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.
View: Text | PDF
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

×

Figure 4

Options: View larger image (or click on image) Download as PowerPoint
Energy expenditure and skeletal muscle. Percent change (mean ± SEM) from...
Energy expenditure and skeletal muscle. Percent change (mean ± SEM) from values at Wtinitial of energy expenditure, skeletal muscle work efficiency, and fuel utilization. Administration of leptin to weight-reduced subjects reversed the significant decline in TEE and NREE associated with maintenance of a 10% reduced body weight. Effects of weight loss and exogenous leptin on skeletal muscle gross mechanical work efficiency (kcal/min energy expended above resting per kcal/min work generated) and fuel utilization (derived from RQ; ref. 87) were only evident at low levels of work (bicycling to generate 10 W of power). Mean ± SEM values at each weight plateau are presented in Supplemental Table 1, and individual values are presented in Supplemental Figure 1. *P < 0.05 versus 0; †P < 0.05 versus Wt–10%. GME, gross mechanical efficiency.