Profound and rapid reduction in body temperature induced by the melanocortin receptor agonists

Abstract

The melanocortin receptor 4 (MC4R) plays a major role in body weight regulation and its agonist MTII has been widely used to study the role of MC4Rs in energy expenditure promotion and feeding reduction. Unexpectedly, we observed that intraperitoneal (i.p.) administration of MTII induced a rapid reduction in both body temperature and energy expenditure, which was independent of its effect on feeding and followed by a prolonged increase in energy expenditure. The rapid reduction was at least partly mediated by brain neurons since intracerebroventricular (icv) administration of alpha melanocyte-stimulating hormone, an endogenous melanocortin receptor agonist, produced a similar response. In addition, the body temperature-lowering effect of MTII was independent of the presence of MC4Rs, but in a similar fashion to the previously shown effect on body temperature by 5′AMP. Moreover, β-adrenergic receptors (β-ARs) were required for the recovery from low body temperature induced by MTII and further pharmacological studies showed that the MTII’s effect on body temperature may be partially mediated by the vasopressin V1a receptors. Collectively, our results reveal a previously unappreciated role for the melanocortin pathway in rapidly lowering body temperature.

The Role of the Melanocortin System in Metabolic Disease: New Developments and Advances

“…The latter seems to be independent of MC4Rs and possibly dependent on a similar biphasic effect on heart rate [190, 191]. BAT plays a crucial role in adaptive thermogenesis in response to diet or environmental challenges.…”

Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of oxytocin-elicited reductions of body weight and adiposity in male diet-induced obese mice

“…Similar to systemic OT, we and others have demonstrated that systemic MTII produces an initial reduction of T IBAT and/or core temperature [85; 86] followed by a subsequent elevation of T IBAT or core temperature [86]. Like OT, MTII-elicited reduction of body temperature was found to be blunted in response to the AVPR1A antagonist [85]. In addition to a mechanism involving AVPV1A, MTII-elicited hypothermia is also due, in part, to mast cell activation [87].…”

“…Kohli reported that pretreatment with arginine vasopressin receptor 1A (AVPR1A) antagonist can reduce OT-mediated hypothermia, while pretreatment with OTR antagonist does not [84]. Similar to systemic OT, we and others have demonstrated that systemic MTII produces an initial reduction of T IBAT and/or core temperature [85; 86] followed by a subsequent elevation of T IBAT or core temperature [86]. Like OT, MTII-elicited reduction of body temperature was found to be blunted in response to the AVPR1A antagonist [85].…”

Red blood cell β-adrenergic receptors contribute to diet-induced energy expenditure by increasing O2 supply

“…Samples of mixed arterial and vein blood were collected from tails using a capillary collection device (ITC International) as previously reported (50). Blood samples were transferred to cuvettes (ITC International) immediately, and the levels of O 2 contents, O 2 -Hb, and total Hb were measured using whole blood oximeter (Avoximeter 1000E, ITC International).…”