Leptin and thyrotropin-releasing hormone: cooperative action in the hindbrain to activate brown adipose thermogenesis.
Explanations of leptin induction of thermogenesis typically involve primary detection elements in the hypothalamus. In turn, these circuits control medullary raphe neurons that regulate spinal efferent sympathetic projections to heat-producing brown adipose tissue (BAT). The hindbrain may be capable of considerable thermoregulatory capacity independent of the hypothalamus, though little is known about the site(s), mechanism(s) of action, or the physiological consequences of leptin action in the hindbrain. Several reports describe the presence of leptin receptor in the solitary nucleus, and there is functional evidence that leptin can act in the dorsal medulla to suppress feeding. We examined the effects of leptin, applied to the dorsal medulla, on BAT thermogenesis. Leptin alone (< or =25 microg) had no independent effect on BAT thermogenesis. We hypothesized that, while leptin may not be capable of activating thermocontrol mechanisms in the hindbrain directly, it may modulate the efficacy of other neural signals involved in the control of thermogenesis such as thyrotropin-releasing hormone (TRH). We tested the hypothesis that leptin and TRH, acting in the hindbrain, co-regulate thermogenesis. As expected, TRH (0.1 microg), alone, produces a small increase (+0.75 degrees C) in BAT temperature. Co-application of leptin (5 mug) and TRH (0.1 microg) to the dorsal medulla produces an increase in BAT and core temperature more than 300% greater than TRH alone (+3.5 degrees C). This effect is undiminished in the acute decerebrate rat, suggesting that the effect is mediated entirely by the hindbrain.
Hermann
Gerlinda E
GE
Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Rd., Baton Rouge, Louisiana 70808, USA. HermanGE@pbrc.edu
Barnes
Maria J
MJ
Rogers
Richard C
RC
D002001:Adipose Tissue, Brown / Q000502:physiology*; D000818:Animals; D004347:Drug Interactions / Q000502:physiology; D004525:Efferent Pathways / Q000187:drug effects / Q000378:metabolism; D005260:Female; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009434:Neural Pathways / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012249:Rhombencephalon / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D022722:Thermogenesis / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology
D020738:Leptin; D013973:Thyrotropin-Releasing Hormone