Effects of leptin replacement alone and with exendin-4 on food intake and weight regain in weight-reduced diet-induced obese rats

Roger Reidelberger, Alvin Haver, Prasanth K. Chelikani, Bettye Apenteng, Curtis Perriotte-Olson, Krista Anders, Sharalyn Steenson, James E. Blevins

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Weight loss in obese humans produces a relative leptin deficiency, which is postulated to activate potent orexigenic and energy conservation mechanisms to restrict weight loss and promote weight regain. Here we determined whether leptin replacement alone or with GLP-1 receptor agonist exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced diet-induced obese (DIO) rats. Forty percent restriction in daily intake of a high-fat diet in DIO rats for 4 wk reduced body weight by 12%, body fat by 29%, and plasma leptin by 67% and normalized leptin sensitivity. When food restriction ended, body weight, body fat, and plasma leptin increased rapidly. Daily administration of leptin [3-h intraperitoneal (ip) infusions (4 nmol·kg _1·h -1)] at onset and end of dark period for 3 wk did not attenuate hyperphagia and weight regain, nor did it affect mean daily meal sizes or meal numbers. Exendin-4 (50 pmol·kg _1·h _1) infusions during the same intervals prevented postrestriction hyperphagia and weight regain by normalizing meal size. Coadministration of leptin and exendin-4 did not reduce body weight more than exendin-4 alone. Instead, leptin began to attenuate the inhibitory effects of exendin-4 on food intake, meal size, and weight regain by the end of the second week of administration. Plasma leptin in rats receiving leptin was sevenfold greater than in rats receiving vehicle and 17-fold greater than in rats receiving exendin-4. Together, these results do not support the hypothesis that leptin replacement alone or with exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced DIO rats.

Original languageEnglish
Pages (from-to)E1576-E1585
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume302
Issue number12
DOIs
StatePublished - Jun 15 2012

Scopus Subject Areas

  • General Medicine

Keywords

  • Food restriction
  • Glucagon-like peptide-1 receptor agonist
  • Hyperphagia
  • Leptin sensitivity

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