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

Weiqin Chen, Benny Chang, Lan Li, Lawrence Chan

Research output: Contribution to journalArticle

134 Citations (Scopus)

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 Lepob/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 Lepob/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.

Original languageEnglish (US)
Pages (from-to)1134-1142
Number of pages9
JournalHepatology
Volume52
Issue number3
DOIs
StatePublished - Sep 1 2010

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Phospholipases
Fatty Liver
Liver Diseases
Liver
Messenger RNA
Diet
Insulin Resistance
Alcoholic Fatty Liver
Alcoholic Liver Diseases
Gene Targeting
adiponutrin
High Fat Diet
Enzymes
Aspartate Aminotransferases
Body Composition
Lipase
Alanine Transaminase
Sucrose
Triglycerides
Obesity

ASJC Scopus subject areas

  • Hepatology

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Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease. / Chen, Weiqin; Chang, Benny; Li, Lan; Chan, Lawrence.

In: Hepatology, Vol. 52, No. 3, 01.09.2010, p. 1134-1142.

Research output: Contribution to journalArticle

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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 Lepob/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 Lepob/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.",
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AB - 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 Lepob/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 Lepob/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.

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