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Review
. 2016 Apr 27;17(5):633.
doi: 10.3390/ijms17050633.

Definitions of Normal Liver Fat and the Association of Insulin Sensitivity with Acquired and Genetic NAFLD-A Systematic Review

Elina M Petäjä  1   2 , Hannele Yki-Järvinen  3   4
Affiliations
Review

Definitions of Normal Liver Fat and the Association of Insulin Sensitivity with Acquired and Genetic NAFLD-A Systematic Review

Elina M Petäjä et al. Int J Mol Sci. .

Abstract

Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of disease ranging from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) and fibrosis. "Obese/Metabolic NAFLD" is closely associated with obesity and insulin resistance and therefore predisposes to type 2 diabetes and cardiovascular disease. NAFLD can also be caused by common genetic variants, the patatin-like phospholipase domain-containing 3 (PNPLA3) or the transmembrane 6 superfamily member 2 (TM6SF2). Since NAFL, irrespective of its cause, can progress to NASH and liver fibrosis, its definition is of interest. We reviewed the literature to identify data on definition of normal liver fat using liver histology and different imaging tools, and analyzed whether NAFLD caused by the gene variants is associated with insulin resistance. Histologically, normal liver fat content in liver biopsies is most commonly defined as macroscopic steatosis in less than 5% of hepatocytes. In the population-based Dallas Heart Study, the upper 95th percentile of liver fat measured by proton magnetic spectroscopy (¹H-MRS) in healthy subjects was 5.6%, which corresponds to approximately 15% histological liver fat. When measured by magnetic resonance imaging (MRI)-based techniques such as the proton density fat fraction (PDFF), 5% macroscopic steatosis corresponds to a PDFF of 6% to 6.4%. In contrast to "Obese/metabolic NAFLD", NAFLD caused by genetic variants is not associated with insulin resistance. This implies that NAFLD is heterogeneous and that "Obese/Metabolic NAFLD" but not NAFLD due to the PNPLA3 or TM6SF2 genetic variants predisposes to type 2 diabetes and cardiovascular disease.

Keywords: PNPLA3; TM6SF2; insulin resistance; liver fat; obesity.

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Figures

Figure 1
Figure 1
Schematic representation of causes and consequences of “Obese/Metabolic NAFLD” (top) and “TM6SF2 NAFLD” and “PNPLA3 NAFLD” (bottom). Abbreviations: BMI, body mass index; CHD, coronary heart disease; DM, diabetes mellitus; FFA, free fatty acids; fS, fasting serum; HCC, hepatocellular carcinoma; HDL, high density lipoprotein; MCP-1, monocyte chemoattractant protein-1; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatits; LDL, low density lipoprotein; P, plasma; PNPLA3, patatin-like phospholipase domain-containing 3; S, serum; TM6SF2, transmembrane 6 superfamily member 2; TNF-α, tumor necrosis factor-α.
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References

    1. Chalasani N., Younossi Z., Lavine J.E., Diehl A.M., Brunt E.M., Cusi K., Charlton M., Sanyal A.J. The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Am. J. Gastroenterol. 2012;107:811–826. doi: 10.1038/ajg.2012.128. - DOI - PubMed
    1. Neuschwander-Tetri B.A. Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: The central role of nontriglyceride fatty acid metabolites. Hepatology. 2010;52:774–788. doi: 10.1002/hep.23719. - DOI - PubMed
    1. Brunt E.M., Kleiner D.E., Wilson L.A., Belt P., Neuschwander-Tetri B.A. The NAS and the histopathologic diagnosis in NAFLD: Distinct clinicopathologic meanings. Hepatology. 2011;53:810–820. doi: 10.1002/hep.24127. - DOI - PMC - PubMed
    1. Anstee Q.M., Day C.P. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat. Rev. Gastroenterol. Hepatol. 2013;10:330–344. doi: 10.1038/nrgastro.2013.41. - DOI - PubMed
    1. Angulo P., Kleiner D.E., Dam-Larsen S., Adams L.A., Bjornsson E.S., Charatcharoenwitthaya P., Mills P.R., Keach J.C., Lafferty H.D., Stahler A., et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149:389–397. doi: 10.1053/j.gastro.2015.04.043. - DOI - PMC - PubMed

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