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Hepatology. 2010 Sep;52(3):1134-42. doi: 10.1002/hep.23812.

Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease.

Author information

  • 1Diabetes and Endocrinology Research Center, Section of Diabetes and Endocrinology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.

Erratum in

  • Hepatology. 2010 Dec;52(6):2250.

Abstract

PNPLA3 (adiponutrin), a novel patatin-like phospholipase domain-containing enzyme, is expressed at high level in fat, but also in other tissues including liver. Polymorphisms in PNPLA3 have been linked to obesity and insulin sensitivity. Notably, a nonsynonymous variant rs738409(G) allele of the PNPLA3 gene was found to be strongly associated with both nonalcoholic and alcoholic fatty liver disease. We have generated Pnpla3(-/-) mice by gene targeting. Loss of Pnpla3 has no effect on body weight or composition, adipose mass, or development, whether the mice were fed regular chow or high-fat diet or bred into the genetic obese Lep(ob/ob) background. Plasma and liver triglyceride content and plasma aspartate aminotransferase and alanine aminotransferase levels were not different between Pnpla3(+/+) and Pnpla3(-/-) mice while they were on regular chow, fed three different fatty liver-inducing diets, or after they were bred into Lep(ob/ob) background. Hepatic Pnpla5 messenger RNA (mRNA) levels were similar in wild-type and Pnpla3(-/-) mice, although adipose Pnpla5 mRNA level was increased in Pnpla3(-/-) mice. A high-sucrose lipogenic diet stimulated hepatic Pnpla3 and Pnpla5 mRNA levels to a similar degree, but it did not affect adipose or liver triglyceride lipase (ATGL, known also as Pnpla2) mRNA in Pnpla3(+/+) and Pnpla3(-/-) mice. Finally, Pnpla3(+/+) and Pnpla3(-/-) mice displayed similar glucose tolerance and insulin tolerance tests while on regular chow or three different fatty liver-inducing diets.

CONCLUSION:

Loss of Pnpla3 does not cause fatty liver, liver enzyme elevation, or insulin resistance in mice.

Comment in

PMID:
20648554
[PubMed - indexed for MEDLINE]
PMCID:
PMC2932863
Free PMC Article

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