Circulating Triacylglycerol Signatures in Nonalcoholic Fatty Liver Disease Associated With the I148M Variant in PNPLA3 and With Obesity
- Jenni Hyysalo1,2⇑,
- Peddinti Gopalacharyulu3,
- Hua Bian2,
- Tuulia Hyötyläinen3,
- Marja Leivonen4,
- Nabil Jaser4,
- Anne Juuti4,
- Miikka-Juhani Honka5,
- Pirjo Nuutila5,
- Vesa M. Olkkonen2,
- Matej Oresic3 and
- Hannele Yki-Järvinen1,2
- 1Department of Medicine, University of Helsinki, Helsinki, Finland
- 2Minerva Foundation Institute for Medical Research, Helsinki, Finland
- 3VTT Technical Research Centre of Finland, Espoo, Finland
- 4Department of Surgery, Helsinki University Central Hospital, Vantaa, Finland
- 5Turku PET Centre, University of Turku, Turku, Finland
- Corresponding author: Jenni Hyysalo, .
We examined whether relative concentrations of circulating triacylglycerols (TAGs) between carriers compared with noncarriers of PNPLA3I148M 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 PNPLA3I148M 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 PNPLA3148MM/148MI compared with the PNPLA3148II group. Obese and ‘nonobese’ groups had similar PNPLA3 genotypes, but the obese subjects were insulin-resistant. Liver fat was similarly increased in obese and PNPLA3148MM/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 PNPLA3I148M 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.
See accompanying commentary, p. 42.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-0774/-/DC1.
- Received May 15, 2013.
- Accepted August 23, 2013.
- © 2014 by the American Diabetes Association.
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