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Departments of Psychology Columbia University (L.J.K. and R.S.) and Barnard College (R.S.) New York, New York 10027 and Department of Anatomy and Cell Biology (R.S.) College of Physicians and Surgeons New York, New York 10032
Address all correspondence and requests for reprints to: Rae Silver, Department of Psychology, Columbia University, 1190 Amsterdam Avenue, New York, New York 10027. E-mail: qr{at}columbia.edu.
OBESITY IS A GROWING health concern in the United States and abroad. Recent surveys indicate that approximately 30% of Americans are obese (body mass index > 30), with the prevalence of obesity having increased by approximately 60% over the last several decades (1). Obesity is associated with an increase in morbidity and mortality from a variety of health concerns including diabetes, cardiovascular disease, and respiratory disorders. Given these pronounced health problems in obese individuals and the growing trend in the United States, the current economic costs and predicted future costs of treating these patients is becoming a growing public concern.
Siberian hamsters (Phodopus sungorus sungorus) represent an excellent model for investigating the mechanisms regulating body weight and metabolic rate. Before winter, or following extended exposure to short-day lengths or melatonin, Siberian hamsters exhibit a pronounced decrease (
30%) in body weight (2, 3, 4, 5, 6). This decrease allows animals to survive challenging winter conditions by decreasing absolute energy requirements, thereby reducing foraging time and limiting exposure to inclement winter conditions (7). In Siberian hamsters, the decrease in body weight precedes a decrease in food intake, suggesting a metabolic basis for this reduction (8). Determining the mechanisms responsible for this dramatic body weight loss each year can aid in our understanding of the mechanisms responsible for regulating energy homeostasis and dysregulation.
In this issue of Endocrinology, Ross et al. (9) point to retinoid signaling as a potential neural mechanism underlying seasonal reductions in body weight in Siberian hamsters. As a point of comparison, the authors used Syrian hamsters (Mesocricetus auratus), a species that does not exhibit seasonal weight changes but does display seasonal pattern of reproduction similar to Siberian hamsters. The logic was that photoperiod-induced changes in genes in common between Siberian and Syrian hamsters may be involved in regulating reproductive responses to photoperiod, whereas divergent genes may be responsible for the dramatic weight changes seen in Siberian hamsters.
Some genes (RAR and CRBP1) in the retinoid signaling pathway are reduced in the dorsal tuberomammillary nucleus (DTM) of both Siberian and Syrian hamsters following short-day exposure. However, one of these genes, retinoid X receptor 
(RXR), is reduced in the DTM in Siberian but not Syrian hamsters following exposure to short days. Importantly, the reductions in gene expression seen following short-day exposure in Siberian hamsters are abolished by pinealectomy and are not affected by testosterone treatment, suggesting that the observed changes are driven by melatonin. In this study, dissection of the genes regulated in common in these two species, along with identification of divergent RXR expression patterns, revealed novel genes in the retinoid signaling pathway that may be involved in photoperiod-mediated changes in reproductive function (RAR and CRBP1) and energy balance (RXR). These data also implicate the DTM as an important locus for interpretation of photoperiodic information and for its subsequent relay to metabolic effector sites.
The retinoid X receptor (RXR) plays a crucial role in adipogenesis and insulin sensitization by binding to the nuclear hormone receptor, peroxisome proliferator-activated receptor (PPAR) (10, 11). PPARs are activated by fatty acids and fatty acid metabolites, placing this receptor complex in a unique position to act as a sensory system of the current energetic state of an organism. Data on the reductions in RXR seen the DTM of Siberian hamsters, combined with the known role of retinoid signaling in energy balance that parallel reductions in body weight, suggest an important role for this retinoid signaling in body weight regulation. The fact that Syrian hamsters do not exhibit photoperiod-induced changes in body weight or DTM RXR gene expression, adds another line of support for this hypothesis. Given that RXR::PPAR complexes act as transcription factors (11), identifying the downstream gene targets of this complex represents a window of opportunity in the search for novel factors regulating metabolism and body weight.
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Received October 7, 2003.
Accepted for publication October 8, 2003.
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 Top References |
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with body weight. Endocrinology 145:13–20. J Mol Med 79:30–47[CrossRef][Medline]
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