Nonalcoholic Fatty Liver Disease: Focus on Lipoprotein and Lipid Deregulation

Table 1

The physiologic role of all receptors and enzymes described in the paper and their association with insulin resistance and pathogenesis of NAFLD.

Gene symbol	Name	Physiological role	Insulin resistance	Deregulation in NAFLD	Loss-of-function models and NAFLD	Polymorphisms associated with NAFLD	Reference
CETP	Cholesteryl ester transfer protein	Facilitates the transfer of TG from VLDL to LDL and CE from LDL to VLDL	Increased	Increased		+	[18–20]
HL	Hepatic lipase	Facilitates the clearance of TG from VLDL, increases formation of sdLDL	Increased				[21]
LPL	Lipoprotein lipase		Decreased	Decreased			[20]
APOC-3	Apolipoprotein C-3	Inhibitor of lipoprotein lipase	Increased	Increased			[20, 22]
LDLR	LDL receptor	LDL intake		Decreased			[23]
MTTP	Microsomal triglyceride transfer protein	Formation of VLDL in the liver		Decreased	Develop NAFLD	+	[24–26]
SORT 1	Sortilin 1	Intracellular sorting receptors for apolipoprotein B100 lipoproteins				+	[27–29]
PCSK9	Proprotein convertase subtilisin/kexin type 9	Enhances LDLR degradation			Resistance		[30, 31]
HSL	Hormone-sensitive lipase	Adipose tissue lipolysis	Increased	Increased	Resistance		[32, 33]
CD-36	Fatty acid translocase; scavenger receptors	FA uptake; oxidized LDL uptake	Increased	Increased	Protective		[34–40]
FASN	Fatty acid synthase	Catalyzes the last step in fatty acid biosynthesis		Increased	Protective		[41]
ACC	Acetyl coenzyme A (acetyl-CoA) carboxylase	Fatty acid biosynthesis			Protective		[42, 43]
SCD1	Stearoyl-CoA desaturase	Fatty acid desaturation			Protective		[44, 45]
ELOVL6	Elongation of long-chain fatty acids	Fatty acid elongation			Protective		[46]
FADS1 FADS2	Δ-5 and Δ-6 desaturase	PUFA desaturation	Decreased				[47, 48]
SREBP-1c	Sterol regulatory element binding protein 1c		Increased	Increased	Protective		[49, 50]
ChREBP	Carbohydrate regulatory element binding protein		Increased	Increased	Protective		[51]
SIK2	Serine/threonine salt-inducible kinase 2	Increases ChREBP			Protective		[52]
CPT-1	Carnitine palmitoyl transferase-1	Shuttles fatty acids into mitochondria, fatty acid oxidation	Decreased				[53, 54]
DGAT2	Diacylglycerol acyltransferase 2	Triglyceride biosynthesis	Increased	Increased/decreased in NASH	Improves steatosis, aggravates NASH		[55–57]
ATGL	Adipose triacylglycerol lipase	Performs the first step in TAG lysis		Decreased	leads to steatosis		[58, 59]
CGI-58	Gene identification-58	ATGL coactivator			leads to steatosis		[60]
SREBP-2	Sterol regulatory element binding protein 1c	Induces cholesterol synthesis		Decreased			[23, 61]
LXR	Liver X receptor	Induces cholesterol secretion and FA synthesis, induces CD-36 and Idol	Increased	Increased			[62–64]
Idol	Inducible degrader of the LDLR	Idol catalyzes the ubiquitination of LDLR and targets it for degradation	Increased	Increased			[65]
ACAT2	Acyl-Coenzyme A: cholesterol acyltransferase	Cholesterol esterification; provides esterified cholesterol for incorporation into VLDL and storage			Protection		[66]
NPC1L1	Niemann-Pick C1-like 1	Cholesterol absorption			Protection		[67, 68]