Mohammad S Siddiqui1, Michael Fuchs2, Michael O Idowu3, Velimir A Luketic2, Sherry Boyett2, Carol Sargeant2, Richard T Stravitz2, Puneet Puri2, Scott Matherly2, Richard K Sterling2, Melissa Contos3, Arun J Sanyal2. 1. Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia. Electronic address: mssiddiqui@mcvh-vcu.edu. 2. Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia. 3. Division of Surgical Pathology, Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
Abstract
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated independently with increased cardiovascular mortality. Although NAFLD is associated with dyslipidemia, it is not clear whether recently identified markers of cardiovascular risk indicate liver disease progression in patients with histologically confirmed NAFLD. We evaluated an extensive panel of serum markers of cardiovascular risk in nondiabetic patients with histologically proven NAFLD. METHODS: We performed a case-control study in which we compared serum levels of laboratory markers of cardiovascular risk among 81 nondiabetic subjects with histologically confirmed NAFLD vs lean (N = 81) and obese (N = 81) individuals without NAFLD (based on liver fat score, controls). For ex vivo studies, liver tissues were obtained from subjects undergoing elective cholecystectomy or from a tissue repository. RESULTS: Subjects with NAFLD had increased serum levels of insulin, triglycerides, and apolipoprotein B; increased size and concentration of very large density lipoprotein particles; increased concentrations of low-density lipoprotein (LDL) particles and small dense LDL (sdLDL) cholesterol, and an increased percentage of sdLDL, compared with controls. Although nonalcoholic steatohepatitis was associated with a worse profile of serum atherogenic markers than NAFLD, these differences did not reach statistical significance. Despite hyperinsulinemia, triglyceride and apolipoprotein B levels, concentrations of LDL particles and LDL cholesterol, and sdLDL-related parameters decreased significantly in patients with cirrhosis. Ex vivo studies showed that patients with NAFLD had increased sensitivity of hepatic triglyceride levels and cholesterol synthesis to insulin, and that sensitivity increased the development of cirrhosis. CONCLUSIONS: Atherogenic dyslipidemia is related to increased insulin-induced hepatic lipid synthesis in patients with NAFLD. Reduced dyslipidemia in patients with cirrhosis is associated with increased insulin resistance and possibly failed lipid synthesis.
BACKGROUND & AIMS:Nonalcoholic fatty liver disease (NAFLD) is associated independently with increased cardiovascular mortality. Although NAFLD is associated with dyslipidemia, it is not clear whether recently identified markers of cardiovascular risk indicate liver disease progression in patients with histologically confirmed NAFLD. We evaluated an extensive panel of serum markers of cardiovascular risk in nondiabeticpatients with histologically proven NAFLD. METHODS: We performed a case-control study in which we compared serum levels of laboratory markers of cardiovascular risk among 81 nondiabetic subjects with histologically confirmed NAFLD vs lean (N = 81) and obese (N = 81) individuals without NAFLD (based on liver fat score, controls). For ex vivo studies, liver tissues were obtained from subjects undergoing elective cholecystectomy or from a tissue repository. RESULTS: Subjects with NAFLD had increased serum levels of insulin, triglycerides, and apolipoprotein B; increased size and concentration of very large density lipoprotein particles; increased concentrations of low-density lipoprotein (LDL) particles and small dense LDL (sdLDL) cholesterol, and an increased percentage of sdLDL, compared with controls. Although nonalcoholic steatohepatitis was associated with a worse profile of serum atherogenic markers than NAFLD, these differences did not reach statistical significance. Despite hyperinsulinemia, triglyceride and apolipoprotein B levels, concentrations of LDL particles and LDL cholesterol, and sdLDL-related parameters decreased significantly in patients with cirrhosis. Ex vivo studies showed that patients with NAFLD had increased sensitivity of hepatic triglyceride levels and cholesterol synthesis to insulin, and that sensitivity increased the development of cirrhosis. CONCLUSIONS: Atherogenic dyslipidemia is related to increased insulin-induced hepatic lipid synthesis in patients with NAFLD. Reduced dyslipidemia in patients with cirrhosis is associated with increased insulin resistance and possibly failed lipid synthesis.
Authors: Andrew Paul DeFilippis; Michael J Blaha; Seth S Martin; Robert M Reed; Steven R Jones; Khurram Nasir; Roger S Blumenthal; Matthew J Budoff Journal: Atherosclerosis Date: 2013-01-29 Impact factor: 5.162
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: Piia Simonen; Anna Kotronen; Maarit Hallikainen; Ksenia Sevastianova; Janne Makkonen; Antti Hakkarainen; Nina Lundbom; Tatu A Miettinen; Helena Gylling; Hannele Yki-Järvinen Journal: J Hepatol Date: 2010-08-22 Impact factor: 25.083
Authors: Anna M G Cali; Tosca L Zern; Sara E Taksali; Ana Mayra de Oliveira; Sylvie Dufour; James D Otvos; Sonia Caprio Journal: Diabetes Care Date: 2007-08-23 Impact factor: 19.112
Authors: Elisa Fabbrini; Faidon Magkos; B Selma Mohammed; Terri Pietka; Nada A Abumrad; Bruce W Patterson; Adewole Okunade; Samuel Klein Journal: Proc Natl Acad Sci U S A Date: 2009-08-24 Impact factor: 11.205
Authors: William C Cromwell; James D Otvos; Michelle J Keyes; Michael J Pencina; Lisa Sullivan; Ramachandran S Vasan; Peter W F Wilson; Ralph B D'Agostino Journal: J Clin Lipidol Date: 2007-12 Impact factor: 4.766
Authors: M Adiels; M-R Taskinen; C Packard; M J Caslake; A Soro-Paavonen; J Westerbacka; S Vehkavaara; A Häkkinen; S-O Olofsson; H Yki-Järvinen; J Borén Journal: Diabetologia Date: 2006-02-04 Impact factor: 10.122
Authors: Ling Li; Gurkan Bebek; Stephen F Previs; Jonathan D Smith; Rovshan G Sadygov; Arthur J McCullough; Belinda Willard; Takhar Kasumov Journal: J Proteome Res Date: 2016-08-05 Impact factor: 4.466
Authors: Justin McNair Canada; Antonio Abbate; Rebecca Collen; Hayley Billingsley; Leo Francis Buckley; Salvatore Carbone; Cory Ross Trankle; Michael Ola Idowu; Dinesh Kadariya; Benjamin Van Tassell; Arun Jayant Sanyal; Mohammad Shadab Siddiqui Journal: Am J Cardiol Date: 2018-11-06 Impact factor: 2.778
Authors: Zehra Esra Ilhan; John K DiBaise; Nancy G Isern; David W Hoyt; Andrew K Marcus; Dae-Wook Kang; Michael D Crowell; Bruce E Rittmann; Rosa Krajmalnik-Brown Journal: ISME J Date: 2017-05-26 Impact factor: 10.302
Authors: Kathleen E Corey; Laura A Wilson; Akif Altinbas; Katherine P Yates; David E Kleiner; Raymond T Chung; Ronald M Krauss; Naga Chalasani Journal: Aliment Pharmacol Ther Date: 2019-03-10 Impact factor: 8.171
Authors: Zhenghui G Jiang; Elliot B Tapper; Misung Kim; Margery A Connelly; Sarah A Krawczyk; Eric U Yee; Mark A Herman; Kenneth J Mukamal; Michelle Lai Journal: J Clin Gastroenterol Date: 2018 May/Jun Impact factor: 3.062
Authors: Mohammad Shadab Siddiqui; Mark L Van Natta; Margery A Connelly; Raj Vuppalanchi; Brent A Neuschwander-Tetri; James Tonascia; Cynthia Guy; Rohit Loomba; Srinivasan Dasarathy; Julia Wattacheril; Naga Chalasani; Arun J Sanyal Journal: J Hepatol Date: 2019-10-18 Impact factor: 25.083