Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight
Michael Rosenbaum, … , Ellen Murphy, Rudolph L. Leibel
Michael Rosenbaum, … , Ellen Murphy, Rudolph L. Leibel
Published December 1, 2005
Citation Information: J Clin Invest. 2005;115(12):3579-3586. https://doi.org/10.1172/JCI25977.
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Research Article Metabolism

Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight

Abstract

Maintenance of a reduced body weight is accompanied by decreased energy expenditure that is due largely to increased skeletal muscle work efficiency. In addition, decreased sympathetic nervous system tone and circulating concentrations of leptin, thyroxine, and triiodothyronine act coordinately to favor weight regain. These “weight-reduced” phenotypes are similar to those of leptin-deficient humans and rodents. We examined metabolic, autonomic, and neuroendocrine phenotypes in 10 inpatient subjects (5 males, 5 females [3 never-obese, 7 obese]) under 3 sets of experimental conditions: (a) maintaining usual weight by ingesting a liquid formula diet; (b) maintaining a 10% reduced weight by ingesting a liquid formula diet; and (c) receiving twice-daily subcutaneous doses of leptin sufficient to restore 8 am circulating leptin concentrations to pre–weight-loss levels and remaining on the same liquid formula diet required to maintain a 10% reduced weight. During leptin administration, energy expenditure, skeletal muscle work efficiency, sympathetic nervous system tone, and circulating concentrations of thyroxine and triiodothyronine returned to pre–weight-loss levels. These responses suggest that the weight-reduced state may be regarded as a condition of relative leptin insufficiency. Prevention of weight regain might be achievable by strategies relevant to reversing this leptin-insufficient state.

Authors

Michael Rosenbaum, Rochelle Goldsmith, Daniel Bloomfield, Anthony Magnano, Louis Weimer, Steven Heymsfield, Dympna Gallagher, Laurel Mayer, Ellen Murphy, Rudolph L. Leibel

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Effects of weight loss and leptin administration on circulating leptin c...
Effects of weight loss and leptin administration on circulating leptin concentrations. (A) 8 am plasma leptin concentrations at Wtinitial, Wt–10%, and Wt–10%lep. Circulating leptin concentrations were significantly lower at Wt–10%, than at Wtinitial or at Wt–10%lep. (B) Percent changes (mean ± SEM) from Wtinitial values in plasma leptin concentrations at Wt–10% and Wt–10%lep. *P < 0.05 compared with 0.