A nutrient-sensing pathway regulates leptin gene expression in muscle and fat

J. Wang, R. Liu, Meredith A. Hawkins, Nir Barzilai, L. Rossetti

Research output: Contribution to journalArticle

639 Citations (Scopus)

Abstract

Leptin, the protein encoded by the obese (ob) gene, is synthesized and released in response to increased energy storage in adipose tissue1-4. However, it is still not known how incoming energy is sensed and transduced into increased expression of the ob gene. The hexosamine biosynthetic pathway is a cellular 'sensor' of energy availability5-8 and mediates the effects of glucose on the expression of several gene products9-12. Here we provide evidence for rapid activation of ob gene expression in skeletal muscle by glucosamine. Increased tissue concentrations of the end product of the hexosamine biosynthetic pathway, UDP-N-acetylglucosamine (UDP-GlcNAc), result in rapid and marked increases in leptin messenger RNA and protein levels (although these levels were much lower than those in fat). Plasma leptin levels and leptin mRNA and protein levels in adipose tissue also increase. Most important, stimulation of leptin synthesis is reproduced by either hyperglycaemia or hyperlipidaemia, which also increase tissue levels of UDP- N-acetylglucosamine in conscious rodents7. Finally, incubation of 3T3-L1 pre- adipocytes and L6 myocytes with glucosamine rapidly induces ob gene expression. Our findings are the first evidence of inducible leptin expression in skeletal muscle and unveil an important biochemical link between increased availability of nutrients and leptin expression.

Original languageEnglish (US)
Pages (from-to)684-688
Number of pages5
JournalNature
Volume393
Issue number6686
DOIs
StatePublished - Jun 18 1998

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Leptin
Fats
Gene Expression
Food
Muscles
Uridine Diphosphate N-Acetylglucosamine
Hexosamines
Glucosamine
Biosynthetic Pathways
Skeletal Muscle
Messenger RNA
Uridine Diphosphate
Hyperlipidemias
Adipocytes
Hyperglycemia
Muscle Cells
Adipose Tissue
Proteins
Glucose
Genes

ASJC Scopus subject areas

  • General

Cite this

A nutrient-sensing pathway regulates leptin gene expression in muscle and fat. / Wang, J.; Liu, R.; Hawkins, Meredith A.; Barzilai, Nir; Rossetti, L.

In: Nature, Vol. 393, No. 6686, 18.06.1998, p. 684-688.

Research output: Contribution to journalArticle

Wang, J. ; Liu, R. ; Hawkins, Meredith A. ; Barzilai, Nir ; Rossetti, L. / A nutrient-sensing pathway regulates leptin gene expression in muscle and fat. In: Nature. 1998 ; Vol. 393, No. 6686. pp. 684-688.
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