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Adropin: An endocrine link between the biological clock and cholesterol homeostasis.
Ghoshal, Sarbani; Stevens, Joseph R; Billon, Cyrielle; Girardet, Clemence; Sitaula, Sadichha; Leon, Arthur S; Rao, D C; Skinner, James S; Rankinen, Tuomo; Bouchard, Claude; Nuñez, Marinelle V; Stanhope, Kimber L; Howatt, Deborah A; Daugherty, Alan; Zhang, Jinsong; Schuelke, Matthew; Weiss, Edward P; Coffey, Alisha R; Bennett, Brian J; Sethupathy, Praveen; Burris, Thomas P; Havel, Peter J; Butler, Andrew A.
Afiliação
  • Ghoshal S; Department of Pharmacology and Physiology, Saint Louis University School of Medicine, Saint Louis University, St. Louis, MO, USA.
  • Stevens JR; Department of Pharmacology and Physiology, Saint Louis University School of Medicine, Saint Louis University, St. Louis, MO, USA.
  • Billon C; Department of Pharmacology and Physiology, Saint Louis University School of Medicine, Saint Louis University, St. Louis, MO, USA.
  • Girardet C; Department of Pharmacology and Physiology, Saint Louis University School of Medicine, Saint Louis University, St. Louis, MO, USA.
  • Sitaula S; Department of Pharmacology and Physiology, Saint Louis University School of Medicine, Saint Louis University, St. Louis, MO, USA.
  • Leon AS; School of Kinesiology and Leisure Studies, University of Minnesota, Minneapolis, MN, USA.
  • Rao DC; Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
  • Skinner JS; Department of Kinesiology, Indiana University, Bloomington, IN, USA.
  • Rankinen T; Human Genomics Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
  • Bouchard C; Human Genomics Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
  • Nuñez MV; Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA; Department of Nutrition, School of Medicine, University of California-Davis, Davis, CA, USA.
  • Stanhope KL; Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA; Department of Nutrition, School of Medicine, University of California-Davis, Davis, CA, USA.
  • Howatt DA; Saha Cardiovascular Research Center, Department of Physiology, University of Kentucky, KY, USA.
  • Daugherty A; Saha Cardiovascular Research Center, Department of Physiology, University of Kentucky, KY, USA.
  • Zhang J; Department of Pharmacology and Physiology, Saint Louis University School of Medicine, Saint Louis University, St. Louis, MO, USA.
  • Schuelke M; Department of Pharmacology and Physiology, Saint Louis University School of Medicine, Saint Louis University, St. Louis, MO, USA.
  • Weiss EP; Department of Nutrition and Dietetics, Doisy College of Health Sciences, Saint Louis University, St. Louis, MO, USA.
  • Coffey AR; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, USA.
  • Bennett BJ; Obesity and Metabolism Unit, Western Human Nutrition Center, USDA-ARS, Davis, CA, USA.
  • Sethupathy P; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
  • Burris TP; Department of Pharmacology and Physiology, Saint Louis University School of Medicine, Saint Louis University, St. Louis, MO, USA.
  • Havel PJ; Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA; Department of Nutrition, School of Medicine, University of California-Davis, Davis, CA, USA.
  • Butler AA; Department of Pharmacology and Physiology, Saint Louis University School of Medicine, Saint Louis University, St. Louis, MO, USA. Electronic address: Andrew.Butler@health.slu.edu.
Mol Metab ; 8: 51-64, 2018 02.
Article em En | MEDLINE | ID: mdl-29331507
OBJECTIVE: Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function. METHODS: Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico, in cultured human cells, and in animal models. RESULTS: In humans, plasma adropin concentrations are inversely related to atherogenic LDL-cholesterol (LDL-C) levels in men (n = 349), but not in women (n = 401). Analysis of hepatic Enho expression in male mice suggests control by the biological clock. Expression is rhythmic, peaking during maximal food consumption in the dark correlating with transcriptional activation by RORα/γ. The nadir in the light phase coincides with the rest phase and repression by Rev-erb. Plasma adropin concentrations in nonhuman primates (rhesus monkeys) also exhibit peaks coinciding with feeding times (07:00 h, 15:00 h). The ROR inverse agonists SR1001 and the 7-oxygenated sterols 7-ß-hydroxysterol and 7-ketocholesterol, or the Rev-erb agonist SR9009, suppress ENHO expression in cultured human HepG2 cells. Consumption of high-cholesterol diets suppress expression of the adropin transcript in mouse liver. However, adropin over expression does not prevent hypercholesterolemia resulting from a high cholesterol diet and/or LDL receptor mutations. CONCLUSIONS: In humans, associations between plasma adropin concentrations and LDL-C suggest a link with hepatic lipid metabolism. Mouse studies suggest that the relationship between adropin and cholesterol metabolism is unidirectional, and predominantly involves suppression of adropin expression by cholesterol and 7-oxygenated sterols. Sensing of fatty acids, cholesterol and oxysterols by the RORα/γ ligand-binding domain suggests a plausible functional link between adropin expression and cellular lipid metabolism. Furthermore, the nuclear receptors RORα/γ and Rev-erb may couple adropin synthesis with circadian rhythms in carbohydrate and lipid metabolism.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peptídeos / Proteínas / Relógios Circadianos / Homeostase / LDL-Colesterol Tipo de estudo: Prognostic_studies Limite: Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peptídeos / Proteínas / Relógios Circadianos / Homeostase / LDL-Colesterol Tipo de estudo: Prognostic_studies Limite: Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article