Leptin selectively reduces white adipose tissue in mice via a UCP1-dependent mechanism in brown adipose tissue.
We tested the hypothesis that leptin, in addition to reducing body fat by restraining food intake, reduces body fat through a peripheral mechanism requiring uncoupling protein 1 (UCP1). Leptin was administered to wild-type (WT) mice and mice with a targeted disruption of the UCP1 gene (UCP1 deficient), while vehicle-injected control animals of each genotype were pair-fed to each leptin-treated group. Leptin reduced the size of white adipose tissue (WAT) depots in WT mice but not in UCP1-deficient animals. This was accompanied by a threefold increase in the amount of UCP1 protein and mRNA in the brown adipose tissue (BAT) of WT mice. Leptin also increased UCP2 mRNA in WAT of both WT and UCP1-deficient mice but increased UCP2 and UCP3 mRNA only in BAT from UCP1-deficient mice. These results indicate that leptin reduces WAT through a peripheral mechanism requiring the presence of UCP1, with little or no involvement of UCP2 or UCP3.
Commins
S P
SP
Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Watson
P M
PM
Frampton
I C
IC
Gettys
T W
TW
D000273:Adipose Tissue / Q000033:anatomy & histology* / Q000187:drug effects* / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004435:Eating / Q000187:drug effects; D004822:Epididymis; D007473:Ion Channels; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D026901:Membrane Transport Proteins; D051379:Mice; D024101:Mitochondrial Proteins; D009929:Organ Size / Q000187:drug effects; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; C000604372:Ucp1 protein, mouse; C000604390:Ucp2 protein, mouse; C000604393:Ucp3 protein, mouse; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3