Leptin potentiates thermogenic sympathetic responses to hypothermia: a receptor-mediated effect.
Leptin contributes to the regulation of thermogenesis. In rodents, sympathetic nerve activity efferent to interscapular brown adipose tissue (IBAT-SNA) is involved. On the basis of the hypotheses that 1) leptin acutely potentiates hypothermia-induced increases in IBAT-SNA; 2) this action of leptin is specific to IBAT-SNA, i.e., it does not occur with renal sympathetic nerve activity (R-SNA); and 3) this effect of leptin depends on intact and functional leptin receptors, we measured IBAT-SNA and R-SNA in anesthetized lean and diet-induced obese Sprague-Dawley and in obese Zucker rats, randomly assigned to low-dose leptin or vehicle. Before the start of leptin or vehicle and 5 min, 90 min, and 180 min after, hypothermia (30 degrees C) was induced. Compared with vehicle, leptin did not significantly alter baseline R-SNA or IBAT-SNA. In lean Sprague-Dawley rats, hypothermia-induced increases in IBAT-SNA were significantly augmented by leptin but not by vehicle. In obese Sprague-Dawley rats, leptin did not potentiate hypothermia-induced increases in IBAT-SNA. In Zucker rats, IBAT-SNA did not increase with hypothermia and leptin was not able to induce sympathoactivation with cooling. Changes in R-SNA during hypothermia were not significantly modified by leptin in either group. Thus, low-dose leptin, although not altering baseline SNA, acutely enhances hypothermia-induced sympathetic outflow to IBAT in lean rats. This effect is specific for thermogenic SNA because leptin does not significantly alter the response of R-SNA to hypothermia. The effect depends on intact and functional leptin receptors because it occurs neither in rats with a leptin receptor defect nor in rats with acquired leptin resistance.
Hausberg
Martin
M
Department of Internal Medicine D, University of Muenster, Muenster, Germany.
Morgan
Donald A
DA
Mitchell
Jennifer L
JL
Sivitz
William I
WI
Mark
Allyn L
AL
Haynes
William G
WG
D002001:Adipose Tissue, Brown / Q000294:innervation / Q000502:physiology* / Q000503:physiopathology; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D007035:Hypothermia / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D008954:Models, Biological; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology
D002352:Carrier Proteins; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin