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Orexin A-induced inhibition of leptin expression and secretion in adipocytes reducing plasma leptin levels and hypothalamic leptin resistance.
Shin, Su-Kyung; Song, Seung-Eun; Oh, Jin Uk; Hwang, Meeyul; Cho, Hyun-Woo; Bae, Jae-Hoon; Im, Seung-Soon; Kim, Jee-In; Song, Dae-Kyu.
Afiliação
  • Shin SK; Department of Physiology, Keimyung University School of Medicine, 1095 Dalgubeoldae-Ro, Dalseo-Gu, Daegu, 42601, South Korea.
  • Song SE; Department of Physiology, Keimyung University School of Medicine, 1095 Dalgubeoldae-Ro, Dalseo-Gu, Daegu, 42601, South Korea.
  • Oh JU; Department of Physiology, Keimyung University School of Medicine, 1095 Dalgubeoldae-Ro, Dalseo-Gu, Daegu, 42601, South Korea.
  • Hwang M; Department of Physiology, Keimyung University School of Medicine, 1095 Dalgubeoldae-Ro, Dalseo-Gu, Daegu, 42601, South Korea.
  • Cho HW; Department of Physiology, Keimyung University School of Medicine, 1095 Dalgubeoldae-Ro, Dalseo-Gu, Daegu, 42601, South Korea.
  • Bae JH; Department of Physiology, Keimyung University School of Medicine, 1095 Dalgubeoldae-Ro, Dalseo-Gu, Daegu, 42601, South Korea.
  • Im SS; Department of Physiology, Keimyung University School of Medicine, 1095 Dalgubeoldae-Ro, Dalseo-Gu, Daegu, 42601, South Korea.
  • Kim JI; Department of Molecular Medicine, Keimyung University School of Medicine, 1095 Dalgubeoldae-Ro, Dalseo-Gu, Daegu, 42601, Korea.
  • Song DK; Department of Physiology, Keimyung University School of Medicine, 1095 Dalgubeoldae-Ro, Dalseo-Gu, Daegu, 42601, South Korea. dksong@kmu.ac.kr.
Pflugers Arch ; 471(11-12): 1407-1418, 2019 12.
Article em En | MEDLINE | ID: mdl-31667577
ABSTRACT
Orexin A (OXA) is a neuropeptide associated with plasma insulin and leptin levels involved in body weight and appetite regulation. However, little is known about the effect of OXA on leptin secretion in adipocytes and its physiological roles. Leptin secretion and expression were analysed in 3T3-L1 adipocytes. Plasma leptin, adiponectin and insulin levels were measured by ELISA assay. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3) levels in the hypothalamus were evaluated by western blotting. OXA dose-dependently suppressed leptin secretion from 3T3-L1 adipocytes by inhibiting its gene expression while facilitating adiponectin secretion. The leptin inhibition by OXA was mediated via orexin receptors (OXR1 and OXR2). In addition to the pathway via extracellular signal-regulated kinases, OXA triggered adenylyl cyclase-induced cAMP elevation, which results in protein kinase A-mediated activation of cAMP response element-binding proteins (CREB). Accordingly, CREB inhibition restored the OXA-induced downregulation of leptin gene expression and secretion. Exogenous OXA for 4 weeks decreased fasting plasma leptin levels and increased hypothalamic pSTAT3 levels in high-fat diet-fed mice, regardless of increase in body weight and food intake. These results suggest that high dose of OXA directly inhibits leptin mRNA expression and thus secretion in adipocytes, which may be a peripheral mechanism of OXA for its role in appetite drive during fasting. It may be also critical for lowering basal plasma leptin levels and thus maintaining postprandial hypothalamic leptin sensitivity.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Adipócitos / Leptina / Orexinas / Hipotálamo Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Adipócitos / Leptina / Orexinas / Hipotálamo Idioma: En Ano de publicação: 2019 Tipo de documento: Article