title: Reciprocal regulation of natriuretic peptide receptors by insulin in adipose cells.
abstract: Atrial- and brain-type natriuretic peptides (ANP and BNP, respectively) have been shown to exert potent lipolytic action in adipocytes. A family of natriuretic peptide receptors (NPRs), NPR-1, NPR-2, and NPR-3, mediates their physiologic effects. NPR-1 and NPR-2 are receptor guanylyl cyclases, while NPR-3 lacks enzymatic activity and functions primarily as a clearance receptor for natriuretic peptides. ANP has a high affinity for NPR-1 and NPR-3 than other natriuretic peptides. There is a possibility that ANP may exhibit its lipolytic effect through the balance of NPR-1 and NPR-3 expressions in adipocytes. However, the regulation of adipose NPRs has not been fully elucidated. We here examined the regulation of mouse adipose NPRs by insulin, an anti-lipolytic hormone. Among the insulin target organs, NPR-1 mRNA levels were higher in white adipose tissue (WAT) than in liver and skeletal muscle. NPR-3 mRNA was expressed most abundantly in WAT. Fasting condition induced NPR-1 mRNA level while suppressed NPR-3 mRNA level in WAT. Administration of streptozotocin resulted in the increase of NPR-1 mRNA level while the decrease of NPR-3 mRNA level in WAT. In ob/ob mice, hyperinsulinemic model, NPR-1 mRNA level was lower whereas NPR-3 mRNA level was higher compared to lean control mice. In 3T3-L1 adipocytes, insulin significantly reduced NPR-1 mRNA level while increased NPR-3 mRNA levels both through phosphatidylinositol 3-kinase (PI3-kinase) pathway. In summary, NPR-1 and NPR-3 were highly expressed in WAT and adipose NPR-1 and NPR-3 were reciprocally regulated by insulin. This study suggests that insulin may efficiently promote lipogenesis partly by reducing the lipolytic action of ANP through the opposite regulation of NPR-1 and NPR-3.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2-B5 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakatsuji
authors.forename: Norikazu
authors.initials: N
authors.lastname: Maeda
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hibuse
authors.forename: Aki
authors.initials: A
authors.lastname: Hiuge
authors.forename: Ayumu
authors.initials: A
authors.lastname: Hirata
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Ken
authors.initials: K
authors.lastname: Kishida
authors.forename: Shinji
authors.initials: S
authors.lastname: Kihara
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D050155:Lipogenesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism*; D013311:Streptozocin / Q000494:pharmacology; D014018:Tissue Distribution; D000099242:Atrial Natriuretic Factor Receptor B
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D017461:Receptors, Atrial Natriuretic Factor; D013311:Streptozocin; D000099242:Atrial Natriuretic Factor Receptor B; C058930:brain natriuretic peptide receptor; C091715:atrial natriuretic factor receptor A