Skeletal bone morphology is resistant to the high amplitude seasonal leptin cycle in the Siberian hamster.

Recent studies have suggested that the adipocyte-derived hormone, leptin, plays a role in the regulation of metabolism. Here, we tested this hypothesis in the seasonally breeding Siberian hamster, as this species exhibits profound seasonal changes in adiposity and circulating leptin concentrations driven by the annual photoperiodic cycle. Male hamsters were kept in either long (LD) or short (SD) photoperiods. Following exposure to short photoperiods for 8 weeks animals exhibited a significant weight-loss and a 16-fold reduction of serum leptin concentrations. At Week 9, animals in both photoperiods were infused with leptin or PBS via osmotic mini-pump for 14 days. Chronic leptin infusion mimicked LD-like concentrations in SD-housed animals and caused a further decline in body weight and adipose tissue. In LD-housed animals, leptin infusion resulted in a significant elevation of serum concentrations above natural LD-like levels, but had no discernable effect on body weight or overall adiposity. Both bending and compression characteristics and histomorphometric measurements of trabecular bone mass were unaltered by leptin treatment or photoperiod. Our data therefore show that despite a high natural amplitude cycle of leptin, this hormone has no apparent role in the regulation of bone metabolism, and therefore do not support recent propositions that this hormone is an important component in the metabolism of bone tissue.

Leptin and seasonal mammals.

Seasonal mammals commonly exhibit robust annual cycles of adiposity, food intake and energy metabolism. These cycles are driven by changes in the external daylength signal, which generates a diurnal melatonin profile and acts on neuroendocrine pathways. The white adipose tissue hormone leptin reflects overall adiposity in seasonal mammals, and consequently undergoes significant seasonal fluctuations in secretion. The seasonally breeding Siberian (Djungarian) hamster is a convenient laboratory model to study the effect of a seasonal time-keeping clock on energy metabolism, appetite regulation and the control of adiposity. We have shown that administration of exogenous leptin at physiological doses induces significant loss of adipose tissue for short-day housed winter-like hamsters in which endogenous adipose tissue and leptin concentrations are already low. By contrast, long-day housed hamsters with high adipose tissue reserves are refractory to the effects of leptin. This phenomenon of seasonal leptin resistance appears to be a general feature of other seasonally breeding mammals, and may reflect the operation of an annual timer controlling leptin uptake and/or action on central nervous system signal transduction pathways. The mobilization of fat by leptin in short-day housed hamsters is not associated with changes in expression in either anorexic or anabolic peptides expressed in leptin-receptor rich structures in the arcuate region of the hypothalamus, and suggests that leptin may target other structures. These data contrast with studies, which show that homeostatic mechanisms in response to feed-restriction induce changes in hypothalamic peptides in a similar manner to nonphotoperiodic species. Thus, the long-term seasonal regulation of body weight set point and leptin feedback may operate through separate pathways to those responsible for acute responses to food restriction.

Leptin acts on metabolism in a photoperiod-dependent manner, but has no effect on reproductive function in the seasonally breeding Siberian hamster (Phodopus sungorus).

Leptin may play a role in appetite regulation and metabolism, but its reproductive role is less clear. In photoperiodic Siberian hamsters, seasonal changes in fatness, leptin gene expression, and metabolism occur synchronously with activation or suppression of reproduction, analogous to puberty. Here, we test the hypothesis that seasonal changes in leptin secretion mediate the photoperiodic regulation of reproduction. Mature male and ovariectomized estrogen-treated female Siberian hamsters were kept in long (LD; 16 h of light, 8 h of darkness) or short days (SD; 8 h of light, 16 h of darkness) for 8 weeks, and recombinant murine leptin (15 microg/day) was infused for 2 weeks via osmotic minipumps. SD hamsters exhibited significant weight and fat losses, reduced serum leptin and food intake, and suppressed pituitary LH concentration. Leptin did not suppress food intake over the 2-week treatment on either photoperiod, but significantly reduced fat reserves in SD hamsters. Leptin had no significant effect on pituitary LH concentrations in either sex or photoperiod or on testicular size and testosterone concentrations in males. These results suggest hamsters are more responsive to leptin on SD than on LD and that effects on food intake and fat loss can be dissociated in this species. Our data suggest that leptin does not mediate photoperiodic reproductive changes.