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J Clin Invest. 2002 Jun;109(12):1599-605.

Identification of a biochemical link between energy intake and energy expenditure.

Author information

1
Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

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.

Comment in

PMID:
12070307
PMCID:
PMC151013
DOI:
10.1172/JCI15258
[Indexed for MEDLINE]
Free PMC Article

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