Leptin is required for uncoupling protein-1-independent thermogenesis during cold stress

Endocrinology. 2006 May;147(5):2468-80. doi: 10.1210/en.2005-1216. Epub 2006 Feb 9.


We investigated the role of leptin in regulating energy metabolism through induction of uncoupling protein (UCP)-1-based brown fat thermogenesis by comparing phenotypes of energy balance in ob/ob and double-mutant ob/ob.Ucp1(-/-) mice. Measurements of adiposity and lean body mass (nuclear magnetic resonance), energy expenditure (indirect calorimetry), body weight, food intake, and core body temperature were determined in the two mutant stocks of 3-month-old mice maintained at an initial ambient temperature of 28 C for 21 d and then at 21 C for 16 d, and finally with leptin administration for 8 d at 21 C. No phenotypic differences between ob/ob and ob/ob.Ucp1(-/-) mice were detected, suggesting that UCP1-based thermogenesis is not essential for the regulation of adiposity in ob/ob mice at temperatures between 21 and 28 C. Although both Ucp1(-/-) and ob/ob mice can survive in extreme cold at 4 C, provided they are adapted to the cold by gradually lowering ambient temperature, ob/ob.Ucp1(-/-) mice could not adapt and survive at temperatures lower than 12 C unless they were administered leptin. As the ambient temperature was reduced from 20 to 16 C, ob/ob.Ucp1(-/-) mice treated with leptin have elevated levels of circulating T(3) that correlate with elevated sarcoendoplasmic reticulum Ca(2+) ATPase 2a mRNA levels in gastrocnemius muscle. Furthermore, ob/ob.Ucp1(-/-) mice, treated with T(3), were able to maintain body temperature and stimulate sarcoendoplasmic reticulum Ca(2+) ATPase 2a expression when the ambient temperature was gradually reduced to 4 C. Thus, in the absence of UCP1, leptin-induced thermogenesis protects body temperature in part through its action on the thyroid hormone axis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3-Hydroxybutyric Acid / metabolism
  • Adipose Tissue / metabolism
  • Animals
  • Body Temperature
  • Body Weight
  • Calcium-Transporting ATPases / metabolism
  • Calorimetry
  • Carrier Proteins / metabolism*
  • Cold Temperature
  • Female
  • Gene Expression Regulation
  • Glucose / metabolism
  • Insulin / metabolism
  • Ion Channels
  • Leptin / metabolism*
  • Male
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mitochondrial Proteins
  • Mutation
  • Oxygen Consumption
  • Phenotype
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Temperature
  • Thyroid Hormones / metabolism
  • Time Factors
  • Triiodothyronine / metabolism
  • Uncoupling Protein 1


  • Carrier Proteins
  • Insulin
  • Ion Channels
  • Leptin
  • Membrane Proteins
  • Mitochondrial Proteins
  • Thyroid Hormones
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Triiodothyronine
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium-Transporting ATPases
  • Glucose
  • 3-Hydroxybutyric Acid