Moreover, these more physiologically relevant MEL signals reduce body fat (WAT mass) equivalent to that seen with transfer from LDs to SDs ( 7, 25) however, reductions in WAT mass have not, to our knowledge, been assessed using the timed MEL injection model.īecause MEL is unable to stimulate white adipocyte lipolysis directly ( 26), we reasoned that MEL may be having its effects on lipid mobilization via a secondary hormone. Collectively it is the duration of the MEL signal that is important for inducing SD responses once a threshold value has been reached or exceeded ( 23, 24). Even though such timed MEL injections produce nonphysiological circulating concentrations of MEL, the SD-like responses are quite similar to that achieved with timed daily MEL sc infusions in pinealectomized Siberian hamsters that mimic SD nocturnal durations of the hormone and that create circulating MEL concentrations that are physiological (for review see Ref. Specifically, timed systemic injections of MEL occurring about 3–4 h before lights off in LD-housed, pineal-intact hamsters generate a MEL signal that summates with the naturally occurring, short nocturnal duration of MEL secretion associated with LDs, thereby lengthening it and triggering SD responses in Siberian hamsters ( 22). These and other SD responses are triggered by decreases in the daylength naturally ( 17, 18) that can be mimicked in the laboratory by decreases in the vivarium photoperiod ( 19) or by manipulating the neuroendocrine transducer of the seasonal photoperiod information, the duration of the nocturnal secretion of melatonin. By contrast, in short winter-like days (SDs), the LD responses are reversed, exhibiting profound decreases in body mass and fat (∼−30%), testicular regression, marked increases in thermogenic responses (nonshivering thermogenesis), expression of shallow daily torpor, change to a white-winter pelage color (for review see Refs. In long summer-like days (LDs), Siberian hamsters accrue large amounts of lipid reserves, are reproductively active, and have unremarkable thermogenic responses (for review see Refs. Siberian hamsters provide an ideal model to study the natural reversal of obesity because it is a seasonal animal and exhibits a suite of responses governed by the photoperiod. The precise mechanisms underlying the latter are less well defined, especially concerning lipid mobilization, although increases in the sympathetic nervous system (SNS) drive to white adipose tissue (WAT) is the principal initiator of lipolysis (for review see Refs. Whereas the development of obesity results from increased food intake and/or decreased energy expenditure, the opposite holds true for its reversal. Obesity is one of the fastest growing health threats in America, promoting secondary health consequences such as stroke, cardiovascular disease, certain types of cancer, and diabetes mellitus ( e.g. Collectively these data suggest a distributed system of MEL-sensitive brain sites sufficient to mediate these SD responses, the redundancy of which suggests its importance for appropriate seasonal responses critical for overwintering. Third ventricle, sc, suprachiasmatic nucleus, or SubZi MEL application also decreased WAT mass, and only sc and SubZi MEL application decreased food intake.
Whereas SD MEL signals delivered to each of these sites were able to induce testicular regression, all but the paraventricular nuclei of the thalamus also trigger SD-induced decreases in body mass. A long duration, SD-like MEL signal was applied site specifically for 5 wk, with sc and third ventricle MEL application serving as positive controls. We tested the involvement of these sites in MEL-triggered SD responses. WAT is innervated by the sympathetic nervous system, and several forebrain sites that are part of the sympathetic nervous system outflow to WAT coexpress MEL 1a receptor mRNA.
The pineal hormone melatonin (MEL) is the key initiator in regulating seasonal photoperiodic responses however, the central sites that mediate short day (SD) winter-like responses, such as testicular regression and decreases in white adipose tissue (WAT) mass, by Siberian hamsters are not precisely known.