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

TLDR

Reduced weight maintenance is linked to lower energy expenditure, higher skeletal muscle efficiency, and diminished sympathetic tone and thyroid hormones, resembling leptin‑deficient conditions. The study examined ten subjects under three conditions—maintaining usual weight, a 10 % weight loss, and leptin replacement to pre‑loss levels while keeping the 10 % loss—to assess metabolic, autonomic, and neuroendocrine responses. Leptin replacement restored energy expenditure, muscle work efficiency, sympathetic tone, and thyroid hormones to pre‑loss levels, suggesting that the weight‑reduced state reflects relative leptin insufficiency and that correcting this may prevent weight regain.

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.