Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet.

Authors: Hatori M; Vollmers C; Zarrinpar A; DiTacchio L; Bushong EA; Gill S; Leblanc M; Chaix A; Joens M; Fitzpatrick JA; Ellisman MH; Panda S

Abstract: While diet-induced obesity has been exclusively attributed to increased caloric intake from fat, animals fed a high-fat diet (HFD) ad libitum (ad lib) eat frequently throughout day and night, disrupting the normal feeding cycle. To test whether obesity and metabolic diseases result from HFD or disruption of metabolic cycles, we subjected mice to either ad lib or time-restricted feeding (tRF) of a HFD for 8 hr per day. Mice under tRF consume equivalent calories from HFD as those with ad lib access yet are protected against obesity, hyperinsulinemia, hepatic steatosis, and inflammation and have improved motor coordination. The tRF regimen improved CREB, mTOR, and AMPK pathway function and oscillations of the circadian clock and their target genes' expression. These changes in catabolic and anabolic pathways altered liver metabolome and improved nutrient utilization and energy expenditure. We demonstrate in mice that tRF regimen is a nonpharmacological strategy against obesity and associated diseases.

Keywords: Adenylate Kinase/metabolism; Adipose Tissue, Brown/metabolism/pathology; Adipose Tissue, White/metabolism; Adiposity; Animals; Bile Acids and Salts/biosynthesis; Cholesterol/blood; Circadian Rhythm; Cyclic AMP Response Element-Binding Protein/metabolism; Cytokines/genetics/metabolism; Diet, High-Fat/*adverse effects; *Eating; *Energy Intake; Energy Metabolism; Fatty Liver/etiology/metabolism/prevention & control; Gene Expression; Glucose/metabolism; Homeostasis; Lipid Metabolism; Liver/metabolism/pathology; Male; Metabolic Diseases/etiology/metabolism/*prevention & control; Mice; Mice, Inbred C57BL; Oxygen Consumption; Phosphorylation; Ribosomal Protein S6 Kinases/metabolism; TOR Serine-Threonine Kinases/metabolism; Time Factors; Weight Gain
Journal: Cell metabolism
Volume: 15
Issue: 6
Pages: 848-60
Date: May 23, 2012
PMID: 22608008
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Categories: Aging
Citation:

Hatori M, Vollmers C, Zarrinpar A, DiTacchio L, Bushong EA, Gill S, Leblanc M, Chaix A, Joens M, Fitzpatrick JA, Ellisman MH, Panda S (2012) Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell metabolism 15: 848-60.



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