title: Identification of a biochemical link between energy intake and energy expenditure.
abstract: Obesity is the result of an imbalance between energy intake and energy expenditure. Using high-density DNA microarrays and Northern analyses, we demonstrated that the activation of a nutrient-sensing pathway, the hexosamine biosynthesis pathway (HBP), rapidly decreased the expression of a cluster of nuclear-encoded mitochondrial genes involved in skeletal muscle oxidative phosphorylation. Conversely, the expression of uncoupling protein-1 and of the same mitochondrial genes was increased in brown adipose tissue. Most important, these transcriptional changes were accompanied by a marked decrease in whole-body energy expenditure. Short-term overfeeding replicated this transcriptional pattern, suggesting that this adaptation to nutrient abundance occurs under physiological conditions. Thus, the activation of the HBP by nutrients represents a biochemical link between nutrient availability, mitochondrial proteins, and energy expenditure, and it is likely to play an important role in the regulation of energy balance.
authors.affiliation: Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Silvana
authors.initials: S
authors.lastname: Obici
authors.forename: Jiali
authors.initials: J
authors.lastname: Wang
authors.forename: Rahena
authors.initials: R
authors.lastname: Chowdury
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Feng
authors.forename: Uma
authors.initials: U
authors.lastname: Siddhanta
authors.forename: Kimyata
authors.initials: K
authors.lastname: Morgan
authors.forename: Luciano
authors.initials: L
authors.lastname: Rossetti
mesh_terms: D000818:Animals; D015536:Down-Regulation; D002149:Energy Intake; D004734:Energy Metabolism / Q000502:physiology*; D015870:Gene Expression; D005944:Glucosamine / Q000008:administration & dosage; D006595:Hexosamines / Q000096:biosynthesis*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000378:metabolism
chemical_list: D006595:Hexosamines; D014537:Uridine Diphosphate N-Acetylglucosamine; D005944:Glucosamine