Abstract
C1q/TNF-related protein 13 (CTRP13), a hormone secreted by adipose tissue (adipokines), helps regulate glucose metabolism in peripheral tissues. We previously reported that CTRP13 expression is increased in obese and hyperphagic leptin-deficient mice, suggesting that it may modulate food intake and body weight. CTRP13 is also expressed in the brain, although its role in modulating whole-body energy balance remains unknown. Here, we show that CTRP13 is a novel anorexigenic factor in the mouse brain. Quantitative PCR demonstrated that food restriction downregulates Ctrp13 expression in mouse hypothalamus, while high-fat feeding upregulates expression. Central administration of recombinant CTRP13 suppressed food intake and reduced body weight in mice. Further, CTRP13 and the orexigenic neuropeptide agouti-related protein (AgRP) reciprocally regulate each other’s expression in the hypothalamus: central delivery of CTRP13 suppressed Agrp expression, while delivery of AgRP increased Ctrp13 expression. Food restriction alone reduced Ctrp13 and increased orexigenic neuropeptide gene (Npy and Agrp) expression in the hypothalamus; in contrast, when food restriction was coupled to enhanced physical activity in an activity-based anorexia (ABA) mouse model, hypothalamic expression of both Ctrp13 and Agrp were upregulated. Taken together, these results suggest that CTRP13 and AgRP form a hypothalamic feedback loop to modulate food intake and that this neural circuit may be disrupted in an anorexic-like condition.
Highlights
The hypothalamus plays a central role in integrating hormonal and neural signaling pathways to modulate food intake and body weight [1]
Ctrp13 transcript levels were measured in the central nervous system (CNS), the hypothalamus, under metabolic stress induced by high-fat feeding in DIO mice
Given the importance of the hypothalamus in controlling food intake and peripheral energy metabolism [1], this result suggests that hypothalamic expression of Ctrp13 may be physiologically relevant in the context of food intake and body weight regulation
Summary
The hypothalamus plays a central role in integrating hormonal and neural signaling pathways to modulate food intake and body weight [1]. Neurons in the arcuate nucleus respond to leptin, a hormone secreted by adipocytes (known as an adipokine) in proportion to fat mass, to suppress food intake [2]. Individuals diagnosed with the eating disorder anorexia nervosa (AN) have increased circulating levels of AgRP [3,4], and a polymorphism in the coding region of AgRP is associated with AN [5]. Leptin and another widely-studied adipokine, adiponectin, act in the hypothalamus to regulate body weight [6,7,8]. Plasma leptin levels decrease in an anorexic state [9], while circulating levels of adiponectin vary depending on the type of AN [10,11,12,13]
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