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Hepatic MGAT1 is directly regulated by PPARγ2 and promotes fatty liver
Author(s) -
lee yoojeong,
Kim Jae-woo
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.570.3
Subject(s) - steatosis , medicine , downregulation and upregulation , endocrinology , chemistry , peroxisome proliferator activated receptor , biology , biochemistry , gene
There are two biochemical patheways for triacylglycerol (TG) synthesis, the glycerol 3‐phosphate pathway and the MGAT pathway. MGAT pathway is merely involved in the TG biosynthesis because of the very low expression and activity of MGAT1 in normal liver. However, MGAT1 expression increased robustly in liver of ob/ob mice. We found that MGAT1 is upregulated in high fat fed B6 mice but not in C3H mice, which do not express PPARγ in liver. This indicates that MGAT1 is one of the target genes regulated by PPARγ. Moreover, the experiment using adenoviral‐PPARγ2 showed that MGAT1 mRNA level was increased by PPARγ2. Overexpression of MGAT1 dramatically increased the lipid droplets, suggesting that MGAT1 is responsible for the increased TG synthesis. Moreover, B6 mice injected with adenoviral‐MGAT1 resulted in significantly increased TG level in liver. These findings suggest that enhanced TG synthesis may be due to activated MGAT1 pathway by overexpression of MGAT1, indirectly glycerol 3‐phosphate pathway. Taken together, we concluded that PPARγ upregulates MGAT1 expression, thereby promoting alternative pathway of TG synthesis, which resulted in the hepatic steatosis. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011‐0030711 and 2011‐0015665).