Title : Identification and characterization of
CTRP9 , a novel secreted
glycoprotein , from adipose tissue that reduces serum glucose in mice and forms heterotrimers with
adiponectin
Abstract :
- Adiponectin is a major insulin-sensitizing, multimeric hormone derived from adipose tissue that acts on muscle and liver to regulate whole-body glucose and lipid metabolism
- Here, we describe a novel and highly conserved paralog of adiponectin designated as C1q/TNF-related protein (CTRP) 9
- Of all the CTRP paralogs, CTRP9 shows the highest degree of amino acid identity to adiponectin in its globular C1q domain
- CTRP9 is expressed predominantly in adipose tissue and females expresses higher levels of the transcript than males
- Moreover, its expression levels in ob/ob mice changed in an age-dependent manner, with significant up-regulation in younger mice
- CTRP9 is a secreted glycoprotein with multiple post-translational modifications in its collagen domain that include hydroxylated prolines and hydroxylated and glycosylated lysines
- It is secreted as multimers (predominantly trimers) from transfected cells and circulates in the mouse serum with levels varying according to sex and metabolic state of mice
- Furthermore, CTRP9 and adiponectin can be secreted as heterooligomers when cotransfected into mammalian cells, and in vivo, adiponectin / CTRP9 complexes can be reciprocally coimmunoprecipitated from the serum of adiponectin and CTRP9 transgenic mice
- Biochemical analysis demonstrates that adiponectin and CTRP9 associate via their globular C1q domain , and this interaction does not require their conserved N-terminal cysteines or their collagen domains
- Furthermore, we show that adiponectin and CTRP9 form heterotrimers
- In cultured myotubes, CTRP9 specifically activates AMPK , Akt , and p44 /42 MAPK signaling pathways
- Adenovirus-mediated overexpression of CTRP9 in obese (ob/ob) mice significantly lowered serum glucose levels
- Collectively, these results suggest that CTRP9 is a novel adipokine, and further study of CTRP9 will yield novel mechanistic insights into its physiological and metabolic function
Output (sent_index, trigger,
protein,
sugar,
site):
- 0. glycoprotein, , CTRP9, -, -
- 0. glycoprotein, , glycoprotein, -, -
- 6. glycoprotein, , CTRP9, -, -
- 6. glycoprotein, , glycoprotein, -, -
- 6. glycosylated, , -, -, lysines
Output(Part-Of) (sent_index,
protein,
site):
- 3. C1q, domain
- 3. adiponectin, domain
- 9. C1q, domain
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):