Table 3.

Summary of miRNAs and their validated targets changed by MetS, obesity, hyperlipidemia and hypercholesterolemia, involved in lipid metabolism and described in Section 3.3.

miRNA	Up/Down Regulation	Validated Target	Summary	Human (H)/Rodent (R)/In Vitro/In Vivo Study Model	Ref.
miR-25	DOWN	NOX4	Observed upon hypercholesterolemia in rat hearts leading to diastolic dysfunction and OxS/NS	R, in vivo R, in vivo, in vitro	[21]
47 miRNAs	UP	-	In hypercholesterolemic hearts microarray analysis reported upregulated miRNAs (e.g., miR-133b, miR-101a, miR-29b, miR-223, miR-21) and downregulated miRNAs (e.g., miR-93, miR-25)	R, in vivo	[329]
and
10 miRNAs	DOWN	-
miR-125b-1-3	-	-	Hypercholesterolemia prevented increase of the miRNA after ischemic preconditioning	R, in vivo	[328]
miR-98	DOWN	SREBP-2	Observed in hypercholesterolemic patients (serum and liver). miR-98 overexpression elicited decline of SREBP, LDLR, and HMGCR in mice	H, R, in vivo	[330]
miR-92	UP	SIRT1, KLF2, KLF4	-H2O2, Ang II, and ox-LDL increased miR-92 and SREBP-2 in HUVECs, promoted targeting of SIRT1, KLF2/4 changing NOS-NO bioavailability and endothelial innate immunity	H, R, zebrafish, in vivo	[331]
			-High cholesterol diet elicited SREBP-2-dependent increase of miR-92
miR-379	UP	-	Serum level positively correlated with high cholesterol, predicted to target numerous genes critical for metabolism	H, in vivo	[332]
miR-27a	UP	HMGCR	-Hypoxia induces Egr-1/miR-27a axis, leading to downregulation of HMGCR.	R, in vivo	[334]
			–upregulated also in livers of 3 mice models of MetS
			-HMGCR targeting was proved in various mammalian species-derived cell lines
miR-30c	-	-	In livers of Apoe−/− mice fed a Western diet, miR-30c mimic triggered decrease of cholesterol levels and putative target genes (Elovl5, Mttp, QKI, LPGAT1)	R, in vivo	[335]
	-	LPGAT1, MTP	These expression changes elicit induction of hepatic lipid synthesis and apoB secretion. It may serve as an anti-hyperlipidemic as well as anti-atherosclerotic molecule	R, in vivo	[336]
miR-155-5p	UP	Mafb	Increased by hyperlipidemia to adapt β-cells to IR. Triggered reduction of IL-6 and consequent inhibition of intra-islet production of GLP-1	H, in vitro and R, in vivo, in vitro	[337]
miR-24	UP	SR-BI	-Increased in livers under obesity and hepatocytes under hyperlipidemic conditions	H, in vitro and R, in vivo	[338]
			–deteriorates HDL uptake and affects lipid metabolism
miR-125a miR-455	-	SR-BI	miRNAs involved in negative regulation of HDL cholesteryl ester (HDL-CE) uptake	R, in vivo, in vitro	[342]
miR-125a	DOWN	Elovl6	Decreased by obesity in liver, yet, if overexpressed ameliorates hepatic steatosis, lipid accumulation and increases insulin sensitivity	R, in vivo	[343]
miR-24 miR-30d miR-146a	UP	-	Increased in abdominal AT in obese and T2DM subjects, potentially coregulated due to strong positive correlation among them. Positively correlated with SFRP-4	H, in vivo	[344]
miR-146a	-	TRAF-6	-miR-146 knockout mice were protected from MetS upon HFD via influencing PI3K/AKT/mTOR axis.	R, in vivo	[346]
			–by targeting TRAF-6, miR-146a regulates ATM inflammation
miR-128	UP	INSR	Increase elicited upon VAT hypoxia and suggested to participate in induction of systemic IR	H, R, in vivo, in vitro	[349]
miR-122	UP	Agpat1, Dgat1	FFA increase miR-122 in mice liver via RORα-dependent way. miR-122 is then secreted to increase AT and muscle TG synthesis by targeting Agpat1 and Dgat1	R, in vivo	[355]
	-	-	Therapy with anti-miR-122 results in lower levels of cholesterol	R, in vivo	[356]
	-	KLF3	miR-122 knockout mice showed declined expression of MTTP, leading to disturbance of lipid profile (e.g., VLDL secretion). KLF3 is a another gene critical for liver homeostasis and associated with miR-122	R, in vivo	[357]
miR-132	UP	SIRT1, PTEN, P300, FOXO3, CYP2E1	Regarded as key player in hepatic lipid homeostasis, may serve as human and mice biomarker of NAFLD and NASH. Its overexpression was accompanied by decline of its earlier validated targets	H, R, in vivo	[359]
miR-302	DOWN	ABCA1	Reduced by ac-LDL and ox-LDL, mediating increased cholesterol efflux to macrophages	H, in vivo and R, in vivo	[365]
	UP	MCL-1	Increased by hypoxia/reoxygenation injury, triggering apoptosis of cardiomyocytes	R, in vitro	[366]
miR-181d	DOWN	ANGPTL3	Downregulated in serum and AT of obese subjects and negatively correlated with TG. Increased ANGPTL3 represses lipolysis via LPL	H, in vivo	[368]
miR-181a	UP	GPx-1	Increased by H2O2 in cardiomyocytes	R, in vitro	[22]
miR-144-3p	UP	KLF3, CtBP2	Increased in AT of obese mice, positively impacts adipogenesis (releases C/EBPα from KLF3, CtBP2) and fatty acid synthesis and decreases genes of FAO	R, in vivo, in vitro	[369]