Leptin Resistance During Aging Is Independent of Fat Mass

  1. Ilan Gabriely12,
  2. Xiao Hui Ma12,
  3. Xiao Man Yang12,
  4. Luciano Rossetti1 and
  5. Nir Barzilai12
  1. 1Department of Medicine, Division of Endocrinology, Diabetes Research and Training Center
  2. 2Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York


    Increased fat mass, abdominal adiposity, and insulin resistance are typical findings in aging mammals and are frequently associated with leptin resistance and increased plasma leptin levels. To examine whether leptin’s failure in aging is due to aging per se or to changes in body fat mass or distribution, we studied aging rats that underwent calorie restriction throughout their lives, maintaining their youthful body fat pattern and metabolic profile. Leptin’s action was assessed by measuring its ability to regulate food intake, fat mass and its distribution, peripheral and hepatic insulin action, and its own gene expression in fat. Our results show that leptin’s action is markedly diminished in aging rats, independently of their body fat pattern. Leptin’s failure in this model suggests its causative role in the metabolic decline seen with aging.


    • Address correspondence and reprint requests to Nir Barzilai, Institute for Aging Research, 1300 Morris Park Ave., Belfer Bldg. #701, Bronx, NY 10461. E-mail: barzilai{at}aecom.yu.edu.

      Received for publication 13 September 2001 and accepted in revised form 17 December 2001.

      G.I. and X.H.M. contributed equally to this work.

      ds, double-stranded; EGP, endogenous glucose production; FFA, free fatty acid; FM, fat mass; NS, normal saline; PF, pair-fed; SOCS-3, suppressor of cytokine signaling 3; TG, triglyceride; VF, visceral fat.

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