OBJECTIVE: Fibroblast growth factor (FGF)-21 is highly expressed in the liver and regulates glucose and lipid metabolism in rodents. The effects of obesity and fatty liver on circulating FGF-21 levels have been described mainly in adults. Herein, we measured plasma FGF-21 levels in lean and obese adolescents with low and high hepatic fat content (HFF% <5.5% and HFF% ≥ 5.5%, respectively) and explored their relationship with hepatic fat content, measures of hepatic apoptosis, and insulin sensitivity. METHODS: A total of 217 lean and obese adolescents with both low and high HFF% (lean = 31; obese low HFF% = 107; and obese high HFF% = 79) underwent an oral glucose tolerance test, a fast gradient magnetic resonance imaging to measure the %HFF and abdominal fat distribution. Cytokeratin 18 levels were measured as a biomarker of liver apoptosis. A subset of adolescents underwent a 2-step hyperinsulinemic-euglycemic clamp, and a liver biopsy (N = 14), to assess insulin sensitivity and steatohepatitis, respectively. RESULTS: Compared to controls, FGF-21 levels were higher in obese youth, especially in those with high HFF (P < .001). FGF-21 significantly correlated with adiposity indexes (P < .001), visceral fat (r² = 0.240, P < .001), hepatic fat content (r² = 0.278, P < .001), cytokeratin 18 (r² = 0.217, P < .001), and alanine aminotransferase (r² = .164, P < .001). In subjects with steatoheaptitis, FGF-21 levels significantly correlated with the nonalcoholic fatty liver disease activity score (r² = 0.27, P = .04). Stepwise regression analysis indicated that these relationships are independent of body mass index, visceral fat, and insulin sensitivity. An inverse correlation was documented with insulin, hepatic resistance indexes, and adipose resistance indexes, which disappeared after adjusting for hepatic fat content. CONCLUSIONS: Plasma FGF-21 levels are increased in obese adolescents, particularly in those with fatty liver. FGF-21 concentrations significantly and independently correlate with hepatic fat content and markers of hepatic apoptosis in obese youths.
OBJECTIVE:Fibroblast growth factor (FGF)-21 is highly expressed in the liver and regulates glucose and lipid metabolism in rodents. The effects of obesity and fatty liver on circulating FGF-21 levels have been described mainly in adults. Herein, we measured plasma FGF-21 levels in lean and obese adolescents with low and high hepatic fat content (HFF% <5.5% and HFF% ≥ 5.5%, respectively) and explored their relationship with hepatic fat content, measures of hepatic apoptosis, and insulin sensitivity. METHODS: A total of 217 lean and obese adolescents with both low and high HFF% (lean = 31; obese low HFF% = 107; and obese high HFF% = 79) underwent an oral glucose tolerance test, a fast gradient magnetic resonance imaging to measure the %HFF and abdominal fat distribution. Cytokeratin 18 levels were measured as a biomarker of liver apoptosis. A subset of adolescents underwent a 2-step hyperinsulinemic-euglycemic clamp, and a liver biopsy (N = 14), to assess insulin sensitivity and steatohepatitis, respectively. RESULTS: Compared to controls, FGF-21 levels were higher in obese youth, especially in those with high HFF (P < .001). FGF-21 significantly correlated with adiposity indexes (P < .001), visceral fat (r² = 0.240, P < .001), hepatic fat content (r² = 0.278, P < .001), cytokeratin 18 (r² = 0.217, P < .001), and alanine aminotransferase (r² = .164, P < .001). In subjects with steatoheaptitis, FGF-21 levels significantly correlated with the nonalcoholic fatty liver disease activity score (r² = 0.27, P = .04). Stepwise regression analysis indicated that these relationships are independent of body mass index, visceral fat, and insulin sensitivity. An inverse correlation was documented with insulin, hepatic resistance indexes, and adipose resistance indexes, which disappeared after adjusting for hepatic fat content. CONCLUSIONS: Plasma FGF-21 levels are increased in obese adolescents, particularly in those with fatty liver. FGF-21 concentrations significantly and independently correlate with hepatic fat content and markers of hepatic apoptosis in obese youths.
Authors: Catherine W Yeckel; Sara E Taksali; James Dziura; Ram Weiss; Tania S Burgert; Robert S Sherwin; William V Tamborlane; Sonia Caprio Journal: J Clin Endocrinol Metab Date: 2004-11-02 Impact factor: 5.958
Authors: Tania S Burgert; Sara E Taksali; James Dziura; T Robin Goodman; Catherine W Yeckel; Xenophon Papademetris; R Todd Constable; Ram Weiss; William V Tamborlane; Mary Savoye; Aisha A Seyal; Sonia Caprio Journal: J Clin Endocrinol Metab Date: 2006-08-15 Impact factor: 5.958
Authors: Alexei Kharitonenkov; Tatiyana L Shiyanova; Anja Koester; Amy M Ford; Radmila Micanovic; Elizabeth J Galbreath; George E Sandusky; Lisa J Hammond; Julie S Moyers; Rebecca A Owens; Jesper Gromada; Joseph T Brozinick; Eric D Hawkins; Victor J Wroblewski; De-Shan Li; Farrokh Mehrbod; S Richard Jaskunas; Armen B Shanafelt Journal: J Clin Invest Date: 2005-05-02 Impact factor: 14.808
Authors: David E Kleiner; Elizabeth M Brunt; Mark Van Natta; Cynthia Behling; Melissa J Contos; Oscar W Cummings; Linda D Ferrell; Yao-Chang Liu; Michael S Torbenson; Aynur Unalp-Arida; Matthew Yeh; Arthur J McCullough; Arun J Sanyal Journal: Hepatology Date: 2005-06 Impact factor: 17.425
Authors: Ram Weiss; Sylvie Dufour; Sara E Taksali; William V Tamborlane; Kitt F Petersen; Riccardo C Bonadonna; Linda Boselli; Gina Barbetta; Karin Allen; Francis Rife; Mary Savoye; James Dziura; Robert Sherwin; Gerald I Shulman; Sonia Caprio Journal: Lancet Date: 2003-09-20 Impact factor: 79.321
Authors: Yasushi Ogawa; Hiroshi Kurosu; Masaya Yamamoto; Animesh Nandi; Kevin P Rosenblatt; Regina Goetz; Anna V Eliseenkova; Moosa Mohammadi; Makoto Kuro-o Journal: Proc Natl Acad Sci U S A Date: 2007-04-23 Impact factor: 11.205
Authors: Laurie R Braun; Meghan N Feldpausch; Natalia Czerwonka; Martin Torriani; Steven K Grinspoon; Takara L Stanley Journal: Growth Horm IGF Res Date: 2017-10-07 Impact factor: 2.372
Authors: Lucia Pacifico; Claudio Chiesa; Caterina Anania; Antonio De Merulis; John Frederick Osborn; Sara Romaggioli; Eugenio Gaudio Journal: World J Gastroenterol Date: 2014-07-21 Impact factor: 5.742
Authors: A Esteghamati; A Khandan; A Momeni; A Behdadnia; A Ghajar; M S Nikdad; S Noshad; M Nakhjavani; M Afarideh Journal: Ir J Med Sci Date: 2017-02-08 Impact factor: 1.568