Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Objective:To investigate the iodine nutrition level and thyroid function status of pregnant women in Hubei Province.Methods:According to the requirements of "the National Iodine Deficiency Disorders Monitoring Program (2016 Edition)", in 2020, using a cross-sectional survey method, two mountainous counties and two plain areas in Hubei Province were divided into five districts: east, west, south, north, and central. One township (street) was selected from each district, and 20 pregnant women were selected from each township (street) as survey subjects. Urine iodine content and thyroid function indicators [serum free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb)] were tested. Abnormal thyroid function rate and antibody positive rate were analyzed, and correlation analysis of thyroid function indicators was conducted (Spearman method). Results:A total of 321 pregnant women were included, including 43, 114, and 164 in early, middle, and late pregnancy, respectively; The median urinary iodine was 164.80 μg/L. The median serum FT 3, FT 4, TSH, TPOAb, TgAb levels were 4.10, 12.83 pmol/L, 1.85 mU/L, 15.84 and 13.35 U/ml, respectively. There were statistically significant differences in FT 3, FT 4, and TSH levels among different trimesters ( P < 0.05). According to Spearman's correlation analysis, FT 3 in early stage of pregnancy was negatively correlated with TSH and TPOAb levels ( r = - 0.46, - 0.33, P < 0.05), while TSH was positively correlated with TPOAb level ( r = 0.33, P = 0.032); there was a positive correlation between FT 4 and TgAb levels in middle stage of pregnancy ( r = 0.21, P = 0.032); there was a negative correlation between FT 3 and TPOAb levels in late stage of pregnancy ( r = - 0.19, P = 0.017); FT 3 and FT 4, TPOAb and TgAb levels were positively correlated throughout pregnancy ( P < 0.05). There was no correlation between urinary iodine content and thyroid function indicators ( P > 0.05). The total abnormal rate of thyroid function was 7.79% (25/321), with 16.28% (7/43), 5.26% (6/114), and 7.32% (12/164) in early, middle, and late pregnancy, respectively. There was no statistically significant difference in the abnormal rate of thyroid function among different pregnancy periods (χ 2 = 4.83, P = 0.097). The detection rates of hypothyroxinemia, hypothyroidism, subclinical hypothyroidism, hyperthyroidism, and subclinical hyperthyroidism were 4.36% (14/321), 0.31% (1/321), 2.49% (8/321), 0.31% (1/321), and 0.31% (1/321), respectively. The positive detection rate of autospecific antibodies was 10.28% (33/321), with a TPOAb positive detection rate of 9.97% (32/321) and a TgAb positive detection rate of 5.30% (17/321). Conclusions:The iodine nutrition level of pregnant women in Hubei Province is at a suitable level, and the rates of abnormal thyroid function and thyroid autospecific antibody positive are relatively low. It is necessary to continuously monitor the iodine nutrition and thyroid function indexes of pregnant women, strengthen health education on the hazards of iodine deficiency during pregnancy, and minimize the harm to maternal and infant health caused by iodine deficiency.