Leptin selectively decreases visceral adiposity and enhances insulin action

Nir Barzilai, Jiali Wang, Duna Massilon, Patricia Vuguin, Meredith Hawkins, Luciano Rossetti

Research output: Contribution to journalArticlepeer-review

297 Scopus citations


Intraabdominal adiposity and insulin resistance are risk factors for diabetes mellitus, dyslipidemia, arteriosclerosis, and mortality. Leptin, a fat-derived protein encoded by the ob gene, has been postulated to be a sensor of energy storage in adipose tissue capable of mediating a feedback signal to sites involved in the regulation of energy homeostasis. Here, we provide evidence for specific effects of leptin on fat distribution and in viva insulin action. Leptin (LEP) or vehicle (CON) was administered by osmotic minipumps for 8 d to pair-fed adult rats. During the 8 d of the study, body weight and total fat mass decreased similarly in LEP and in CON. However, while moderate calorie restriction (CON) resulted in similar decreases in whole body (by 20%) and visceral (by 21%) fat, leptin administration led to a specific and marked decrease (by 62%) in visceral adiposity. During physiologic hyperinsulinemia (insulin clamp), leptin markedly enhanced insulin action on both inhibition of hepatic glucose production and stimulation of glucose uptake. Finally, leptin exerted complex effects on the hepatic gene expression of key metabolic enzymes and on the intrahepatic partitioning of metabolic fluxes, which are likely to represent a defense against excessive storage of energy in adipose depots. These studies demonstrate novel actions of circulating leptin in the regulation of fat distribution, insulin action, and hepatic gene expression and suggest that it may play a role in the pathophysiology of abdominal obesity and insulin resistance.

Original languageEnglish (US)
Pages (from-to)3105-3110
Number of pages6
JournalJournal of Clinical Investigation
Issue number12
StatePublished - Dec 15 1997


  • Gluconeogenesis
  • Glucose uptake
  • Hepatic glucose production
  • Obesity

ASJC Scopus subject areas

  • Medicine(all)


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