A central role for C1q/TNF-related protein 13 (CTRP13) in modulating food intake and body weight

• Published in: PloS one Vol. 8; no. 4; p. e62862
• Main Authors: Byerly, Mardi S, Swanson, Roy, Wei, Zhikui, Seldin, Marcus M, McCulloh, Patrick S, Wong, G William
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.04.2013; Public Library of Science (PLoS)
• Subjects: Adipocytes; Adipokines - genetics; Adipokines - metabolism; Adipokines - pharmacology; Adipose tissue; Agouti-related protein; Agouti-Related Protein - metabolism; Animal tissues; Animals; Anorexia; Anorexia - metabolism; Anorexia - physiopathology; Anorexia nervosa; Anorexia Nervosa - metabolism; Anorexia Nervosa - physiopathology; Biology; Body weight; Body Weight - drug effects; Brain; Brain research; Diet - adverse effects; Eating - drug effects; Eating disorders; Energy balance; Exercise; Fatty acids; Feedback loops; Food; Food availability; Food intake; Gene expression; Glucose metabolism; HEK293 Cells; Hormones - genetics; Hormones - metabolism; Hormones - pharmacology; Humans; Hypothalamus; Hypothalamus - drug effects; Hypothalamus - metabolism; Laboratory animals; Leptin; Male; Medical research; Medicine; Metabolism; Mice; Mice, Inbred C57BL; Neural circuitry; Neuropeptide Y; Neuropeptides; Neuropeptides - metabolism; Nutrition research; Obesity; Obesity - etiology; Obesity - genetics; Phenotype; Physical activity; Physiological aspects; Physiology; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Studies; Twins; Weight reduction; United States > US; Maryland; Baltimore Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0062862

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.