title: Leptin Raises Defended Body Temperature without Activating Thermogenesis.
abstract: Leptin has been believed to exert its weight-reducing action not only by inducing hypophagia but also by increasing energy expenditure/thermogenesis. Leptin-deficient ob/ob mice have correspondingly been thought to be thermogenically limited and to show hypothermia, mainly due to atrophied brown adipose tissue (BAT). In contrast to these established views, we found that BAT is fully functional and that leptin treatment did not increase thermogenesis in wild-type or in ob/ob mice. Rather, ob/ob mice showed a decreased but defended body temperature (i.e., were anapyrexic, not hypothermic) that was normalized to wild-type levels after leptin treatment. This was not accompanied by increased energy expenditure or BAT recruitment but, instead, was mediated by decreased tail heat loss. The weight-reducing hypophagic effects of leptin are, therefore, not augmented through a thermogenic effect of leptin; leptin is, however, pyrexic, i.e., it alters centrally regulated thresholds of thermoregulatory mechanisms, in parallel to effects of other cytokines.
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, 10691 Stockholm, Sweden; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Fischer
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
authors.forename: Carolin S
authors.initials: CS
authors.lastname: Hoefig
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, 10691 Stockholm, Sweden.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Abreu-Vieira
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, 10691 Stockholm, Sweden.
authors.forename: Jasper M A
authors.initials: JMA
authors.lastname: de Jong
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, 10691 Stockholm, Sweden.
authors.forename: Natasa
authors.initials: N
authors.lastname: Petrovic
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Mittag
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, 10691 Stockholm, Sweden.
authors.forename: Barbara
authors.initials: B
authors.lastname: Cannon
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, 10691 Stockholm, Sweden. Electronic address: jan@metabol.su.se.
authors.forename: Jan
authors.initials: J
authors.lastname: Nedergaard
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects* / Q000235:genetics; D004149:Dioxoles / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation; D020738:Leptin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013623:Tail / Q000187:drug effects / Q000378:metabolism; D022722:Thermogenesis / Q000187:drug effects* / Q000235:genetics
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D004149:Dioxoles; D020738:Leptin; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate