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PMID: 21411766 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Effects of chronic weight perturbation on energy homeostasis and brain structure in mice.

American journal of physiology. Regulatory, integrative and comparative physiology ·Vol. 300 ·No. 6 ·2011-06-00 ·Pages R1352-62

Ravussin Y, Gutman R, Diano S, Shanabrough M, Borok E, Sarman B, Lehmann A, LeDuc CA, Rosenbaum M, Horvath TL, Leibel RL

Abstract

Maintenance of reduced body weight in lean and obese human subjects results in the persistent decrease in energy expenditure below what can be accounted for by changes in body mass and composition. Genetic and developmental factors may determine a central nervous system (CNS)-mediated minimum threshold of somatic energy stores below which behavioral and metabolic compensations for weight loss are invoked. A critical question is whether this threshold can be altered by environmental influences and by what mechanisms such alterations might be achieved. We examined the bioenergetic, behavioral, and CNS structural responses to weight reduction of diet-induced obese (DIO) and never-obese (CON) C57BL/6J male mice. We found that weight-reduced (WR) DIO-WR and CON-WR animals showed reductions in energy expenditure, adjusted for body mass and composition, comparable (-10-15%) to those seen in human subjects. The proportion of excitatory synapses on arcuate nucleus proopiomelanocortin neurons was decreased by ∼50% in both DIO-WR and CON-WR mice. These data suggest that prolonged maintenance of an elevated body weight (fat) alters energy homeostatic systems to defend a higher level of body fat. The synaptic changes could provide a neural substrate for the disproportionate decline in energy expenditure in weight-reduced individuals. This response to chronic weight elevation may also occur in humans. The mouse model described here could help to identify the molecular/cellular mechanisms underlying both the defense mechanisms against sustained weight loss and the upward resetting of those mechanisms following sustained weight gain.

MeSH Terms
Animals Arcuate Nucleus of Hypothalamus/anatomy & histology,cytology,physiology Body Composition/physiology Body Weight/drug effects,physiology Brain/anatomy & histology,physiology Caloric Restriction Dietary Fats/pharmacology Energy Metabolism/physiology Homeostasis/physiology Male Mice Mice, Inbred C57BL Models, Animal Neurons/cytology,physiology Synapses/physiology Weight Gain/physiology Weight Loss/physiology
Chemicals
Dietary Fats
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Ravussin Y
1Department of Pediatrics, Division of Molecular Genetics, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
Gutman R
Diano S
Shanabrough M
Borok E
Sarman B
Lehmann A
LeDuc C A
Rosenbaum M
Horvath T L
Leibel R L
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Article Info
Journal
American journal of physiology. Regulatory, integrative and comparative physiology
Abbr.
Am J Physiol Regul Integr Comp Physiol
ISSN
1522-1490
DOI
10.1152/ajpregu.00429.2010
Published
2011-06-00
Epub
2011-00-16
Pages
R1352-62
Language
English
Region
United States
NLM ID
100901230
PMCID
PMC3119157
Subset
IM
Grants
NIDDK NIH HHS · P30-DK-63068 · United States
PHS HHS · 066518 · United States
NIDDK NIH HHS · R01 DK064773 · United States
NIDDK NIH HHS · P30-DK-26687 · United States
NIDDK NIH HHS · R01 DK052431 · United States
NIDDK NIH HHS · R01-DK- · United States
NIDDK NIH HHS · R01-DK- 080000 · United States
External Links
PubMed source DOI: 10.1152/ajpregu.00429.2010 PMC Full Text View journal details
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