Causal relationship of hepatic fat with liver damage and insulin resistance in nonalcoholic fatty liver

Journal of Internal Medicine

Volumn 283, Issue 4, 2018, Pages 356-370

  Dongiovanni, P ^a   Stender, S ^b   Pietrelli, A ^a,c   Mancina, R M ^d   Cespiati, A ^a   Petta, S ^e   Pelusi, S ^a   Pingitore, P ^d   Badiali, S ^a   Maggioni, M ^a   Mannisto, V ^f   Grimaudo, S ^e   Pipitone, R M ^e   Pihlajamaki, J ^f,g   Craxi, A ^e   Taube, M ^g   Carlsson, L M S ^h   Fargion, S ^a,i   Romeo, S ^d,j,k   Kozlitina, J ^l   Valenti, L ^a,i   more..

^a FONDAZIONE IRCCS CA GRANDA OSPEDALE MAGGIORE POLICLINICO   (Italy)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^c Istituto Nazionale di Genetica Molecolare   (Italy)

^d UNIVERSITY OF GOTHENBURG   (Sweden)

^e UNIVERSITY OF PALERMO   (Italy)

^f KUOPIO UNIVERSITY HOSPITAL   (Finland)

^g UNIVERSITY OF EASTERN FINLAND   (Finland)

^h UNIVERSITY OF GOTHENBURG   (Sweden)

ⁱ UNIVERSITY OF MILAN   (Italy)

^j UNIVERSITY MAGNA GRAECIA OF CATANZARO   (Italy)

^k SAHLGRENSKA UNIVERSITY HOSPITAL   (Sweden)

^l UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

more..

Author keywords

fibrosis; genetics; insulin resistance; mendelian randomization; nonalcoholic fatty liver disease; type 2 diabetes

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; GCKR PROTEIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LIVER ENZYME; LIVER PROTEIN; MBOAT7 PROTEIN; PNPLA3 PROTEIN; TM6SF2 PROTEIN; UNCLASSIFIED DRUG; ACYLTRANSFERASE; ADIPONUTRIN, HUMAN; GCKR PROTEIN, HUMAN; MBOAT7 PROTEIN, HUMAN; MEMBRANE PROTEIN; SIGNAL TRANSDUCING ADAPTOR PROTEIN; TM6SF2 PROTEIN, HUMAN; TRIACYLGLYCEROL LIPASE;

ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALLELE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; COHORT ANALYSIS; DISEASE ACTIVITY; DISEASE SEVERITY; DYSLIPIDEMIA; ETHNICITY; FAT CONTENT; FEMALE; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC RISK; GENETIC VARIATION; HEPATOCELLULAR BALLOONING; HIGH DENSITY LIPOPROTEIN CHOLESTEROL LEVEL; HOMEOSTASIS MODEL ASSESSMENT; HUMAN; HYPERTENSION; INFLAMMATION; INSULIN RESISTANCE; LIPID STORAGE; LIVER BIOPSY; LIVER CIRRHOSIS; LIVER DISEASE; LIVER FIBROSIS; LIVER INJURY; LIVER NECROSIS; MAJOR CLINICAL STUDY; MALE; MENDELIAN RANDOMIZATION ANALYSIS; MIDDLE AGED; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; OBSERVATIONAL STUDY; PLEIOTROPY; PRIORITY JOURNAL; RISK FACTOR; ADIPOSE TISSUE; CHRONIC DISEASE; CLINICAL TRIAL; COMPLICATION; GENETIC MARKER; GENETICS; MULTICENTER STUDY; PHYSIOLOGY; PROSPECTIVE STUDY;

ACYLTRANSFERASES; ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ADIPOSE TISSUE; ADULT; CHRONIC DISEASE; DIABETES MELLITUS, TYPE 2; FEMALE; GENETIC MARKERS; HUMANS; INSULIN RESISTANCE; LIPASE; LIVER CIRRHOSIS; MALE; MEMBRANE PROTEINS; MENDELIAN RANDOMIZATION ANALYSIS; NON-ALCOHOLIC FATTY LIVER DISEASE; PROSPECTIVE STUDIES;

EID: 85042743861     PISSN: 09546820     EISSN: 13652796     Source Type: Journal    
DOI: 10.1111/joim.12719     Document Type: Article

References (45)

1. Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 40: 1387–95.
2. Non-alcoholic Fatty Liver Disease Study G, Lonardo A, Bellentani S, et al. Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups. Dig Liver Dis 2015; 47: 997–1006.
3. Valenti L, Bugianesi E, Pajvani U, Targher G. Nonalcoholic fatty liver disease: cause or consequence of type 2 diabetes? Liver Int 2016; 36: 1563–79.
4. Dyson J, Jaques B, Chattopadyhay D, et al. Hepatocellular cancer: The impact of obesity, type 2 diabetes and a multidisciplinary team. J Hepatol 2014; 60: 110–7.
5. Charlton MR, Burns JM, Pedersen RA, Watt KD, Heimbach JK, Dierkhising RA. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology 2011; 141: 1249–53.
6. van der Poorten D, Samer CF, Ramezani-Moghadam M, et al. Hepatic fat loss in advanced nonalcoholic steatohepatitis: are alterations in serum adiponectin the cause? Hepatology 2013; 57: 2180–8.
7. Bril F, Barb D, Portillo-Sanchez P, et al. Metabolic and histological implications of intrahepatic triglyceride content in nonalcoholic fatty liver disease. Hepatology 2017; 65: 1132–44.
8. Romero-Gomez M, Zelber-Sagi S, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol 2017; 67: 829–46.
9. Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med 2008; 27: 1133–63.
10. Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet 2014; 23: R89–98.
11. Holmes MV, Ala-Korpela M, Smith GD. Mendelian randomization in cardiometabolic disease: challenges in evaluating causality. Nat Rev Cardiol 2017; 14: 577–90.
12. Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008; 40: 1461–5.
13. Speliotes EK, Yerges-Armstrong LM, Wu J, et al. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet 2011; 7: e1001324.
14. Kozlitina J, Smagris E, Stender S, et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2014; 46: 352–6.
15. Holmen OL, Zhang H, Fan Y, et al. Systematic evaluation of coding variation identifies a candidate causal variant in TM6SF2 influencing total cholesterol and myocardial infarction risk. Nat Genet 2014; 46: 345–51.
16. Buch S, Stickel F, Trepo E, et al. A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis. Nat Genet 2015; 47: 1443–8.
17. Mancina RM, Dongiovanni P, Petta S, et al. The MBOAT7-TMC4 Variant rs641738 Increases Risk of Nonalcoholic Fatty Liver Disease in Individuals of European Descent. Gastroenterology 2016; 150: 1219–30. e6
18. Dongiovanni P, Romeo S, Valenti L. Genetic factors in the pathogenesis of nonalcoholic fatty liver and steatohepatitis. Biomed Res Int 2015; 2015: 460190.
19. Yki-Jarvinen H. Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome. Lancet Diabetes Endocrinol 2014; 2: 901–10.
20. Kim DS, Jackson AU, Li YK, et al. Novel association of TM6SF2 rs58542926 genotype with increased serum tyrosine levels and decreased apolipoprotein B-100 particles in Finns. J Lipid Res 2017; 58: 1471–81.
21. Dongiovanni P, Petta S, Maglio C, et al. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology 2015; 61: 506–14.
22. Carlsson LM, Peltonen M, Ahlin S, et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med 2012; 367: 695–704.
23. Victor RG, Haley RW, Willett DL, et al. The Dallas Heart Study: a population-based probability sample for the multidisciplinary study of ethnic differences in cardiovascular health. Am J Cardiol 2004; 93: 1473–80.
24. Bonora E, Targher G, Alberiche M, et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 2000; 23: 57–63.
25. Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41: 1313–21.
26. Petta S, Valenti L, Marra F, et al. MERTK rs4374383 polymorphism affects the severity of fibrosis in non-alcoholic fatty liver disease. J Hepatol 2016; 64: 682–90.
27. Maida M, Macaluso FS, Salomone F, Petta S. Non-invasive assessment of liver injury in non-alcoholic fatty liver disease: a review of literature. Curr Mol Med 2016; 16: 721–37.
28. Kitamoto T, Kitamoto A, Yoneda M, et al. Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan. Hum Genet 2013; 132: 783–92.
29. Manning AK, Hivert MF, Scott RA, et al. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat Genet 2012; 44: 659–69.
30. Fuchsberger C, Flannick J, Teslovich TM, et al. The genetic architecture of type 2 diabetes. Nature 2016; 536: 41–7.
31. Dongiovanni P, Valenti L. Genetics of nonalcoholic fatty liver disease. Metabolism 2016; 65: 1026–37.
32. Burgess S, Thompson SG. Use of allele scores as instrumental variables for Mendelian randomization. Int J Epidemiol 2013; 42: 1134–44.
33. Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology 2015; 149: 389–97: e10.
34. Dongiovanni P, Meroni M, Baselli GA, et al. Insulin resistance promotes Lysyl Oxidase Like 2 induction and fibrosis accumulation in non-alcoholic fatty liver disease. Clin Sci 2017; 131: 1301–15.
35. Yamaguchi K, Yang L, McCall S, et al. Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis. Hepatology 2007; 45: 1366–74.
36. Di Filippo M, Moulin P, Roy P, et al. Homozygous MTTP and APOB mutations may lead to hepatic steatosis and fibrosis despite metabolic differences in congenital hypocholesterolemia. J Hepatol 2014; 61: 891–902.
37. Cui J, Chen CH, Lo MT, et al. Shared genetic effects between hepatic steatosis and fibrosis: A prospective twin study. Hepatology 2016; 64: 1547–58.
38. Mashek DG, Khan SA, Sathyanarayan A, Ploeger JM, Franklin MP. Hepatic lipid droplet biology: Getting to the root of fatty liver. Hepatology 2015; 62: 964–7.
39. Luukkonen PK, Zhou Y, Nidhina Haridas PA, et al. Impaired hepatic lipid synthesis from polyunsaturated fatty acids in TM6SF2 E167K variant carriers with NAFLD. J Hepatol 2017; 67: 128–36.
40. Stender S, Kozlitina J, Nordestgaard BG, Tybjaerg-Hansen A, Hobbs HH, Cohen JC. Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci. Nat Genet 2017; 49: 842–7.
41. Liu DJ, Peloso GM, Yu H, et al. Exome-wide association study of plasma lipids in >300,000 individuals. Nat Genet 2017; 49: 1758–66.
42. Seppala-Lindroos A, Vehkavaara S, Hakkinen AM, et al. Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab 2002; 87: 3023–8.
43. Kumashiro N, Erion DM, Zhang D, et al. Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease. Proc Natl Acad Sci USA 2011; 108: 16381–5.
44. Pirazzi C, Valenti L, Motta BM, et al. PNPLA3 has retinyl-palmitate lipase activity in human hepatic stellate cells. Hum Mol Genet 2014; 23: 4077–85.
45. Boyle EA, Li YI, Pritchard JK. An expanded view of complex traits: from polygenic to omnigenic. Cell 2017; 169: 1177–86.