title: Circulating triacylglycerol signatures in nonalcoholic fatty liver disease associated with the I148M variant in PNPLA3 and with obesity.
abstract: We examined whether relative concentrations of circulating triacylglycerols (TAGs) between carriers compared with noncarriers of PNPLA3(I148M) gene variant display deficiency of TAGs, which accumulate in the liver because of defective lipase activity. We also analyzed the effects of obesity-associated nonalcoholic fatty liver disease (NAFLD) independent of genotype, and of NAFLD due to either PNPLA3(I148M) gene variant or obesity on circulating TAGs. A total of 372 subjects were divided into groups based on PNPLA3 genotype or obesity. Absolute and relative deficiency of distinct circulating TAGs was observed in the PNPLA3(148MM/148MI) compared with the PNPLA3(148II) group. Obese and 'nonobese' groups had similar PNPLA3 genotypes, but the obese subjects were insulin-resistant. Liver fat was similarly increased in obese and PNPLA3(148MM/148MI) groups. Relative concentrations of TAGs in the obese subjects versus nonobese displayed multiple changes. These closely resembled those between obese subjects with NAFLD but without PNPLA3(I148M) versus those with the I148M variant and NAFLD. The etiology of NAFLD influences circulating TAG profiles. 'PNPLA3 NAFLD' is associated with a relative deficiency of TAGs, supporting the idea that the I148M variant impedes intrahepatocellular lipolysis rather than stimulates TAG synthesis. 'Obese NAFLD' is associated with multiple changes in TAGs, which can be attributed to obesity/insulin resistance rather than increased liver fat content per se.
authors.affiliation: Department of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Jenni
authors.initials: J
authors.lastname: Hyysalo
authors.forename: Peddinti
authors.initials: P
authors.lastname: Gopalacharyulu
authors.forename: Hua
authors.initials: H
authors.lastname: Bian
authors.forename: Tuulia
authors.initials: T
authors.lastname: Hyötyläinen
authors.forename: Marja
authors.initials: M
authors.lastname: Leivonen
authors.forename: Nabil
authors.initials: N
authors.lastname: Jaser
authors.forename: Anne
authors.initials: A
authors.lastname: Juuti
authors.forename: Miikka-Juhani
authors.initials: MJ
authors.lastname: Honka
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.forename: Vesa M
authors.initials: VM
authors.lastname: Olkkonen
authors.forename: Matej
authors.initials: M
authors.lastname: Oresic
authors.forename: Hannele
authors.initials: H
authors.lastname: Yki-Järvinen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005234:Fatty Liver / Q000097:blood* / Q000150:complications / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000150:complications / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood*; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D008049:Lipase; D008565:Membrane Proteins; D014280:Triglycerides; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent