Overfeeding rapidly induces leptin and insulin resistance

Jiali Wang, Silvana Obici, Kimyata Morgan, Nir Barzilai, Zhaohui Feng, Luciano Rossetti

Research output: Contribution to journalArticlepeer-review

274 Scopus citations


In common forms of obesity, hyperphagia, hyperinsulinemia, and hyperleptinemia coexist. Here, we demonstrate rapid induction of insulin and leptin resistance by short-term overfeeding. After 3 and 7 days on the assigned diet regimen, rats were tested for their biological responses to acute elevations in plasma insulin and leptin concentrations. Severe resistance to the metabolic effects of both leptin and insulin ensued after just 3 days of overfeeding. During the insulin clamp studies, glucose production was decreased by ∼70% in control rats and 28-53% in overfed rats. Similarly, leptin infusion doubled the contribution of gluconeogenesis to glucose output in control rats but failed to modify gluconeogenesis in overfed animals. These findings demonstrate a paradoxical and rapid collapse of the leptin system in response to nutrient excess. This partial failure is tightly coupled with the onset of insulin resistance.

Original languageEnglish (US)
Pages (from-to)2786-2791
Number of pages6
Issue number12
StatePublished - Dec 2001

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


Dive into the research topics of 'Overfeeding rapidly induces leptin and insulin resistance'. Together they form a unique fingerprint.

Cite this