Hypothalamic resistin induces hepatic insulin resistance

Evan D. Muse, Tony K T Lam, Philipp E. Scherer, Luciano Rossetti

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Circulating resistin stimulates endogenous glucose production (GP). Here, we report that bi-directional changes in hypothalamic resistin action have dramatic effects on GP and proinflammatory cytokine expression in the liver. The infusion of either resistin or an active cysteine mutant in the third cerebral ventricle (icv) or in the mediobasal hypothalamus stimulated GP independent of changes in circulating levels of glucoregulatory hormones. Conversely, central antagonism of resistin action markedly diminished the ability of circulating resistin to enhance GP. We also report that centrally mediated mechanisms partially control resistin-induced expression of TNF-α, IL-6, and SOCS-3 in the liver. These results unveil what we believe to be a novel site of action of resistin on GP and inflammation and suggest that hypothalamic resistin action can contribute to hyperglycemia in type 2 diabetes mellitus.

Original languageEnglish (US)
Pages (from-to)1670-1678
Number of pages9
JournalJournal of Clinical Investigation
Volume117
Issue number6
DOIs
StatePublished - Jun 1 2007

Fingerprint

Resistin
Insulin Resistance
Liver
Glucose
Cerebral Ventricles
Third Ventricle
Hyperglycemia
Type 2 Diabetes Mellitus
Hypothalamus
Cysteine
Interleukin-6
Hormones
Cytokines
Inflammation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hypothalamic resistin induces hepatic insulin resistance. / Muse, Evan D.; Lam, Tony K T; Scherer, Philipp E.; Rossetti, Luciano.

In: Journal of Clinical Investigation, Vol. 117, No. 6, 01.06.2007, p. 1670-1678.

Research output: Contribution to journalArticle

Muse, Evan D. ; Lam, Tony K T ; Scherer, Philipp E. ; Rossetti, Luciano. / Hypothalamic resistin induces hepatic insulin resistance. In: Journal of Clinical Investigation. 2007 ; Vol. 117, No. 6. pp. 1670-1678.
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