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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

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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 2

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In vivo effect of GlcN on the expression of nuclear-encoded mitochondria...
In vivo effect of GlcN on the expression of nuclear-encoded mitochondrial transcripts. (a) Schematic illustration of respiratory chain complexes and oxidative phosphorylation. Electrons (e–) donated from fuel oxidation are sequentially transferred from ubiquinone (Q and QH2) to cytochrome c (Cyt. c), and finally to oxygen (O2). Simultaneously, protons (H+) are translocated across the inner mitochondrial membrane and create an electrochemical gradient whose energy is eventually used by ATP synthase for ATP formation. An adenine nucleotide translocator (ANT) carries ATP out of the mitochondria in exchange for ADP. The complexes indicated in gray contain one or more subunits downregulated by glucosamine. COX, cytochrome c oxidase; SDH, succinate dehydrogenase. (b) Northern analysis of mitochondrial transcripts in skeletal muscle from glucosamine versus saline infusion (control) with probes encoding mitochondrial malate dehydrogenase, NADH dehydrogenase, cytochrome c oxidase (COX-VIB), ATP synthase, and β-actin. (c) Quantitation, by densitometry, of Northern blots shown in b. Data are expressed as percent of control hybridization and are normalized with a β-actin probe. (d) Northern analysis of mitochondrial transcripts in BAT from glucosamine versus saline infusion (control) studies. Probes are the same as in b, except for the BAT-selective UCP-1. (e) Quantitation of Northern blot shown in d. Legend to bar graphs: Black, control; dark gray, UCP-1; medium gray, ATP synthase; white, cytochrome c oxidase VIB; light gray, NADH dehydrogenase; hatched, malate dehydrogenase. *P < 0.01.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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