title: C1q/TNF-related protein 4 (CTRP4) is a unique secreted protein with two tandem C1q domains that functions in the hypothalamus to modulate food intake and body weight.
abstract: CTRP4 is a unique member of the C1q family, possessing two tandem globular C1q domains. Its physiological function is poorly defined. Here, we show that CTRP4 is an evolutionarily conserved, ∼34-kDa secretory protein expressed in the brain. In human, mouse, and zebrafish brain, CTRP4 expression begins early in development and is widespread in the central nervous system. Neurons, but not astrocytes, express and secrete CTRP4, and secreted proteins form higher-order oligomeric complexes. CTRP4 is also produced by peripheral tissues and circulates in blood. Its serum levels are increased in leptin-deficient obese (ob/ob) mice. Functional studies suggest that CTRP4 acts centrally to modulate energy metabolism. Refeeding following an overnight fast induced the expression of CTRP4 in the hypothalamus. Central administration of recombinant protein suppressed food intake and altered the whole-body energy balance in both chow-fed and high-fat diet-fed mice. Suppression of food intake by CTRP4 is correlated with a decreased expression of orexigenic neuropeptide (Npy and Agrp) genes in the hypothalamus. These results establish CTRP4 as a novel nutrient-responsive central regulator of food intake and energy balance.
authors.affiliation: From the Departments of Physiology.
authors.forename: Mardi S
authors.initials: MS
authors.lastname: Byerly
authors.forename: Pia S
authors.initials: PS
authors.lastname: Petersen
authors.forename: Santosh
authors.initials: S
authors.lastname: Ramamurthy
authors.forename: Marcus M
authors.initials: MM
authors.lastname: Seldin
authors.forename: Xia
authors.initials: X
authors.lastname: Lei
authors.forename: Elayne
authors.initials: E
authors.lastname: Provost
authors.forename: Zhikui
authors.initials: Z
authors.lastname: Wei
authors.forename: Gabriele V
authors.initials: GV
authors.lastname: Ronnett
authors.forename: G William
authors.initials: GW
authors.lastname: Wong
mesh_terms: D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D054369:Agouti-Related Protein / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001835:Body Weight / Q000502:physiology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004435:Eating / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D051379:Mice; D009478:Neuropeptide Y / Q000096:biosynthesis / Q000235:genetics; D017434:Protein Structure, Tertiary; D051381:Rats; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*
chemical_list: C515198:AGRP protein, human; C515197:AGRP protein, rat; D054392:Adipokines; D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; C560750:C1QTNF4 protein, human; C000621233:Ctrp4 protein, mouse; D016207:Cytokines; D009478:Neuropeptide Y
keywords: Energy Metabolism; Hormones; Hypothalamus; Metabolism; Neuropeptide; Obesity