Identification of a biochemical link between energy intake and energy expenditure
Silvana Obici, … , Kimyata Morgan, Luciano Rossetti
Silvana Obici, … , Kimyata Morgan, Luciano Rossetti
Published June 15, 2002
Citation Information: J Clin Invest. 2002;109(12):1599-1605. https://doi.org/10.1172/JCI15258.
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Article Endocrinology

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

Silvana Obici, Jiali Wang, Rahena Chowdury, Zhaohui Feng, Uma Siddhanta, Kimyata Morgan, Luciano Rossetti

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Figure 1

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Activation of HBP increases O-linked glycosylation of nucleocytoplasmic ...
Activation of HBP increases O-linked glycosylation of nucleocytoplasmic proteins. (a) The enzyme OGTase links GlcNAc moieties to serine or threonine residues of transcriptional factors. O-GlcNAc induces conformational changes that render proteins refractory to proteosomal degradation and more available for modulation of transcription in the nucleus. (b) Schematic representation of experimental design. Acute infusion of glucosamine (30 μmol/kg/min) was performed during 4 hours of a hyperinsulinemic clamp involving the infusion of high-dose insulin (18 mU/kg/min) and glucose at variable rates to keep animals euglycemic. (c) Intracellular levels of UDP-GlcNAc in skeletal muscle of rats infused with saline (C) or glucosamine (G). *P < 0.005. (d) Western blot analysis of O-GlcNAc modification in skeletal muscle. Extracts from glucosamine-treated animals (G) and saline-infused animals (C) are compared.