Pnpla3I148M knockin mice accumulate PNPLA3 on lipid droplets and develop hepatic steatosis.

ABSTRACT:

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A sequence polymorphism (rs738409, I148M) in patatin-like phospholipid domain containing protein 3 (PNPLA3) is strongly associated with nonalcoholic fatty liver disease (NAFLD), but the mechanistic basis for this association remains enigmatic. Neither ablation nor overexpression of wild-type PNPLA3 affects liver fat content in mice, whereas hepatic overexpression of the human 148M transgene causes steatosis. To determine whether the 148M allele causes fat accumulation in the liver when expressed at physiological levels, we introduced a methionine codon at position 148 of the mouse Pnpla3 gene. Knockin mice had normal levels of hepatic fat on a chow diet, but when challenged with a high-sucrose diet their liver fat levels increased 2 to 3-fold compared to wild-type litter

SUBMITTER: Smagris E 

PROVIDER: S-EPMC4262735 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature