{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:07:18Z","timestamp":1790478438933,"version":"4.1.0"},"reference-count":242,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:p>Orexin A and B are two neuropeptides, which regulate a variety of physiological functions by interacting with central nervous system and peripheral tissues. Biological effects of orexins are mediated through two G-protein-coupled receptors (OXR1 and OXR2). In addition to their strong influence on the sleep\u2013wake cycle, there is growing evidence that orexins regulate body weight, glucose homeostasis and insulin sensitivity. Furthermore, orexins promote energy expenditure and protect against obesity by interacting with brown adipocytes. Fat tissue and the endocrine pancreas play pivotal roles in maintaining energy homeostasis. Since both organs are crucially important in the context of pathophysiology of obesity and diabetes, we summarize the current knowledge regarding the role of orexins and their receptors in controlling adipocytes as well as the endocrine pancreatic functions. Particularly, we discuss studies evaluating the effects of orexins in controlling brown and white adipocytes as well as pancreatic alpha and beta cell functions.<\/jats:p>","DOI":"10.1530\/joe-18-0122","type":"journal-article","created":{"date-parts":[[2018,5,30]],"date-time":"2018-05-30T10:00:20Z","timestamp":1527674420000},"page":"R95-R108","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":19,"title":["The role of orexin in controlling the activity of the adipo-pancreatic axis"],"prefix":"10.1530","volume":"238","author":[{"given":"M","family":"Skrzypski","sequence":"first","affiliation":[{"name":"1Department of Animal Physiology and Biochemistry, Pozna\u0144 University of Life Sciences, Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Billert","sequence":"additional","affiliation":[{"name":"1Department of Animal Physiology and Biochemistry, Pozna\u0144 University of Life Sciences, Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K W","family":"Nowak","sequence":"additional","affiliation":[{"name":"1Department of Animal Physiology and Biochemistry, Pozna\u0144 University of Life Sciences, Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Z","family":"Strowski","sequence":"additional","affiliation":[{"name":"2Department of Hepatology and Gastroenterology & The Interdisciplinary Centre of Metabolism: Endocrinology, Diabetes and Metabolism, Charit\u00e9-University Medicine Berlin, Berlin, Germany"},{"name":"3Park-Klinik Weissensee, Internal Medicine \u2013 Gastroenterology, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref841","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0092-8674(00)80949-6","article-title":"Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled 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of pancreatic beta - cell death in type type diabetes many differences few similarities Supplement https org","year":"2005","journal-title":"Diabetes"},{"key":"ref741","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1038\/ijo.2017.155","article-title":"Investigating the effects of Orexin-A on thermogenesis in human deep neck brown adipose tissue","volume":"41","year":"2017","journal-title":"International Journal of Obesity"},{"key":"ref2401","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1093\/abbs\/gmq010","article-title":"Prevention of diet-induced obesity by safflower oil: insights at the levels of PPARalpha, orexin, and ghrelin gene expression of adipocytes in mice","volume":"42","year":"2010b","journal-title":"Acta Biochimica et Biophysica Sinica"},{"key":"ref831","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0167-0115(01)00349-4","article-title":"Chronic intraparaventricular nuclear administration of orexin A in male rats does not alter 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of leptin, ghrelin, angiotensin II and orexins in 3T3 L1 preadipocyte cells proliferation and oxidative metabolism","volume":"58","year":"2007","journal-title":"Journal of Physiology and Pharmacology"},{"key":"ref871","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s12944-015-0123-1","article-title":"The role of fatty acids in insulin resistance","volume":"14","year":"2015","journal-title":"Lipids in Health and Disease"},{"key":"ref1021","first-page":"211","article-title":"Effect of diet-induced weight loss on inflammatory cytokines in obese women","volume":"36","year":"2013","journal-title":"Journal of Endocrinological Investigation"},{"key":"ref701","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1007\/s00125-015-3573-0","article-title":"Orexin A regulates plasma insulin and leptin levels in a time-dependent manner following a glucose load in 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