A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans
(2009) In Diabetologia 52(6). p.1056-1060- Abstract
- It has recently been suggested that the rs738409 G allele in PNPLA3, which encodes adiponutrin, is strongly associated with increased liver fat content in three different ethnic groups. The aims of the present study were as follows: (1) to try to replicate these findings in European individuals with quantitative measures of hepatic fat content; (2) to study whether the polymorphism influences hepatic and adipose tissue insulin sensitivity; and (3) to investigate whether PNPLA3 expression is altered in the human fatty liver. We genotyped 291 Finnish individuals in whom liver fat had been measured using proton magnetic resonance spectroscopy. Hepatic PNPLA3 expression was measured in 32 participants. Hepatic and adipose tissue insulin... (More)
- It has recently been suggested that the rs738409 G allele in PNPLA3, which encodes adiponutrin, is strongly associated with increased liver fat content in three different ethnic groups. The aims of the present study were as follows: (1) to try to replicate these findings in European individuals with quantitative measures of hepatic fat content; (2) to study whether the polymorphism influences hepatic and adipose tissue insulin sensitivity; and (3) to investigate whether PNPLA3 expression is altered in the human fatty liver. We genotyped 291 Finnish individuals in whom liver fat had been measured using proton magnetic resonance spectroscopy. Hepatic PNPLA3 expression was measured in 32 participants. Hepatic and adipose tissue insulin sensitivities were measured using a euglycaemic-hyperinsulinaemic (insulin infusion 0.3 mU kg(-1) min(-1)) clamp technique combined with infusion of [3-H-3]glucose in 109 participants. The rs738409 G allele in PNPLA3 was associated with increased quantitative measures of liver fat content (p = 0.011) and serum aspartate aminotransferase concentrations (p = 0.002) independently of age, sex and BMI. Fasting serum insulin and hepatic and adipose tissue insulin sensitivity were related to liver fat content independently of genotype status. PNPLA3 mRNA expression in the liver was positively related to obesity (r = 0.62, p < 0.0001) and to liver fat content (r = 0.58, p = 0.025) in participants who were not morbidly obese (BMI < 40 kg/m(2)). A common variant in PNPLA3 increases the risk of hepatic steatosis in humans. (Less)
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https://lup.lub.lu.se/record/1428003
- author
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Non-alcoholic fatty liver, disease, rs738409, Liver enzymes, Hepatic insulin sensitivity, Gene expression, Adiponutrin, Adipose tissue insulin sensitivity
- in
- Diabetologia
- volume
- 52
- issue
- 6
- pages
- 1056 - 1060
- publisher
- Springer
- external identifiers
-
- wos:000265684500011
- scopus:67349174005
- ISSN
- 1432-0428
- DOI
- 10.1007/s00125-009-1285-z
- language
- English
- LU publication?
- yes
- id
- 89577a1d-9226-457b-adfd-e3110bd57d0a (old id 1428003)
- date added to LUP
- 2016-04-01 12:35:27
- date last changed
- 2024-04-09 18:31:30
@article{89577a1d-9226-457b-adfd-e3110bd57d0a, abstract = {{It has recently been suggested that the rs738409 G allele in PNPLA3, which encodes adiponutrin, is strongly associated with increased liver fat content in three different ethnic groups. The aims of the present study were as follows: (1) to try to replicate these findings in European individuals with quantitative measures of hepatic fat content; (2) to study whether the polymorphism influences hepatic and adipose tissue insulin sensitivity; and (3) to investigate whether PNPLA3 expression is altered in the human fatty liver. We genotyped 291 Finnish individuals in whom liver fat had been measured using proton magnetic resonance spectroscopy. Hepatic PNPLA3 expression was measured in 32 participants. Hepatic and adipose tissue insulin sensitivities were measured using a euglycaemic-hyperinsulinaemic (insulin infusion 0.3 mU kg(-1) min(-1)) clamp technique combined with infusion of [3-H-3]glucose in 109 participants. The rs738409 G allele in PNPLA3 was associated with increased quantitative measures of liver fat content (p = 0.011) and serum aspartate aminotransferase concentrations (p = 0.002) independently of age, sex and BMI. Fasting serum insulin and hepatic and adipose tissue insulin sensitivity were related to liver fat content independently of genotype status. PNPLA3 mRNA expression in the liver was positively related to obesity (r = 0.62, p < 0.0001) and to liver fat content (r = 0.58, p = 0.025) in participants who were not morbidly obese (BMI < 40 kg/m(2)). A common variant in PNPLA3 increases the risk of hepatic steatosis in humans.}}, author = {{Kotronen, A. and Johansson, L. E. and Johansson, L. M. and Roos, C. and Westerbacka, J. and Hamsten, A. and Bergholm, R. and Arkkila, P. and Arola, J. and Kiviluoto, T. and Fisher, R. M. and Ehrenborg, E. and Orho-Melander, Marju and Ridderstråle, Martin and Groop, Leif and Yki-Jarvinen, H.}}, issn = {{1432-0428}}, keywords = {{Non-alcoholic fatty liver; disease; rs738409; Liver enzymes; Hepatic insulin sensitivity; Gene expression; Adiponutrin; Adipose tissue insulin sensitivity}}, language = {{eng}}, number = {{6}}, pages = {{1056--1060}}, publisher = {{Springer}}, series = {{Diabetologia}}, title = {{A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans}}, url = {{http://dx.doi.org/10.1007/s00125-009-1285-z}}, doi = {{10.1007/s00125-009-1285-z}}, volume = {{52}}, year = {{2009}}, }