Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity

Table 1 Baseline characteristics of teen-longitudinal assessment of bariatric surgery participants, n = 135

Characteristics	Mean (SD)/n (%)
Age (yr)	16.86 (1.53)
BMI (kg/m2)	53.80 (9.81)
Weight loss prior to surgery (kg)	0.69 (8.36)
Sex
Female	99 (73.33)
Male	36 (26.67)
Race (binary)
White or Caucasian	93 (68.89)
Others	42 (31.11)
Parents’ income
< $25000	53 (39.26)
$25000-$74999	57 (42.22)
≥ $75000	25 (18.52)
NAFLD
NAFL	51 (37.78)
Borderline NASH	22 (16.30)
Definite NASH	8 (5.93)
No NAFLD	54 (40.00)
Fibrosis
Presence	26 (19.26)
None	109 (80.74)
Ballooning degeneration
Many, prominent	5 (3.70)
Less characteristics	16 (11.86)
None	114 (84.44)
Lobular inflammation
Presence	97 (71.85)
None	38 (28.15)

BMI: Body mass index; NAFL: Nonalcoholic fatty liver; NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis.

Table 2 Pathway analysis for miRNA associated with multiple histological features of non-alcoholic fatty liver disease in teen-longitudinal assessment of bariatric surgery participants

Disease and functions	miRNA
Apoptosis of tumor cell lines	miR-122-5p, miR-193b-5p, miR-199b-5p, miR-323-3p
Migration of cells	miR-122-5p, miR-193a-5p, miR-199b-5p
Apoptosis of myeloma cell lines	miR-122-5p, miR-193a-5p
Dedifferentiated liposarcoma	miR-193a-5p, miR-199b-5p
Production of hepatitis C virus	miR-122-5p
Decay of RNA	miR-122-5p
Metastatic hepatocellular carcinoma	miR-122-5p
Replication of viral replicon	miR-122-5p
Invasion of hepatoma cell lines	miR-122-5p
Chemosensitivity of squamous cell carcinoma cell lines	miR-193a-5p
Epithelial-mesenchymal transition of adenocarcinoma cell lines	miR-193a-5p
Migration of adenocarcinoma cell lines	miR-193a-5p
Congenital adrenal hyperplasia	miR-199b-5p
Chronic hepatitis B	miR-199b-5p
Early-stage invasive cervical squamous cell carcinoma	miR-199b-5p
Proliferation of myeloma cell lines	miR-199b-5p

A total of 16 miRNA were included as input for independent practice association. To ensure reliability and relevance of results, we specifically extracted pathways that were experimentally confirmed in human studies, considering only those with P < 0.05.

Table 3 Molecular pathways of non-alcoholic fatty liver disease-associated miRNA in teen-longitudinal assessment of bariatric surgery participants

miRNA	Target	Function
miR-122	SIRT-1[73]; FOXO3[74]	miR-122 downregulates SIRT-1 and induces steatosis and hepatic lipogenesis in NAFLD[73]; miR-122-5p inhibits FOXO3 to attenuate inflammatory response and oxidative stress damage in NAFLD[74]
miR-125b	TNFAIP3[79]	miR-125b targets TNFAIP3 and promotes the NF-κB-mediated inflammatory response in NAFLD[79]
miR-146a	MED1[75]	miR-146a targets MED1 and improves hepatic lipid and glucose metabolism in NAFLD[75]
miR-181a	PPARα[76]	miR-181a inhibits PPARα and aggravates lipid accumulation in hepatocytes[76]
miR-22	SIRT-1[78]	miR-22 targets SIRT-1 and inhibits gluconeogenesis[78]
miR-34a	TGF-β1/Smad3[80]	miR-34a-5p targets TGF-β1/Smad3 and inhibits liver fibrosis in hepatic stellate cells[80]
miR-375	RAC1[81]	miR-375 inhibits RAC1 and alleviates liver fibrosis[81]

FOXO3: Forkhead box O 3; SIRT-1: Sirtuin 1; TNFAIP3: Tumor necrosis factor alpha-induced protein 3; MED1: Mediator complex subunit 1; PPARα: Peroxisome proliferator-activated receptor-α; TGF-β1: Transforming growth factor-β1; Smad3: Mothers against decapentaplegic family 3; RAC1: Rac family small GTPase 1; NAFLD: Non-alcoholic fatty liver disease.