Molecular mechanisms of noncoding RNA and epigenetic regulation in obesity with consequent diabetes mellitus development

Table 1 Transcription factors and long noncoding RNAs in insulin resistance

Factors related to the development of IR	Names of lncRNAs	Targeted nuclear proteins
Lipogenic activity	H19, MALAT1, MEG3, and MIAT↑	SREBP-1c, PPARγ, and FoxO1
Gluconeogenesis	MEG3 and H19↑	CRTC2/CREB, FoxO1, HNF4A and ATF4
Inflammation and oxidative stress	MALAT1 and H19↑	EZH2 and PRC2
Cellular dysfunction	MEG3, MALAT1 and MIAT↑	N/A

lncRNA: Long noncoding RNA; IR: Insulin resistance; SREBP-1c: Sterol reg-ulatory element binding protein-1c; PPARγ: Peroxisome proliferator-activated receptor γ; FoxO1: Forkhead box protein O1; CRTC2/CREB: CREB-regulated transcription coactivator 2; HNF4A: Recombinant hepatocyte nuclear factor 4α; ATF4：Recombinant activating transcription factor 4; EZH2: Enhancer of zeste homolog 2; N/A: Not applicant.

Table 2 Circulating microRNA in obesity

Tissue or organs	Names of miRNAs	Targeted genes
Adipocytic tissue	miR-155, miR-27a, and miR-34a	SOCS1, PPAR
Liver	miR-99b and miR-155	FGF21, PPAR
Muscle	miR-27a, miR-155, and miR-130b	PPAR, PGC1α
Pancreas	miR-132 and miR-92a	BTG2, PTBP1
Cardiovascular system	miR-29a, miR-410-5p, and miR-194	SMAD7

miRNA: microRNA.

Table 3 The profiles of shared long noncoding RNAs in obesity and diabetes mellitus

lncRNA	Description	Expression in obesity	Expression in DM
SRA	Steroid receptor RNA activator	High	Low in patients with type II diabetic cardiovascular disease[74]
ASMER-1	Adipocyte-associated metabolic related lncRNA 1	High in ScAT	High expression related to IR[20]
ASMER-2	Adipocyte-associated metabolic related lncRNA 2	High in ScAT	High expression related to IR[20]
ADNCR	Adipocyte differentiation-associated lncRNA	Low	Low[23]
HOTAIR	HOX antisense intergenic RNA	High	High[71]
Blnc1	Brown fat lncRNA 1	High in high-fat-diet-fed mice[28]	High in the blood of patients with diabetic nephropathy[82]
H19	LncRNA H19	Low in obesity-associated inflammatory conditions[83]	Low[84]
MALAT1	Metastasis-associated lung adenocarcinoma transcript 1	High[85]	High expression in PBMCs from type 2 diabetes patients[39]

lncRNA: Long noncoding RNA; DM: Diabetes mellitus; ScAT: Subcutaneous adipose tissue; IR: Insulin resistance; PBMC: Peripheral blood mononuclear cell.