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	↑HS^v↓IS^v [36]
	LOF	↓HS^g ↑IS^g [37–39]	↓HS^g ↑IS^g [37–39]	↓HS^g↔IS^g [40]
GPAT4	LOF	↓HS^g [44]	↓HS^g [44]
AGPAT2	LOF	↑HS^g [47]
Lipin 1	GOF	↑HS^v [51]		↑IS^v [56]∗
	LOF	↑HS^g↓IS^g [143, 144]
	LS-LOF	↔HS^g [55]	↓HS^r ↑IS^r [62]
Lipin 2	GOF	↔HS^v↔IS^v [66]	↑HS^v↓IS^v [66]
	LOF	↔HS^r↔IS^r [66]
	LS-LOF		↓HS^r ↑IS^r [66]
Lipin 3	LOF	↓HS^g [145]
MOGAT1	LS-LOF		↓HS^g ↑IS^r,a [71, 72]	↓HS^a ↑IS^a [72]
MOGAT2	LOF		↓HS^g ↑IS^g [73]
DGAT1	LOF	↔HS^g ↑IS^g [75, 76]	↓HS^g ↑IS^g [76, 77]	↔HS^a [79]
			↓HS^g,a [76]
	LS-LOF	↔HS^a [76]	↔HS^a↔IS^a [78]
DGAT2	LOF	Lethal^g [82]
	LS-LOF	↓HS^a ↑IS^a [78]	↓HS^a ↑IS^a rat [78]
			↓HS^a↔IS^a mice [83]
Perilipin 2; (ADRP)	GOF
	LOF	↓HS^g [93, 94]	↓HS^g [94]	↓HS^g ↑IS^g [95]
	LS-LOF		↓HS^a ↑IS^a [96, 97]
Perilipin 5	GOF	↑TG^v in cells [98]
CIDEA	LOF	↔HS^g [100] ↑IS^g	↓HS^g [100] ↑IS^g [103]#	↓HS^g [100]
	LS-LOF			↓HS^r [100]
CIDEB	LOF	↔HS^g ↑IS^g [104]	↓HS^g ↑IS^g [104]
CIDEC; (Fsp27)	GOF	↑TG^v in cells [110]		↑HS^v [110]
	LOF			↓HS^r [110]
ATGL	GOF			↓HS^v [116, 120]
	LOF	↑HS^g,r↔IS^g,r [114, 116, 117]
	LS-LOF	↑HS^g [115]	↑HS^r ↑IS^g,r [114, 117]
			↑HS^g [115]
HSL	GOF			↓HS^v [120]
	LOF	↑HS^g [123] ↓HS^g [125, 126]	↑HS^g [123] ↓HS^g [125, 126]
		↔IS^g [125, 126]	↑IS^g [125]
MAGL	LOF	↑IS^g [127]	↑IS^g [127]
PNPLA3	LS-GOF^I148	↔HS^oe↔IS^oe [141]	↔HS^oe [141]
	LS-GOF^I148M	↑HS^g↔IS^g [141]	↔HS^g [141]
	LOF	↔HS^g↔IS^g [139]	↔HS^g↔IS^g [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.