title: 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.affiliation: Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. mr475@columbia.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Rosenbaum
authors.forename: Rochelle
authors.initials: R
authors.lastname: Goldsmith
authors.forename: Daniel
authors.initials: D
authors.lastname: Bloomfield
authors.forename: Anthony
authors.initials: A
authors.lastname: Magnano
authors.forename: Louis
authors.initials: L
authors.lastname: Weimer
authors.forename: Steven
authors.initials: S
authors.lastname: Heymsfield
authors.forename: Dympna
authors.initials: D
authors.lastname: Gallagher
authors.forename: Laurel
authors.initials: L
authors.lastname: Mayer
authors.forename: Ellen
authors.initials: E
authors.lastname: Murphy
authors.forename: Rudolph L
authors.initials: RL
authors.lastname: Leibel
mesh_terms: D000328:Adult; D001823:Body Composition; D015992:Body Mass Index; D001835:Body Weight; D002151:Calorimetry; D004038:Diet, Reducing; D002149:Energy Intake; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D020738:Leptin / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009490:Neurosecretory Systems; D009765:Obesity / Q000628:therapy; D010641:Phenotype; D013974:Thyroxine / Q000378:metabolism; D013997:Time Factors; D014284:Triiodothyronine / Q000378:metabolism; D015431:Weight Loss
chemical_list: D020738:Leptin; D014284:Triiodothyronine; D013974:Thyroxine