Leptin Raises Defended Body Temperature without Activating Thermogenesis

• Published in: Cell reports (Cambridge) 2016-02, Vol.14 (7), p.1621-1631
• Main Authors: Fischer, Alexander W., Hoefig, Carolin S., Abreu-Vieira, Gustavo, de Jong, Jasper M.A., Petrovic, Natasa, Mittag, Jens, Cannon, Barbara, Nedergaard, Jan
• Format: Article
• Language: English
• Subjects: Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - metabolism; Adipose Tissue, White - drug effects; Adipose Tissue, White - metabolism; Adrenergic beta-3 Receptor Agonists - pharmacology; Animals; Body Temperature - drug effects; Body Temperature - genetics; Dioxoles - pharmacology; Eating - drug effects; Energy Metabolism - drug effects; Energy Metabolism - genetics; Gene Expression Regulation; Leptin - genetics; Leptin - metabolism; Leptin - pharmacology; Male; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Mice, Transgenic; Obesity - genetics; Obesity - metabolism; Obesity - pathology; Tail - drug effects; Tail - metabolism; Thermogenesis - drug effects; Thermogenesis - genetics
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.01.041

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. [Display omitted] •ob/ob mice are not hypometabolic and do not have reduced BAT thermogenic capacity•ob/ob mice are not hypothermic but display downward shift in thermoregulatory thresholds•Leptin is not thermogenic and does not increase BAT recruitment•Leptin is pyrexic and increases body temperature by reducing heat loss Leptin is thought to reduce body weight by both reducing food intake and increasing brown adipose tissue (BAT) thermogenesis. In the present study, Fischer et al. show that leptin does not affect BAT thermogenesis; instead, it leads to a pyrexic increase in body temperature by reducing heat loss.