Advances in Hepatology / 2014 / Article / Tab 1 / Review Article
Targeting Hepatic Glycerolipid Synthesis and Turnover to Treat Fatty Liver Disease Table 1 Effects of modulating expression of triglyceride metabolism enzymes on hepatic steatosis and insulin sensitivity.
Protein Function Normal chow diet High fat diet ob/ob GPAT1 GOF ↑HSv ↓ ISv [36 ] LOF ↓ HSg ↑ISg [37 –39 ]↓ HSg ↑ISg [37 –39 ]↓ HSg ↔ ISg [40 ]GPAT4 LOF ↓ HSg [44 ]↓ HSg [44 ] AGPAT2 LOF ↑HSg [47 ] Lipin 1 GOF ↑HSv [51 ] ↑ISv [56 ]
LOF ↑HSg ↓ ISg [143 , 144 ] LS-LOF ↔ HSg [55 ]↓ HSr ↑ISr [62 ] Lipin 2 GOF ↔ HSv ↔ ISv [66 ]↑HSv ↓ ISv [66 ] LOF ↔ HSr ↔ ISr [66 ] LS-LOF ↓ HSr ↑ISr [66 ] Lipin 3 LOF ↓ HSg [145 ] MOGAT1 LS-LOF ↓ HSg ↑ISr,a [71 , 72 ]↓ HSa ↑ISa [72 ]MOGAT2 LOF ↓ HSg ↑ISg [73 ] DGAT1 LOF ↔ HSg ↑ISg [75 , 76 ]↓ HSg ↑ISg [76 , 77 ]↔ HSa [79 ] ↓ HSg,a [76 ] LS-LOF ↔ HSa [76 ]↔ HSa ↔ ISa [78 ] DGAT2 LOF Lethalg [82 ] LS-LOF ↓ HSa ↑ISa [78 ]↓ HSa ↑ISa rat [78 ] ↓ HSa ↔ ISa mice [83 ] Perilipin 2 (ADRP) GOF LOF ↓ HSg [93 , 94 ]↓ HSg [94 ]↓ HSg ↑ISg [95 ]LS-LOF ↓ HSa ↑ISa [96 , 97 ] Perilipin 5 GOF ↑TGv in cells [98 ] CIDEA LOF ↔ HSg [100 ] ↑ISg ↓ HSg [100 ] ↑ISg [103 ]
↓ HSg [100 ]LS-LOF ↓ HSr [100 ]CIDEB LOF ↔ HSg ↑ISg [104 ]↓ HSg ↑ISg [104 ] CIDEC (Fsp27) GOF ↑TGv in cells [110 ] ↑HSv [110 ] LOF ↓ HSr [110 ]ATGL GOF ↓ HSv [116 , 120 ]LOF ↑HSg,r ↔ ISg,r [114 , 116 , 117 ] LS-LOF ↑HSg [115 ] ↑HSr ↑ISg,r [114 , 117 ] ↑HSg [115 ] HSL GOF ↓ HSv [120 ]LOF ↑HSg [123 ] ↓ HSg [125 , 126 ] ↑HSg [123 ] ↓ HSg [125 , 126 ] ↔ ISg [125 , 126 ]↑ISg [125 ] MAGL LOF ↑ISg [127 ] ↑ISg [127 ] PNPLA3 LS-GOFI148 ↔ HSoe ↔ ISoe [141 ]↔ HSoe [141 ] LS-GOFI148M ↑HSg ↔ ISg [141 ] ↔ HSg [141 ] LOF ↔ HSg ↔ ISg [139 ]↔ HSg ↔ ISg [139 ]
HS: hepatic steatosis; IS: whole-body insulin sensitivity; GOF: gain of function (oe: transgenic overexpression; v: adenoviral overexpression); LOF: loss of function (g: gene knockout; r: RNAi-based disruption; a: ASO); LS-LOF: liver-specific loss of function; LS-GOF: liver-specific gain of function; *UCP-DTA mice used.