Silvana Obici, Jiali Wang, Rahena Chowdury, Zhaohui Feng, Uma Siddhanta, Kimyata Morgan, Luciano Rossetti
J Clin Invest.
2002;
109(12):1599–1605
doi:10.1172/JCI15258
This article Copyright © 2002, The American Society for Clinical Investigation
Abstract
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O
besity 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.
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