Circulating triacylglycerol signatures in nonalcoholic fatty liver disease associated with the I148M variant in PNPLA3 and with obesity

J Hyysalo (Corresponding Author), Peddinti Gopalacharyulu, H Bian, T Hyötyläinen, M Leivonen, N Jaser, A Juuti, M-J Honka, P Nuutila, V M Olkkonen, Matej Oresic, H Yki-Järvinen

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Abstract

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 PNPLA3 148II group. Obese and 'nonobese' groups had similar PNPLA3 genotypes, but the obese subjects were insulinresistant. 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
Original languageEnglish
Pages (from-to)312-322
JournalDiabetes
Volume63
Issue number1
DOIs
Publication statusPublished - 2014
MoE publication typeA1 Journal article-refereed

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Triglycerides
Obesity
Genotype
Liver
Fats
Non-alcoholic Fatty Liver Disease
Lipolysis
Lipase
Genes
Insulin Resistance

Cite this

Hyysalo, J., Gopalacharyulu, P., Bian, H., Hyötyläinen, T., Leivonen, M., Jaser, N., ... Yki-Järvinen, H. (2014). Circulating triacylglycerol signatures in nonalcoholic fatty liver disease associated with the I148M variant in PNPLA3 and with obesity. Diabetes, 63(1), 312-322. https://doi.org/10.2337/db13-0774
Hyysalo, J ; Gopalacharyulu, Peddinti ; Bian, H ; Hyötyläinen, T ; Leivonen, M ; Jaser, N ; Juuti, A ; Honka, M-J ; Nuutila, P ; Olkkonen, V M ; Oresic, Matej ; Yki-Järvinen, H. / Circulating triacylglycerol signatures in nonalcoholic fatty liver disease associated with the I148M variant in PNPLA3 and with obesity. In: Diabetes. 2014 ; Vol. 63, No. 1. pp. 312-322.
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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 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 PNPLA3 148II group. Obese and 'nonobese' groups had similar PNPLA3 genotypes, but the obese subjects were insulinresistant. 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",
author = "J Hyysalo and Peddinti Gopalacharyulu and H Bian and T Hy{\"o}tyl{\"a}inen and M Leivonen and N Jaser and A Juuti and M-J Honka and P Nuutila and Olkkonen, {V M} and Matej Oresic and H Yki-J{\"a}rvinen",
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Hyysalo, J, Gopalacharyulu, P, Bian, H, Hyötyläinen, T, Leivonen, M, Jaser, N, Juuti, A, Honka, M-J, Nuutila, P, Olkkonen, VM, Oresic, M & Yki-Järvinen, H 2014, 'Circulating triacylglycerol signatures in nonalcoholic fatty liver disease associated with the I148M variant in PNPLA3 and with obesity', Diabetes, vol. 63, no. 1, pp. 312-322. https://doi.org/10.2337/db13-0774

Circulating triacylglycerol signatures in nonalcoholic fatty liver disease associated with the I148M variant in PNPLA3 and with obesity. / Hyysalo, J (Corresponding Author); Gopalacharyulu, Peddinti; Bian, H; Hyötyläinen, T; Leivonen, M; Jaser, N; Juuti, A; Honka, M-J; Nuutila, P; Olkkonen, V M; Oresic, Matej; Yki-Järvinen, H.

In: Diabetes, Vol. 63, No. 1, 2014, p. 312-322.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Circulating triacylglycerol signatures in nonalcoholic fatty liver disease associated with the I148M variant in PNPLA3 and with obesity

AU - Hyysalo, J

AU - Gopalacharyulu, Peddinti

AU - Bian, H

AU - Hyötyläinen, T

AU - Leivonen, M

AU - Jaser, N

AU - Juuti, A

AU - Honka, M-J

AU - Nuutila, P

AU - Olkkonen, V M

AU - Oresic, Matej

AU - Yki-Järvinen, H

PY - 2014

Y1 - 2014

N2 - 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 PNPLA3 148II group. Obese and 'nonobese' groups had similar PNPLA3 genotypes, but the obese subjects were insulinresistant. 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

AB - 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 PNPLA3 148II group. Obese and 'nonobese' groups had similar PNPLA3 genotypes, but the obese subjects were insulinresistant. 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

U2 - 10.2337/db13-0774

DO - 10.2337/db13-0774

M3 - Article

VL - 63

SP - 312

EP - 322

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 1

ER -