Leptin is required for uncoupling protein-1-independent thermogenesis during cold stress.
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.
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, 70808, USA.
Jozef
J
Ukropec
Rea V P
RV
Anunciado
Yann
Y
Ravussin
Leslie P
LP
Kozak
D020155:3-Hydroxybutyric Acid / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001831:Body Temperature; D001835:Body Weight; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002151:Calorimetry; D002352:Carrier Proteins / Q000378:metabolism*; D003080:Cold Temperature; D005260:Female; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007473:Ion Channels; D020738:Leptin / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins; D009154:Mutation; D010101:Oxygen Consumption; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013696:Temperature; D013963:Thyroid Hormones / Q000378:metabolism; D013997:Time Factors; D014284:Triiodothyronine / Q000378:metabolism; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D007328:Insulin; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D013963:Thyroid Hormones; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D014284:Triiodothyronine; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D005947:Glucose; D020155:3-Hydroxybutyric Acid