Persistent diet-induced obesity in male C57BL/6 mice resulting from temporary obesigenic diets.
BACKGROUND
Does diet-induced obesity persist after an obesigenic diet is removed? We investigated this question by providing male C57BL/6 mice with free access to two different obesigenic diets followed by a switch to chow to determine if obesity was reversible.


RESULTS
Male C57BL/6 mice were randomly assigned to five weight-matched groups: 1) C group that continuously received a chow diet; 2) HF group on a 60% high fat diet; 3) EN group on the high fat diet plus liquid Ensure; 4) HF-C group switched from high fat to chow after 7 weeks; 5) EN-C group switched from high fat plus Ensure to chow after 7 weeks. All food intake was ad libitum. Body weight was increased after 7 weeks on both obesigenic diets (44.6+/-0.65, 39.8+/-0.63, and 28.6+/-0.63 g for EN, HF, and C groups, respectively) and resulted in elevated concentrations of serum insulin, glucose, and leptin and lower serum triglycerides. Development of obesity in HF and EN mice was caused by increased energy intake and a relative decrease of average energy output along with decreased ambulatory activity. After the switch to chow, the HF-C and EN-C groups lost weight but subsequently maintained a state of persistent obesity in comparison to the C group (34.8+/-1.2, 34.1+/-1.2 vs. 30.8+/-0.8 g respectively; P<0.05) with a 40-50% increase of body fat. All serum hormones and metabolites returned to control levels with the exception of a trend for increased leptin. The HF-C and EN-C groups had an average energy output in line with the C group and the persistent obesity was maintained despite a non-significant increase of energy intake of less than 1 kcal/d at the end of the study.


CONCLUSIONS
Our results illustrate the importance of considering the history of energy imbalance in determining body weight and that a persistent elevation of body weight after removal of obesigenic diets can result from very small increases of energy intake.
Guo
Juen
J
Laboratory of Biological Modeling, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Jou
William
W
Gavrilova
Oksana
O
Hall
Kevin D
KD
D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D050218:Body Fat Distribution; D001835:Body Weight; D004032:Diet / Q000009:adverse effects*; D004195:Disease Models, Animal; D002149:Energy Intake; D004734:Energy Metabolism; D005990:Glycerol / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D009765:Obesity / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
D001786:Blood Glucose; D020738:Leptin; D005990:Glycerol