No abstract

Thermoregulation is a physiological process by which a mammal regulates body temperature in response to its environment. Within the human body, thermoregulatory behaviors and metabolism are modulated by circulating metabolic factors. In our study, we tested the ability of the neuropeptide spexin, which shares sequence homology to galanin, to regulate these functions in female mice. Supraphysiological levels of spexin in C57BL/6 mice were insufficient to protect against diet-induced obesity after 50 days of treatment. Behavioral analysis of long-term spexin treatment appeared to modulate anxiety-like behaviors by promoting exploratory behaviors and thermoregulatory behaviors of nest building that ceased when animals were housed at thermoneutral temperatures. Upon examination of the molecular profile of brown and white adipose tissue, treatment disrupted the thermogenic profile of white adipose tissue, in which β3-adrenergic receptor expression was downregulated. Our results reveal novel functions for spexin as a modulator of thermoregulatory behaviors and adipose tissue metabolism.

In the last decade, neuropeptide Q or spexin (SPX) was implicated in central and peripheral functions including feeding suppression and lipid metabolism. To test whether spexin acts on brown and white adipose tissue, we performed subcutaneous micro-osmotic infusion of spexin in mice with diet-induced obesity. Our preliminary results indicate that spexin may differentially regulate biomarkers of adipogenesis and insulin sensitivity in brown and white adipose tissue. Spexin infusion increased interscapular brown adipose tissue mass and mRNA expression of adiponectin, fatty-acid binding protein 4, lipoprotein lipase, and C/EBP-⍺ in female C57BL/6 mice. Within gonadal white adipose tissue, spexin and PPAR-γ2 mRNA expression was upregulated while immunohistochemistry of gWAT revealed that β3-adrenergic receptor expression was significantly decreased while adipocyte diameter was increased. These results indicate that spexin infusion differentially regulates adipogenesis within brown adipose tissue by increasing BAT mass and increasing non-adrenergic regulation of adipogenesis within gonadal white adipose tissue.