title: Intermittent fasting induces hypothalamic modifications resulting in low feeding efficiency, low body mass and overeating.
abstract: Intermittent fasting (IF) is an often-used intervention to decrease body mass. In male Sprague-Dawley rats, 24 hour cycles of IF result in light caloric restriction, reduced body mass gain, and significant decreases in the efficiency of energy conversion. Here, we study the metabolic effects of IF in order to uncover mechanisms involved in this lower energy conversion efficiency. After 3 weeks, IF animals displayed overeating during fed periods and lower body mass, accompanied by alterations in energy-related tissue mass. The lower efficiency of energy use was not due to uncoupling of muscle mitochondria. Enhanced lipid oxidation was observed during fasting days, whereas fed days were accompanied by higher metabolic rates. Furthermore, an increased expression of orexigenic neurotransmitters AGRP and NPY in the hypothalamus of IF animals was found, even on feeding days, which could explain the overeating pattern. Together, these effects provide a mechanistic explanation for the lower efficiency of energy conversion observed. Overall, we find that IF promotes changes in hypothalamic function that explain differences in body mass and caloric intake.
authors.affiliation: Departamento de Bioquímica (B.C., C.C.C., A.J.K.), Instituto de Química, Universidade de São Paulo, 05508-000 Brazil; Faculdade de Ciências Médicas (C.S., L.A.V.), Universidade Estadual de Campinas, 13083-970 Brazil; Faculdade de Ciências Aplicadas (I.G.M., F.B.M-G., C.A.G.), Universidade Estadual de Campinas, 13084-350 Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Chausse
authors.forename: Carina
authors.initials: C
authors.lastname: Solon
authors.forename: Camille C
authors.initials: CC
authors.lastname: Caldeira da Silva
authors.forename: Ivan G
authors.initials: IG
authors.lastname: Masselli Dos Reis
authors.forename: Fúlvia B
authors.initials: FB
authors.lastname: Manchado-Gobatto
authors.forename: Claudio A
authors.initials: CA
authors.lastname: Gobatto
authors.forename: Licio A
authors.initials: LA
authors.lastname: Velloso
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Kowaltowski
mesh_terms: D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000502:physiology*; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000502:physiology; D005215:Fasting / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology*; D015870:Gene Expression; D006963:Hyperphagia / Q000503:physiopathology*; D007031:Hypothalamus / Q000378:metabolism*; D015151:Immunoblotting; D020738:Leptin / Q000494:pharmacology; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D054369:Agouti-Related Protein; D020738:Leptin; D009478:Neuropeptide Y; D013973:Thyrotropin-Releasing Hormone