus, studies using bed rest, a ground-based model of microgravity (4), might provide more definitive answers, but such studies also reported a decrease in body weight (6, 7) and indicated that increased time spent in bed might decrease appetite (7). These findings contradict the existence of a gravitostat in humans.
As a final note, it is important to highlight that the proposal made by Jansson et al. (1) is in line with what has previously been stated by Ravussin et al. (8), namely that “a stress signal derived from an organ distinct from adipose tissue could drive expression of a catabolic factor.” Given that microgravity does not seem to increase appetite in humans, it could be speculated that leptin and the proposed gravitostat are two complementary systems, with leptin being a signal that acts preferentially to defend against starvation (8, 9), whereas the unknown catabolic signal produced by the gravitostat might act primarily as a defense against adiposity. Whether or not this is true should be tested by human intervention studies.

References

1
J-O Jansson, et al., Body weight homeostat that regulates fat mass independently of leptin in rats and mice. Proc Natl Acad Sci USA 115, 427–432 (2018).
2
LE Warren, BA Horwitz, CA Fuller, Gravity and body mass regulation. J Gravit Physiol 4, 89–92 (1997).
3
HW Lane, RJ Gretebeck, SM Smith, Nutrition, endocrinology, and body composition during space flight. Nutr Res 18, 1923–1934 (1998).
4
M Heer, M Elia, P Ritz, Energy and fluid metabolism in microgravity. Curr Opin Clin Nutr Metab Care 4, 307–311 (2001).
5
MS Da Silva, et al., Anorexia in space and possible etiologies: An overview. Nutrition 18, 805–813 (2002).
6
S Blanc, et al., Energy and water metabolism, body composition, and hormonal changes induced by 42 days of enforced inactivity and simulated weightlessness. J Clin Endocrinol Metab 83, 4289–4297 (1998).
7
T Debevec, EJ Simpson, IB Mekjavic, O Eiken, IA Macdonald, Effects of prolonged hypoxia and bed rest on appetite and appetite-related hormones. Appetite 107, 28–37 (2016).
8
Y Ravussin, RL Leibel, Jr AW Ferrante, A missing link in body weight homeostasis: The catabolic signal of the overfed state. Cell Metab 20, 565–572 (2014).
9
JS Flier, E Maratos-Flier, Leptin’s physiological role: Does the emperor of energy balance have no clothes? Cell Metab 26, 24–26 (2017).

Information & Authors

Information

Published in

Go to Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Vol. 115 | No. 7
February 13, 2018
PubMed: 29363607

Classifications

Submission history

Published online: January 23, 2018
Published in issue: February 13, 2018

Authors

Affiliations

Unit for Integrated Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, 2200 Copenhagen N, Denmark

Notes

Author contributions: J.L. analyzed data and wrote the paper.

Competing Interests

The author declares no conflict of interest.

Metrics & Citations

Metrics

Note: The article usage is presented with a three- to four-day delay and will update daily once available. Due to ths delay, usage data will not appear immediately following publication. Citation information is sourced from Crossref Cited-by service.


Citation statements




Altmetrics

Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.

Cited by

    Loading...

    View Options

    View options

    PDF format

    Download this article as a PDF file

    DOWNLOAD PDF

    Get Access

    Login options

    Check if you have access through your login credentials or your institution to get full access on this article.

    Personal login Institutional Login

    Recommend to a librarian

    Recommend PNAS to a Librarian

    Purchase options

    Purchase this article to access the full text.

    Single Article Purchase

    Weighing the evidence for a body mass-regulating gravitostat
    Proceedings of the National Academy of Sciences
    • Vol. 115
    • No. 7
    • pp. 1395-E1700

    Media

    Figures

    Tables

    Other

    Share

    Share

    Share article link

    Share on social media