title: Refeeding-induced brown adipose tissue glycogen hyper-accumulation in mice is mediated by insulin and catecholamines.
abstract: Brown adipose tissue (BAT) generates heat during adaptive thermogenesis through a combination of oxidative metabolism and uncoupling protein 1-mediated electron transport chain uncoupling, using both free-fatty acids and glucose as substrate. Previous rat-based work in 1942 showed that prolonged partial fasting followed by refeeding led to a dramatic, transient increase in glycogen stores in multiple fat depots. In the present study, the protocol was replicated in male CD1 mice, resulting in a 2000-fold increase in interscapular BAT (IBAT) glycogen levels within 4-12 hours (hr) of refeeding, with IBAT glycogen stores reaching levels comparable to fed liver glycogen. Lesser effects occurred in white adipose tissues (WAT). Over the next 36 hr, glycogen levels dissipated and histological analysis revealed an over-accumulation of lipid droplets, suggesting a potential metabolic connection between glycogenolysis and lipid synthesis. 24 hr of total starvation followed by refeeding induced a robust and consistent glycogen over-accumulation similar in magnitude and time course to the prolonged partial fast. Experimentation demonstrated that hyperglycemia was not sufficient to drive glycogen accumulation in IBAT, but that elevated circulating insulin was sufficient. Additionally, pharmacological inhibition of catecholamine production reduced refeeding-induced IBAT glycogen storage, providing evidence of a contribution from the central nervous system. These findings highlight IBAT as a tissue that integrates both canonically-anabolic and catabolic stimulation for the promotion of glycogen storage during recovery from caloric deficit. The preservation of this robust response through many generations of animals not subjected to food deprivation suggests that the over-accumulation phenomenon plays a critical role in IBAT physiology.
authors.affiliation: Committee on Molecular Metabolism and Nutrition, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Carmean
authors.forename: Alexandria M
authors.initials: AM
authors.lastname: Bobe
authors.forename: Justin C
authors.initials: JC
authors.lastname: Yu
authors.forename: Paul A
authors.initials: PA
authors.lastname: Volden
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Brady
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D004435:Eating; D004734:Energy Metabolism; D005215:Fasting; D006003:Glycogen / Q000096:biosynthesis*; D007328:Insulin / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D022722:Thermogenesis / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D002395:Catecholamines; D007328:Insulin; D006003:Glycogen