Caloric restriction chronically impairs metabolic programming in mice.
Although obesity rates are rapidly rising, caloric restriction remains one of the few safe therapies. Here we tested the hypothesis that obesity-associated disorders are caused by increased adipose tissue as opposed to excess dietary lipids. Fat mass (FM) of lean C57B6 mice fed a high-fat diet (HFD; FMC mice) was "clamped" to match the FM of mice maintained on a low-fat diet (standard diet [SD] mice). FMC mice displayed improved glucose and insulin tolerance as compared with ad libitum HFD mice (P < 0.001) or SD mice (P < 0.05). These improvements were associated with fewer signs of inflammation, consistent with the less-impaired metabolism. In follow-up studies, diet-induced obese mice were food restricted for 5 weeks to achieve FM levels identical with those of age-matched SD mice. Previously, obese mice exhibited improved glucose and insulin tolerance but showed markedly increased fasting-induced hyperphagia (P < 0.001). When mice were given ad libitum access to the HFD, the hyperphagia of these mice led to accelerated body weight gain as compared with otherwise matched controls without a history of obesity. These results suggest that although caloric restriction on a HFD provides metabolic benefits, maintaining those benefits may require lifelong continuation, at least in individuals with a history of obesity.
Department of Internal Medicine, Metabolic Diseases Institute, Division of Endocrinology, University of Cincinnati, Cincinnati, OH, USA.
Henriette
H
Kirchner
Susanna M
SM
Hofmann
Antje
A
Fischer-Rosinský
Jazzminn
J
Hembree
William
W
Abplanalp
Nickki
N
Ottaway
Elizabeth
E
Donelan
Radha
R
Krishna
Stephen C
SC
Woods
Timo D
TD
Müller
Joachim
J
Spranger
Diego
D
Perez-Tilve
Paul T
PT
Pfluger
Matthias H
MH
Tschöp
Kirk M
KM
Habegger
D052436:Adipose Tissue, White / Q000378:metabolism*; D050154:Adiposity; D000818:Animals; D031204:Caloric Restriction / Q000009:adverse effects*; D059305:Diet, High-Fat / Q000009:adverse effects; D004038:Diet, Reducing / Q000009:adverse effects; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D018149:Glucose Intolerance / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D006963:Hyperphagia / Q000209:etiology; D007031:Hypothalamus / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000178:diet therapy / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D011897:Random Allocation; D055502:Secondary Prevention; D015430:Weight Gain
D018836:Inflammation Mediators