Identification of a biochemical link between energy intake and energy expenditure

• Published in: The Journal of clinical investigation 2002-06, Vol.109 (12), p.1599-1605
• Main Authors: Obici, Silvana, Wang, Jiali, Chowdury, Rahena, Feng, Zhaohui, Siddhanta, Uma, Morgan, Kimyata, Rossetti, Luciano
• Format: Article
• Language: English
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI15258

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.