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


CONCLUSIONS
Loss of Pnpla3 does not cause fatty liver, liver enzyme elevation, or insulin resistance in mice.
Chen
Weiqin
W
Diabetes and Endocrinology Research Center, Section of Diabetes and Endocrinology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Chang
Benny
B
Li
Lan
L
Chan
Lawrence
L
D000273:Adipose Tissue / Q000378:metabolism*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001823:Body Composition; D001835:Body Weight; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism*; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D054512:Phospholipases A2, Calcium-Independent / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism; D000217:Acyltransferases
D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D054512:Phospholipases A2, Calcium-Independent; D014280:Triglycerides; C549791:PNPLA3 protein, mouse; D000217:Acyltransferases