Identification of a biochemical link between energy intake and energy expenditure.
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.
Obici
Silvana
S
Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Wang
Jiali
J
Chowdury
Rahena
R
Feng
Zhaohui
Z
Siddhanta
Uma
U
Morgan
Kimyata
K
Rossetti
Luciano
L
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
D006595:Hexosamines; D014537:Uridine Diphosphate N-Acetylglucosamine; D005944:Glucosamine