title: Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet.
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.
authors.affiliation: Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Megumi
authors.initials: M
authors.lastname: Hatori
authors.forename: Christopher
authors.initials: C
authors.lastname: Vollmers
authors.forename: Amir
authors.initials: A
authors.lastname: Zarrinpar
authors.forename: Luciano
authors.initials: L
authors.lastname: DiTacchio
authors.forename: Eric A
authors.initials: EA
authors.lastname: Bushong
authors.forename: Shubhroz
authors.initials: S
authors.lastname: Gill
authors.forename: Mathias
authors.initials: M
authors.lastname: Leblanc
authors.forename: Amandine
authors.initials: A
authors.lastname: Chaix
authors.forename: Matthew
authors.initials: M
authors.lastname: Joens
authors.forename: James A J
authors.initials: JA
authors.lastname: Fitzpatrick
authors.forename: Mark H
authors.initials: MH
authors.lastname: Ellisman
authors.forename: Satchidananda
authors.initials: S
authors.lastname: Panda
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism / Q000473:pathology; D052436:Adipose Tissue, White / Q000378:metabolism; D050154:Adiposity; D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis; D002784:Cholesterol / Q000097:blood; D002940:Circadian Rhythm; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004435:Eating; D002149:Energy Intake; D004734:Energy Metabolism; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008659:Metabolic Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D010101:Oxygen Consumption; D010766:Phosphorylation; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D015430:Weight Gain
chemical_list: D001647:Bile Acids and Salts; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D016207:Cytokines; D002784:Cholesterol; C546843:mTOR protein, mouse; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase; D005947:Glucose