Effects of weight loss and leptin on skeletal muscle in human subjects

Am J Physiol Regul Integr Comp Physiol. 2011 Nov;301(5):R1259-66. doi: 10.1152/ajpregu.00397.2011. Epub 2011 Sep 14.


Maintenance of a 10% or greater reduced body weight results in decreases in the energy cost of low levels of physical activity beyond those attributable to the altered body weight. These changes in nonresting energy expenditure are due mainly to increased skeletal muscle work efficiency following weight loss and are reversed by the administration of the adipocyte-derived hormone leptin. We have also shown previously that the maintenance of a reduced weight is accompanied by a decrease in ratio of glycolytic (phosphofructokinase) to oxidative (cytochrome c oxidase) activity in vastus lateralis muscle that would suggest an increase in the relative expression of the myosin heavy chain I (MHC I) isoform. We performed analyses of vastus lateralis muscle needle biopsy samples to determine whether maintenance of an altered body weight was associated with changes in skeletal muscle metabolic properties as well as mRNA expression of different isoforms of the MHC and sarcoplasmic endoplasmic reticular Ca(2+)-dependent ATPase (SERCA) in subjects studied before weight loss and then again after losing 10% of their initial weight and receiving twice daily injections of either placebo or replacement leptin in a single blind crossover design. We found that the maintenance of a reduced body weight was associated with significant increases in the relative gene expression of MHC I mRNA that was reversed by the administration of leptin as well as an increase in the expression of SERCA2 that was not significantly affected by leptin. Leptin administration also resulted in a significant increase in the expression of the less MHC IIx isoform compared with subjects receiving placebo. These findings are consistent with the leptin-reversible increase in skeletal muscle chemomechanical work efficiency and decrease in the ratio of glycolytic/oxidative enzyme activities observed in subjects following dietary weight loss.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptation, Physiological
  • Adiposity
  • Analysis of Variance
  • Biopsy
  • Cross-Over Studies
  • Energy Metabolism / drug effects*
  • Female
  • Gene Expression Regulation
  • Humans
  • Injections, Subcutaneous
  • Leptin / administration & dosage*
  • Male
  • Muscle Contraction / drug effects
  • Muscle Strength / drug effects
  • Myosin Heavy Chains / genetics
  • Obesity / diet therapy*
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / pathology
  • Obesity / physiopathology
  • Quadriceps Muscle / drug effects*
  • Quadriceps Muscle / metabolism
  • Quadriceps Muscle / pathology
  • Quadriceps Muscle / physiopathology
  • RNA, Messenger / metabolism
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics
  • Single-Blind Method
  • Time Factors
  • Treatment Outcome
  • Weight Loss*


  • Leptin
  • RNA, Messenger
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Myosin Heavy Chains
  • ATP2A2 protein, human