Table 2.

MicroRNA involved in regulation of brown adipose tissue development and function.

MicroRNA	Target	Function	Experimental Model	Reference	Human Obesity and Related Complications			Reference
					VAT	SAT	Serum
Constitutive brown adipose tissue (cBAT)
miR-193a/b miR-365 cluster	RUNX1T1 Cdo IGFBP5	↑ brown adipogenesis ↓ myogenesis =brown adipogenesis	primary murine brown preadipocytes miR-193b-mutant mice	[74,75]	↓ in obese individuals with NASH	↓in obesity ↑ after bariatric surgery	↓in obesity ↑ in prediabetes ↓ upon exercise	[8,9] [30] [53] [76,77]
miR-328	BACE1	↑ brown adipogenesis ↓ myogenesis ↓ weight gain	primary murine brown preadipocytes DIO mice	[78]	↓ in obese individuals with NASH		↓in obesity	[53] [79,80]
miR-378	PDE1B	↑ brown adipogenesis	ob/ob mice DIO mice	[81]	↓ in obese individuals with NASH	↓in obesity	↑ in insulin resistance	[30] [53] [82]
	adiponectin	↓ adiponectin synthesis	3T3-L1 cells ob/ob mice	[118]	↓in obesity			[119]
miR-203 miR-182	UCP1 PGC1α PPARα Cox7 Cox8	↑ brown adipogenesis ↑ thermogenesis	Dgcr8 -/- mice	[83]	↑in obesity	↓after weight loss		[9] [34]
miR-106b miR-93 cluster	UCP1 PRMD16 PPARα PGC1α	↓ brown adipogenesis ↓ thermogenesis	DIO mice	[84]	↓↑in obesity	↓after weight loss		[9] [30]
Recruitable brown adipose tissue (rBAT)
miR-34a	FGF21 SIRT1	↓ brown adipogenesis ↓adipocyte browning ↓ thermogenesis	3T3-L1 adipocytes DIO mice	[64]	↑in obesity	↑in obesity	↑in insulin resistance	[8] [37] [59] [82]
miR-27b	PPARγ PPARα C/EBPα Prohibitin UCP1 PRMD16, PGC1α	↓ brown adipogenesis ↓adipocyte browning ↓ mitochondrial biogenesis ↓ thermogenesis	human MADS	[86,87,88]	↓ in obese individuals with NASH	↓in obesity		[30] [37] [53]
miR-133	PPARγ PPARα PRMD16, PGC1α	↓ brown adipogenesis ↓adipocyte browning ↓ thermogenesis	murine primary adipocytes C57Bl/6N mice	[90,91]	↑in obesity			[9]
miR-155	C/EBPβ	↓ brown adipogenesis ↓adipocyte browning ↓ thermogenesis ↓ leptin synthesis ↓ resistin synthesis	murine primary adipocytes C57BL/6J mice apoE−/− mice miR-155-/- mice	[6] [92] [126] [128]		↓in diabetic obese individuals	correlates negatively with BMI	[34] [93]
miR-32	Tob1	↑ brown adipogenesis ↑ adipocyte browning ↑ thermogenesis	murine brown preadipocyte WT-1 cells murine primary adipocytes C57BL/6J mice	[7]		↓after weight-loss	=in obesity	[9] [82]
miR-455	RUNX1T1 Necdin HIF1AN	↑ brown adipogenesis ↑ adipocyte browning ↑ thermogenesis	murine brown preadipocytes C3H10T1/2 cells 3T3-L1 cells C57BL/6 mice	[94,95,96]		↑in obesity		[8]
miR-30b/c	Rip140	↑ adipocyte browning ↑ thermogenesis	murine white and brown preadipocytes C57BL/6 mice	[97]		↓in obesity		[30]
miR-129-5p	IGF2 EGR1 FABP4 UCP1 PPARγ	↓ adipogenesis ↓adipocyte browning	murine primary adipocytes db/db mice	[101]			↑in obesity	[101]

↓ downregulation; ↑ upregulation; apoE—apolipoprotein E; Bace1—β-secretase 1; BMI—body mass index; Cdo—surface protein Cdo; C/EBPα—CCAAT/enhancer-binding protein α; C/EBPβ—CCAAT/enhancer-binding protein β; Cox7—cytochrome c oxidase subunit 7; Cox8—cytochrome c oxidase subunit 7; db/db mice—mice homozygous for the diabetes spontaneous mutation; Dgcr8—DiGeorge syndrome critical region 8; DIO—diet-induced obesity; EGR1—early growth factor response 1; FABP4—fatty acid binding protein 4; FGF21—fibroblast growth factor 21; HIF1AN—hypoxia inducible factor 1 subunit alpha inhibitor; IGFBP5—insulin-like growth factor binding protein 5; IGF2—insulin growth factor 2; MADS—multipotent adipose-derived stem cells; ob/ob mice—mice homozygous for the obese spontaneous mutation; PDE1B—phosphodiesterase 1B; PGC1α—peroxisome PPARγ coactivator 1 α; PPARα—peroxisome-proliferator-activated receptor α; PPARγ—peroxisome-proliferator-activated receptor γ; PRMD16—PR domain containing 16; Rip140—receptor-interacting protein 140; RUNXT1T—runt-related transcription factor 1 partner transcriptional co-repressor 1; SAT—subcutaneous adipose tissue; SIRT1—sirtuin 1; Tob1—transducer of erbB2 1; VAT—visceral adipose tissue; UCP1—uncoupling protein 1.