Loss of CTRP4 alters adiposity and food intake behaviors in obese mice.

Central and peripheral mechanisms are both required for proper control of energy homeostasis. Among circulating plasma proteins, C1q/TNF-related proteins (CTRPs) have recently emerged as important regulators of sugar and fat metabolism. CTRP4, expressed in brain and adipose tissue, is unique among the family members in having two tandem globular C1q domains.

Protein Modifications Critical for Myonectin/Erythroferrone Secretion and Oligomer Assembly.

Myonectin/erythroferrone (also known as CTRP15) is a secreted hormone with metabolic function and a role in stress erythropoiesis. Despite its importance in physiologic processes, biochemical characterization of the protein is lacking. Here, we show that multiple protein modifications are critical for myonectin secretion and multimerization.

PRADC1: a novel metabolic-responsive secretory protein that modulates physical activity and adiposity.

Interorgan communication mediated by secreted proteins plays a pivotal role in metabolic homeostasis, yet the function of many circulating secretory proteins remains unknown. Here, we describe the function of protease-associated domain-containing 1 (PRADC1), an enigmatic secretory protein widely expressed in humans and mice. In metabolically active tissues (liver, muscle, fat, heart, and kidney), we showed that expression is significantly suppressed by refeeding and reduced in kidney and brown fat in the context of obesity.

Myonectin deletion promotes adipose fat storage and reduces liver steatosis.

We recently described myonectin (also known as erythroferrone) as a novel skeletal muscle-derived myokine with metabolic functions. Here, we use a genetic mouse model to determine myonectin's requirement for metabolic homeostasis. Female myonectin-deficient mice had larger gonadal fat pads and developed mild insulin resistance when fed a high-fat diet (HFD) and had reduced food intake during refeeding after an unfed period but were otherwise indistinguishable from wild-type littermates.

N-Linked Glycosylation-Dependent and -Independent Mechanisms Regulating CTRP12 Cleavage, Secretion, and Stability.

C1q/TNF-related protein 12 (CTRP12) is a secreted regulator of glucose and lipid metabolism. It circulates in plasma as a full-length protein or as a cleaved isoform generated by furin/PCSK3 cleavage. These isoforms preferentially activate different signaling pathways, and their ratio in plasma is altered in obesity and diabetes.