Short-term food restriction followed by controlled refeeding promotes gorging behavior, enhances fat deposition, and diminishes insulin sensitivity in mice.
Rodents are commonly used in food restriction refeeding studies to investigate weight regain. Mice that are rationed food every 24 h may consume all allocated food in a short time (gorge) and therefore undergo a brief well-fed period followed by an extended fasted period until the next day's food allotment. These exaggerated metabolic states are not typical in mice fed ad libitum (nibbling). The aim of the current study was to elucidate the intraday and cumulative metabolic consequences of gorging (induced by food restriction) in mice during controlled refeeding. Accordingly, following a temporary food restriction, mice were fed rations similar to intakes of controls fed ad libitum. Temporary food restriction initiated gorging behavior that persisted during refeeding; consequently, metabolism-related measurements were obtained in the gorging mice during their daily fed and fasted metabolic states. Robust differences in adipose tissue lipogenic and inflammatory gene expression were found in the gorging mice by metabolic state (fed versus fasted). Additionally, despite a reduced cumulative food intake compared to mice fed ad libitum, restriction-induced gorging mice had increased intraabdominal fat accumulation, diminished hepatic and peripheral insulin sensitivity, and a gene expression profile favoring lipid deposition. Our findings highlight the intraday differences in gene expression in gorging mice before and after feeding that confound comparisons with mice fed ad libitum, or nibbling. The present study also provides evidence that weight regain following food restriction is associated with cumulative metabolic and behavioral abnormalities in mice.
Department of Human Sciences, College of Education and Human Ecology, The Ohio State University, Columbus, OH 43210, USA.
Kara L
KL
Kliewer
Department of Human Sciences, College of Education and Human Ecology, The Ohio State University, Columbus, OH 43210, USA.
Jia-Yu
JY
Ke
Laboratory of Mitochondria and Metabolic Diseases/ Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute/ Molecular Medicine, Gachon University Graduate School of Medicine, Incheon 406-840, Korea.
Hui-Young
HY
Lee
Department of Human Sciences, College of Education and Human Ecology, The Ohio State University, Columbus, OH 43210, USA.
Michael B
MB
Stout
Department of Human Sciences, College of Education and Human Ecology, The Ohio State University, Columbus, OH 43210, USA.
Rachel M
RM
Cole
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06519, USA.
Varman T
VT
Samuel
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06519, USA; Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06519, USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06519, USA.
Gerald I
GI
Shulman
Department of Human Sciences, College of Education and Human Ecology, The Ohio State University, Columbus, OH 43210, USA. Electronic address: Belury.1@osu.edu.
Martha A
MA
Belury
D054392:Adipokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D050154:Adiposity; D000818:Animals; D001522:Behavior, Animal; D031204:Caloric Restriction / Q000009:adverse effects*; D003433:Crosses, Genetic; D005247:Feeding Behavior; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006963:Hyperphagia / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D011897:Random Allocation; D015430:Weight Gain
D054392:Adipokines; D018836:Inflammation Mediators
Adiposity; Food restriction; Gorging; Insulin sensitivity; Refeeding; Weight regain