CONTEXT: CCAAT/enhancer binding protein alpha (C/EBPalpha) is a transcription factor involved in adipogenesis and hepatic glucose and lipid metabolism. OBJECTIVE: The aim of the study was to test the hypothesis that adipose tissue C/EBPalpha regulates genes in lipid and glucose metabolism and to test for an association between a polymorphism in C/EBPalpha and metabolic parameters. DESIGN AND METHODS: Adipose tissue C/EBPalpha mRNA expression was analyzed at four time points in obese subjects with (n = 12) and without (n = 12) the metabolic syndrome during caloric restriction (450 kcal/d for 16 wk) using DNA microarray and real-time PCR. Adenoviral overexpression of C/EBPalpha was used to identify genes regulated by C/EBPalpha in 3T3-L1 cells. Association between a genetic variation in C/EBPalpha (rs12691) and metabolic parameters was tested in the Swedish Obese Subjects (SOS) study (n = 528) and replicated in Finnish individuals from the Botnia type 2 diabetes study (n = 4,866). RESULTS: During caloric restriction, adipose tissue C/EBPalpha mRNA levels were reduced in subjects with the metabolic syndrome (P = 0.024) and correlated to metabolic parameters. In 3T3-L1 cells, C/EBPalpha regulated the expression of adiponectin; hexokinase 2; lipoprotein lipase; diacylglycerol O-acyltransferase 1 and 2; ATP-binding cassette, sub-family D, member 2; acyl-coenzyme A synthetase long-chain family member 1; CD36; and hydroxysteroid 11-beta dehydrogenase 1. Furthermore, the expression of the human homologs, except adiponectin, correlated to C/EBPalpha mRNA levels in human adipose tissue. The AA genotype of rs12691 was associated with higher serum triglyceride levels in the SOS study (P = 0.022), and this association was replicated in the Botnia study (P = 0.041). CONCLUSIONS: Adipose tissue C/EBPalpha regulates several genes in glucose and lipid metabolism, and a genetic variation in C/EBPalpha is associated with triglycerides in two independent populations.
CONTEXT: CCAAT/enhancer binding protein alpha (C/EBPalpha) is a transcription factor involved in adipogenesis and hepatic glucose and lipid metabolism. OBJECTIVE: The aim of the study was to test the hypothesis that adipose tissue C/EBPalpha regulates genes in lipid and glucose metabolism and to test for an association between a polymorphism in C/EBPalpha and metabolic parameters. DESIGN AND METHODS: Adipose tissue C/EBPalpha mRNA expression was analyzed at four time points in obese subjects with (n = 12) and without (n = 12) the metabolic syndrome during caloric restriction (450 kcal/d for 16 wk) using DNA microarray and real-time PCR. Adenoviral overexpression of C/EBPalpha was used to identify genes regulated by C/EBPalpha in 3T3-L1 cells. Association between a genetic variation in C/EBPalpha (rs12691) and metabolic parameters was tested in the Swedish Obese Subjects (SOS) study (n = 528) and replicated in Finnish individuals from the Botnia type 2 diabetes study (n = 4,866). RESULTS: During caloric restriction, adipose tissue C/EBPalpha mRNA levels were reduced in subjects with the metabolic syndrome (P = 0.024) and correlated to metabolic parameters. In 3T3-L1 cells, C/EBPalpha regulated the expression of adiponectin; hexokinase 2; lipoprotein lipase; diacylglycerol O-acyltransferase 1 and 2; ATP-binding cassette, sub-family D, member 2; acyl-coenzyme A synthetase long-chain family member 1; CD36; and hydroxysteroid 11-beta dehydrogenase 1. Furthermore, the expression of the human homologs, except adiponectin, correlated to C/EBPalpha mRNA levels in human adipose tissue. The AA genotype of rs12691 was associated with higher serum triglyceride levels in the SOS study (P = 0.022), and this association was replicated in the Botnia study (P = 0.041). CONCLUSIONS: Adipose tissue C/EBPalpha regulates several genes in glucose and lipid metabolism, and a genetic variation in C/EBPalpha is associated with triglycerides in two independent populations.
Authors: Samuel W Caito; Jennifer Newell-Caito; Megan Martell; Nicole Crawford; Michael Aschner Journal: Toxicol Sci Date: 2020-03-01 Impact factor: 4.849
Authors: Daniel A Dumesic; Ayli Tulberg; Karen L Leung; Samantha C Fisch; Tristan R Grogan; David H Abbott; Rajanigandha Naik; Gregorio D Chazenbalk Journal: Fertil Steril Date: 2020-12-17 Impact factor: 7.490
Authors: Robert A Scott; Vasiliki Lagou; Ryan P Welch; Eleanor Wheeler; May E Montasser; Jian'an Luan; Reedik Mägi; Rona J Strawbridge; Emil Rehnberg; Stefan Gustafsson; Stavroula Kanoni; Laura J Rasmussen-Torvik; Loïc Yengo; Cecile Lecoeur; Dmitry Shungin; Serena Sanna; Carlo Sidore; Paul C D Johnson; J Wouter Jukema; Toby Johnson; Anubha Mahajan; Niek Verweij; Gudmar Thorleifsson; Jouke-Jan Hottenga; Sonia Shah; Albert V Smith; Bengt Sennblad; Christian Gieger; Perttu Salo; Markus Perola; Nicholas J Timpson; David M Evans; Beate St Pourcain; Ying Wu; Jeanette S Andrews; Jennie Hui; Lawrence F Bielak; Wei Zhao; Momoko Horikoshi; Pau Navarro; Aaron Isaacs; Jeffrey R O'Connell; Kathleen Stirrups; Veronique Vitart; Caroline Hayward; Tõnu Esko; Evelin Mihailov; Ross M Fraser; Tove Fall; Benjamin F Voight; Soumya Raychaudhuri; Han Chen; Cecilia M Lindgren; Andrew P Morris; Nigel W Rayner; Neil Robertson; Denis Rybin; Ching-Ti Liu; Jacques S Beckmann; Sara M Willems; Peter S Chines; Anne U Jackson; Hyun Min Kang; Heather M Stringham; Kijoung Song; Toshiko Tanaka; John F Peden; Anuj Goel; Andrew A Hicks; Ping An; Martina Müller-Nurasyid; Anders Franco-Cereceda; Lasse Folkersen; Letizia Marullo; Hanneke Jansen; Albertine J Oldehinkel; Marcel Bruinenberg; James S Pankow; Kari E North; Nita G Forouhi; Ruth J F Loos; Sarah Edkins; Tibor V Varga; Göran Hallmans; Heikki Oksa; Mulas Antonella; Ramaiah Nagaraja; Stella Trompet; Ian Ford; Stephan J L Bakker; Augustine Kong; Meena Kumari; Bruna Gigante; Christian Herder; Patricia B Munroe; Mark Caulfield; Jula Antti; Massimo Mangino; Kerrin Small; Iva Miljkovic; Yongmei Liu; Mustafa Atalay; Wieland Kiess; Alan L James; Fernando Rivadeneira; Andre G Uitterlinden; Colin N A Palmer; Alex S F Doney; Gonneke Willemsen; Johannes H Smit; Susan Campbell; Ozren Polasek; Lori L Bonnycastle; Serge Hercberg; Maria Dimitriou; Jennifer L Bolton; Gerard R Fowkes; Peter Kovacs; Jaana Lindström; Tatijana Zemunik; Stefania Bandinelli; Sarah H Wild; Hanneke V Basart; Wolfgang Rathmann; Harald Grallert; Winfried Maerz; Marcus E Kleber; Bernhard O Boehm; Annette Peters; Peter P Pramstaller; Michael A Province; Ingrid B Borecki; Nicholas D Hastie; Igor Rudan; Harry Campbell; Hugh Watkins; Martin Farrall; Michael Stumvoll; Luigi Ferrucci; Dawn M Waterworth; Richard N Bergman; Francis S Collins; Jaakko Tuomilehto; Richard M Watanabe; Eco J C de Geus; Brenda W Penninx; Albert Hofman; Ben A Oostra; Bruce M Psaty; Peter Vollenweider; James F Wilson; Alan F Wright; G Kees Hovingh; Andres Metspalu; Matti Uusitupa; Patrik K E Magnusson; Kirsten O Kyvik; Jaakko Kaprio; Jackie F Price; George V Dedoussis; Panos Deloukas; Pierre Meneton; Lars Lind; Michael Boehnke; Alan R Shuldiner; Cornelia M van Duijn; Andrew D Morris; Anke Toenjes; Patricia A Peyser; John P Beilby; Antje Körner; Johanna Kuusisto; Markku Laakso; Stefan R Bornstein; Peter E H Schwarz; Timo A Lakka; Rainer Rauramaa; Linda S Adair; George Davey Smith; Tim D Spector; Thomas Illig; Ulf de Faire; Anders Hamsten; Vilmundur Gudnason; Mika Kivimaki; Aroon Hingorani; Sirkka M Keinanen-Kiukaanniemi; Timo E Saaristo; Dorret I Boomsma; Kari Stefansson; Pim van der Harst; Josée Dupuis; Nancy L Pedersen; Naveed Sattar; Tamara B Harris; Francesco Cucca; Samuli Ripatti; Veikko Salomaa; Karen L Mohlke; Beverley Balkau; Philippe Froguel; Anneli Pouta; Marjo-Riitta Jarvelin; Nicholas J Wareham; Nabila Bouatia-Naji; Mark I McCarthy; Paul W Franks; James B Meigs; Tanya M Teslovich; Jose C Florez; Claudia Langenberg; Erik Ingelsson; Inga Prokopenko; Inês Barroso Journal: Nat Genet Date: 2012-08-12 Impact factor: 38.330