Objective:We aimed to investigate the independent and combined associations of grip strength and chair-rising time with cardiovascular disease (CVD) risk among middle-aged and older adults across different glycemic status groups. Methods:This study included 7,258 CVD-free middle-aged and older adults from the China Health and Retirement Longitudinal Study (CHARLS). Muscle strength was assessed based on grip strength and chair-rising time. Incident CVD was defined as a physician-diagnosed heart disease and/or stroke. Cox proportional hazard models and restricted cubic spline analyses were used to quantify the association between muscle strength and CVD. Results:During a mean follow-up of 7.8 years, 1,785 participants (24.6%) developed incident CVD. Both lower normalized grip strength and longer chair-rising time were independently associated with increased CVD risk in a dose-dependent manner ( P for trend < 0.001), with adjusted hazard ratios ( HRs) of 1.37 (95% CI: 1.17-1.61) for the lowest vs. highest grip strength quartile and 1.53 (95% CI: 1.32-1.77) for the longest vs. shortest chair-rising time quartile. The combination of weakest grip and slowest chair-rising time conferred the highest risk ( HR = 2.12; 95% CI: 1.65-2.73). Lower grip strength and prolonged chair-rising time were associated with elevated CVD risk across all glycemic status groups. The association with grip strength reached statistical significance in the normal glucose regulation and prediabetes groups, with a similar point estimate observed in the diabetes group ( P for interaction = 0.622). Conclusion:This study revealed a dose-dependent association between muscle strength and the incidence of CVD. The associations between lower grip strength and prolonged chair-rising time with higher CVD risk were directionally consistent across the glycemic status groups, although not all strata reached statistical significance.

BACKGROUND: Methyltransferase-like 16 (METTL16) is a recently identified m6A RNA methyltransferase. Although its role in hepatocellular carcinoma has been explored, its function in metabolic dysfunction-associated steatotic liver disease (MASLD) remains elusive. METHODS: Expression profiles of methylation-related genes were analyzed in a cohort comprising 206 MASLD patients and 10 healthy controls. Functional assays were conducted using MASLD cell models and diet-induced mouse models. Bioinformatic analyses were performed to evaluate immune cell infiltration and signaling pathway activation. Potential transcriptional regulators and small-molecule inhibitors of METTL16 were predicted through multiple databases. RESULTS: METTL16 expression was markedly upregulated in MASLD tissues and closely correlated with lipid metabolism-related pathways. Knockdown of METTL16 alleviated hepatic steatosis, insulin resistance, and fibrosis in high-fat diet-fed mice. Mechanistically, cell death-inducing DFF45-like effector family members A (CIDEA) was identified as a downstream mediator of METTL16-driven hepatic steatosis. Elevated hepatic METTL16 expression was associated with increased infiltration of innate immune cells, activation of immune-related signaling pathways, and upregulated expression of pro-fibrotic genes. Database mining further revealed that METTL16 may regulate immune-associated genes at both transcriptional and post-transcriptional levels. Additionally, EGR1 and MYC were identified as potential upstream transcriptional regulators of METTL16, and eleven small molecules were predicted to bind to and inhibit its biological activity. CONCLUSION: METTL16 promotes hepatic steatosis and immune-mediated fibrogenesis in MASLD. Targeting the METTL16-CIDEA axis or inhibiting METTL16 activity may serve as a promising therapeutic strategy for the treatment of MASLD.

Tumor necrosis factor α-induced protein 3 (TNFAIP3) has been implicated in various liver diseases, but its role in metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. We analyzed TNFAIP3 expression in diet-induced MASLD mouse models using public transcriptomic data. In vitro, we investigated the effects of TNFAIP3 overexpression and knockdown in HepG2 cells on lipid accumulation, autophagy, and key metabolic pathways. In vivo, a high-fat diet-induced mouse model was used to validate the protective role of TNFAIP3. TNFAIP3 was consistently upregulated in the livers of various MASLD mouse. Overexpression of TNFAIP3 in HepG2 cells reduced lipid droplet accumulation, whereas knockdown aggravated lipid deposition. TNFAIP3 enhanced autophagy by stabilizing ATG4B, and this effect was autophagy-dependent. In vivo, TNFAIP3 overexpression alleviated hepatic steatosis, improved insulin sensitivity, and modulated lipid metabolism-associated pathways. These effects were reversed by autophagy inhibitors. Furthermore, TNFAIP3 upregulation was driven by NF-κB signaling, as inhibition of NF-κB decreased TNFAIP3 levels. The NF-κB–TNFAIP3 axis regulates hepatic lipid metabolism and protects against liver injury in MASLD, primarily through autophagy. These findings suggest that TNFAIP3 could serve as a potential therapeutic target for MASLD and other metabolic liver diseases.

Purpose:This cross-sectional study aimed to investigate the association of complete blood count parameters and lipid metabolism‑related inflammatory indices with early vascular aging (EVA). Methods:A total of 1114 participants were included with an overall EVA prevalence of 19.6%. Logistic regression was adopted to assess the independent associations of neutrophil to high-density lipoprotein cholesterol ratio (NHR) and platelet to high-density lipoprotein cholesterol ratio (PHR) with EVA after adjusting for traditional cardiovascular risk factors. Restricted cubic spline (RCS) models were applied to examine nonlinear relationships. Subgroup analyses were conducted to evaluate effect modification, and decision curve analysis (DCA) was used to assess the net benefit for risk stratification. Results:In the fully adjusted model, both NHR (OR = 1.583, 95% CI: 1.078-2.327, P = 0.019) and PHR (OR = 2.050, 95% CI: 1.325-3.173, P = 0.001) remained independently associated with increased odds of EVA. The RCS analysis did not reveal significant nonlinear relationships for either biomarker (P for non-linearity > 0.05), suggesting that the associations were adequately captured by linear models. Subgroup analyses revealed that the positive association between NHR and EVA risk was more pronounced in men and smokers. For PHR, there was no significant interaction among different subgroups. DCA demonstrated that both NHR and PHR conferred modest net benefit gains (maximum 0.0127 and 0.0162, respectively) across clinically relevant threshold probabilities. Conclusion:In this cross‑sectional population, both NHR and PHR were independently associated with EVA, with essentially linear dose‑response relationships. The association between NHR and EVA was particularly significant in men and smokers, showing population heterogeneity. Both indices provided a modest net benefit for identifying individuals with EVA, but the modest magnitude of this benefit suggests limited immediate clinical utility. Limitations include the cross‑sectional design and single‑center cohort, which limit causal inference and generalizability. Further prospective, multi‑center studies are needed to validate these findings.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusion : s: In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Background:Sex differences in blood pressure (BP) levels and hypertension are important and the role of socioeconomic status (SES) in sex differences in hypertension remains unclear. Objective:This study aimed to evaluate the impact of SES on sex differences of hypertension in a nationally representative survey study. Methods:A total of 98,658 participants aged ≥18 years who have lived in their current residence for ≥6 months were recruited from 162 study sites across mainland China. Sex was self-reported. Individual-level SES included the highest level of education and annual household income. Area-level SES included economic development status, urban/rural residency, and north/south location. Outcomes included levels of systolic and diastolic BP, and hypertension. Linear and Cox regression models were used to examine the associations between sex (women vs men) and BP characteristics stratified by individual or combined SES indicators. Results:Systolic and diastolic BP levels and the prevalence of hypertension were higher in men than in women. This sex difference was found across categories of SES with widened sex disparities in participants having more favorable SES. Significant multiplicative interaction effects of SES on the association of sex with BP characteristics were found. Women with improving SES were associated with lower BP and hypertension prevalence compared to men. For combined SES, a 9% (prevalence ratio 0.91, 95% CI 0.83-0.98) and a 30% lower probability (prevalence ratio 0.70, 95% CI 0.63-0.78) of having hypertension were found in women with an overall intermediate SES and high SES, respectively, compared to those with low SES, while no significant reduction was found in men. Conclusions:There are significant sex differences in BP characteristics and SES has a potent impact on the disparities. Sex-specific public health policies to alleviate socioeconomic inequalities, especially in women are important for the prevention of hypertension.

Obesity results in hepatic fat accumulation, i.e., steatosis. In addition to fat overload, impaired fatty acid β-oxidation also promotes steatosis. Fatty acid β-oxidation takes place in the mitochondria and peroxisomes. Usually, very long-chain and branched-chain fatty acids are the first to be oxidized in peroxisomes, and the resultant short chain fatty acids are further oxidized in the mitochondria. Peroxisome biogenesis is regulated by peroxin 16 (PEX16). In liver-specific PEX16 knockout (Pex16Alb-Cre) mice, hepatocyte peroxisomes were absent, but hepatocytes proliferated, and liver mass was enlarged. These results suggest that normal liver peroxisomes restrain hepatocyte proliferation and liver sizes. After high-fat diet (HFD) feeding, body weights were increased in PEX16 floxed (Pex16fl/fl) mice and adipose-specific PEX16 knockout (Pex16AdipoQ-Cre) mice, but not in the Pex16Alb-Cre mice, suggesting that the development of obesity is regulated by liver PEX16 but not by adipose PEX16. HFD increased liver mass in the Pex16fl/fl mice but somehow reduced the already enlarged liver mass in the Pex16Alb-Cre mice. The basal levels of serum triglyceride, free fatty acids, and cholesterol were decreased, whereas serum bile acids were increased in the Pex16Alb-Cre mice, and HFD-induced steatosis was not observed in the Pex16Alb-Cre mice. These results suggest that normal liver peroxisomes contribute to the development of liver steatosis and obesity.

BACKGROUND:Bile acids (BAs) are closely related to nutrient supply and modified by gut microbiota. Gut microbiota perturbations shape BA composition, which further affects host metabolism. METHODS:We investigated BA profiles in plasma, feces, and liver of mice fed ad libitum, fasted for 24 h, fasted for 24 h and then refed for 24 h using ultraperformance liquid chromatography coupled to tandem mass spectrometry. Gut microbiota was measured by 16S rRNA gene sequencing. Expressions of BA biosynthesis-related genes in the liver and BA reabsorption-related genes in the ileum were analyzed. FINDINGS:Compared with the controls, unconjugated primary BAs (PBAs) and unconjugated secondary BAs (SBAs) in plasma were decreased whereas conjugated SBAs in plasma, unconjugated PBAs, unconjugated SBAs and conjugated SBAs in feces, and unconjugated SBAs in liver were increased in the fasting mice. The expression of BA biosynthesis-related genes in the liver and BA reabsorption-related genes in the ileum were decreased in the fasting mice compared with the controls. Compared with the controls, Akkermansia, Parabacteroides, Muribaculum, Eubacterium_coprostanoligenes and Muribaculaceae were increased in the fasting mice whereas Lactobacillus and Bifidobacterium were decreased. All these changes in BAs and gut microbiota were recovered under refeeding. Akkermansia was negatively correlated with plasma levels of unconjugated PBAs, unconjugated SBAs and glucose, whereas it was positively correlated with plasma conjugated SBAs, fecal unconjugated PBAs, and fecal unconjugated SBAs. CONCLUSIONS:We characterized the BA profiles, gut microbiota, and gene expression responsible for BA biosynthesis and intestinal reabsorption to explore their rapid changes in response to food availability. Our study highlighted the rapid effect of nutrient supply on BAs and gut microbiota.

BACKGROUND AND AIMS:The American Heart Association (AHA) updated the construct and algorithm of cardiovascular health (CVH) recently. We aimed to explore the relationship between the new CVH score and the development of non-alcoholic fatty liver disease (NAFLD). METHODS AND RESULTS:3266 adults free of NAFLD identified via ultrasound were recruited in this prospective study. A modified AHA "Life's Essential 8" (mLE8, i.e., physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure) were collected to evaluate the CVH score. Then participants were categorized into low, moderate, and high CVH subgroups based on overall mLE8 CVH score. According to modified Life's Simple 7 (mLS7) CVH construct, participants were also subdivided into poor, intermediate, and ideal CVH subgroups. During a median 4.3 years follow-up, 623 incident cases of NAFLD were recorded. Compared to those with high CVH, participants with low CVH (adjusted OR = 2.56, 95% CI 1.55-4.24) and moderate CVH (adjusted OR = 1.83, 95% CI 1.17-2.85) had a significantly increased risk of incident NAFLD. Participants with poor CVH (mLS7) but without low CVH (mLE8) did not show a significant elevated risk of incident NAFLD (P = 0.1053). A significant trend was found between increased changes in mLE8 score and a lower risk of NAFLD occurrence. CONCLUSION:Our findings suggested high mLE8 CVH score was associated with a lower risk of NAFLD incidence. The new CVH construct showed a more reasonable classification of CVH status and was more robust in association with NAFLD risks compared with the original one.

Non-alcoholic fatty liver disease (NAFLD) is a chronic non-communicable disease. It is a metabolic syndrome (MS) in the liver. Menopause is a physiological phenomenon of women due to the decline of ovarian function, which is characterized by the deterioration of hypothalamic-pituitary function. Clinical and epidemiological studies have shown that the incidence trend of NAFLD has gender differences and is related to metabolic parameters such as glucose, lipids, and blood uric acid. The incidence of NAFLD in premenopausal women is lower than that in males, while the incidence of NAFLD in postmenopausal women gradually increases to the same as that in males. The mechanism may be mainly related to the changes of sex hormones in postmenopausal women (mainly the decrease of estrogen). The changes of sex hormones such as the decreased levels of estrogen and sex hormone binding globulin (SHBG) and the relatively increased level of androgen can increase the incidence of MS components such as abdominal obesity, abnormal blood lipid metabolism and insulin resistance (IR), making menopause an important independent risk factor for NAFLD in women. Estrogen, androgen receptor antagonists and phytoestrogens can improve hepatic steatosis and IR through many ways, reduce the severity of NAFLD and delay its progression to liver fibrosis, which have certain therapeutic significance for postmenopausal women with NAFLD, but also have some limitations. This paper reviews the research progress in the relationship between menopause and NAFLD in recent years, so as to provide ideas and reference for the prevention and treatment of NAFLD in postmenopausal women.

Previous studies have found that the association between modifiable risk factors and arterial stiffness varied with age. We aimed to explore the age-specific difference in the relationship between new cardiovascular health (CVH) score and arterial stiffness and further detected the age-specific temporal relationships in a prospective cohort study. During a median 4.3 years follow-up, 3757 participants were recruited in this study. A modified AHA “Life’s Essential 8” construct (mLE8 with lacking information on diet habits) was used to evaluate CVH. Branchial-ankle pulse wave velocity (baPWV) was measured to assess arterial stiffness. Data were analyzed with logistic regression models, restricted cubic splines (RCS), and cross-lagged path analysis (age < 60 vs. age ≥ 60). In age-stratified analysis, moderate (OR = 2.21, 95

Abstract Background Bile acids (BAs) are closely related to nutrient supply and modified by gut microbiota. Gut microbiota perturbations shape BA composition, which further affects host metabolism. Methods We investigated BA profiles in plasma, feces, and liver of mice fed ad libitum, fasted for 24 h, fasted for 24 h and then refed for 24 h using ultraperformance liquid chromatography coupled to tandem mass spectrometry. Gut microbiota was measured by 16S rRNA gene sequencing. Expressions of BA biosynthesis‐related genes in the liver and BA reabsorption‐related genes in the ileum were analyzed. Findings Compared with the controls, unconjugated primary BAs (PBAs) and unconjugated secondary BAs (SBAs) in plasma were decreased whereas conjugated SBAs in plasma, unconjugated PBAs, unconjugated SBAs and conjugated SBAs in feces, and unconjugated SBAs in liver were increased in the fasting mice. The expression of BA biosynthesis‐related genes in the liver and BA reabsorption‐related genes in the ileum were decreased in the fasting mice compared with the controls. Compared with the controls, Akkermansia, Parabacteroides, Muribaculum, Eubacterium_coprostanoligenes and Muribaculaceae were increased in the fasting mice whereas Lactobacillus and Bifidobacterium were decreased. All these changes in BAs and gut microbiota were recovered under refeeding. Akkermansia was negatively correlated with plasma levels of unconjugated PBAs, unconjugated SBAs and glucose, whereas it was positively correlated with plasma conjugated SBAs, fecal unconjugated PBAs, and fecal unconjugated SBAs. Conclusions We characterized the BA profiles, gut microbiota, and gene expression responsible for BA biosynthesis and intestinal reabsorption to explore their rapid changes in response to food availability. Our study highlighted the rapid effect of nutrient supply on BAs and gut microbiota.

Abstract Background Low‐density lipoprotein cholesterol (LDL‐C) and diabetes mellitus are both modifiable risk factors for cardiovascular disease; however, whether elevated LDL‐C levels confer a risk for diabetes remains unclear. Objective We aimed to examine the association between serum LDL‐C concentrations at baseline and the risk of developing diabetes at follow‐up in the general population of Chinese adults. Methods This study included 5274 adults aged ≥ 40 years from a community cohort who were without diabetes and followed for a median of 4.4 years. A standard 75‐g oral glucose tolerance test was conducted at baseline and follow‐up visits to diagnose diabetes. Logistic regression models and a restricted cubic spline were used to examine the association between baseline serum LDL‐C levels and the risk of diabetes development. Subgroup analyses were conducted stratifying on age, sex, body mass index, hypertension, family history of diabetes, and LDL‐C levels. Results A total of 652 participants (12%) developed diabetes during the follow‐up period. Compared to quartile 1 of serum LDL‐C, quartiles 2, 3, and 4 were associated with a 30%, 33%, and 30% significantly higher risk of diabetes, respectively after adjustment for confounders including homeostatic model assessment for insulin resistance. The linear relationship between baseline LDL‐C down to 30.1 mg/dL and incident diabetes was demonstrated by restricted cubic spline analysis, and each 1‐SD increase in LDL‐C concentration (28.5 mg/dL) was associated with a 12% increase in the risk of diabetes (odds ratio 1.12, 95% confidence interval 1.03–1.22). Conclusion In this community‐based general population, higher serum LDL‐C levels were linearly associated with an elevated risk of incident diabetes.

BACKGROUND:Low-density lipoprotein cholesterol (LDL-C) and diabetes mellitus are both modifiable risk factors for cardiovascular disease; however, whether elevated LDL-C levels confer a risk for diabetes remains unclear. OBJECTIVE:We aimed to examine the association between serum LDL-C concentrations at baseline and the risk of developing diabetes at follow-up in the general population of Chinese adults. METHODS:This study included 5274 adults aged ≥ 40 years from a community cohort who were without diabetes and followed for a median of 4.4 years. A standard 75-g oral glucose tolerance test was conducted at baseline and follow-up visits to diagnose diabetes. Logistic regression models and a restricted cubic spline were used to examine the association between baseline serum LDL-C levels and the risk of diabetes development. Subgroup analyses were conducted stratifying on age, sex, body mass index, hypertension, family history of diabetes, and LDL-C levels. RESULTS:A total of 652 participants (12%) developed diabetes during the follow-up period. Compared to quartile 1 of serum LDL-C, quartiles 2, 3, and 4 were associated with a 30%, 33%, and 30% significantly higher risk of diabetes, respectively after adjustment for confounders including homeostatic model assessment for insulin resistance. The linear relationship between baseline LDL-C down to 30.1 mg/dL and incident diabetes was demonstrated by restricted cubic spline analysis, and each 1-SD increase in LDL-C concentration (28.5 mg/dL) was associated with a 12% increase in the risk of diabetes (odds ratio 1.12, 95% confidence interval 1.03-1.22). CONCLUSION:In this community-based general population, higher serum LDL-C levels were linearly associated with an elevated risk of incident diabetes.

BackgroundSome circulating proteins are linked to central adiposity. Gremlin 2 (GREM2) functions as a secreted factor involved in osteogenesis and adipogenesis. Here, we investigated the association of blood GREM2 levels and central adiposity, and the biological roles of GREM2 in the browning program of visceral preadipocytes.MethodsThree independent cohorts were applied to detect circulating GREM2 levels. Recombinant Grem2 protein, Grem2 overexpression and knockout mouse models, and preadipocyte-specific Bmpr2 knockout mice were used to assess the roles of Grem2 in the browning program.FindingsWe detected the presence of GREM2 protein in human serum using an ELISA approach. We revealed elevated GREM2 levels in severely obese subjects and validated this finding in a large-scale community population involving 10,327 subjects. Notably, serum GREM2 was positively associated with visceral fat volume, as quantified by 3D reconstruction methods. In mice, Grem2 was highly expressed in visceral fat and liver tissues, while surgical removal of visceral fat lowered circulating Grem2 levels. Visceral fat secreted more Grem2 in obese mice. Grem2-overexpressed mice exhibited a reduced browning ability of visceral fat, whereas Grem2 ablation enhanced the browning capacity and reduced visceral fat content. Mechanistically, Grem2 attenuated the browning program of visceral preadipocytes partially by antagonizing BMP4/7-SMAD1/5/8 signaling pathway. Further, genetic deletion of Bmpr2 in Pdgfrα+ preadipocytes abolished the antagonistic effect of Grem2.InterpretationThese findings indicate that GREM2 might function as a circulating protein factor associated with human visceral adiposity, and Grem2 inhibits the browning capacity of visceral preadipocytes partially by BMP4/7-BMPR2 signaling pathway.FundingThe complete list of funders can be found in the Acknowledgement section.

BackgroundMetabolic dysfunction is known to be associated with arterial stiffness. However, the risks of metabolic syndrome and diabetes due to arterial stiffness and the potential mechanism remain unclear. We aimed to investigate the association of arterial stiffness with the risk of metabolic syndrome and diabetes, and determine whether this association is mediated by liver fat.MethodsA prospective study was conducted with 4,139 Chinese adults who were metabolically healthy at baseline. Arterial stiffness was measured by brachial–ankle pulse wave velocity (baPWV). Obesity was defined as body mass index ≥25 kg/m2. The primary outcomes were incident metabolic syndrome and diabetes.ResultsDuring a median follow-up of 4.4 years, 1,022 (24.7%) and 354 (9.5%) participants developed metabolic syndrome and diabetes, respectively. Compared with those in the lowest quartile of baPWV, participants in the highest quartile had 85 and 91% higher risks of metabolic syndrome and diabetes [risk ratio (RR) 1.85, 95% confidence interval (CI) 1.41, 2.42 for metabolic syndrome; RR 1.91, 95% CI 1.16, 3.15 for diabetes]. Mediation analyses indicated that fatty liver significantly mediated the association of arterial stiffness with metabolic syndrome and diabetes risk. Specifically, 18.4% of metabolic syndrome and 12.6% of diabetes risk due to arterial stiffness were mediated through fatty liver.ConclusionsArterial stiffness was associated with higher risks of metabolic syndrome and diabetes in individuals with obesity. This association may be partially mediated by fatty liver.

近年来肌少症危险因素的相关研究受到了越来越多的关注.肌少症与非酒精性脂肪性肝病(NAFLD)的发病存在一些相同的病理生理机制,如肥胖、胰岛素抵抗、维生素D缺乏、衰老、缺乏体力活动、慢性炎性反应及一些特定的细胞因子(如肌肉生长抑制素、鸢尾素和瘦素)等均参与了这两种疾病的发病.该文主要就肌少症和NAFLD的共同危险因素作一综述,以期为这两种疾病的临床治疗提供新的思路.

Nonalcoholic fatty liver disease (NAFLD) and colorectal adenomatous polyps are closely associated with the various components of metabolic syndrome. This article summarizes the recent studies on the association between NAFLD and colorectal adenomatous polyps, and the results show that NAFLD is associated with an increased risk of colorectal adenomatous polyps, while related mechanism remains unclear, which may be associated with insulin resistance, chronic inflammatory response, adipokines, and intestinal flora disturbance.

Dickkopp-3 (DKK3) has been identified to play a protection role against atherosclerosis. However, little is known about the relationship between serum DKK3 levels and subclinical coronary atherosclerosis. We aimed to investigate the association of serum DKK3 with coronary stenosis in an asymptomatic Chinese population. A total of 550 Chinese adults aged 40-60 years and without symptoms or histories of cardiovascular diseases were randomly selected to undergo coronary computed tomography angiography. We defined ≥ 50% luminal narrowing as significant coronary stenosis and measured serum DKK3 levels by an enzyme-linked immunosorbent assay (ELISA). Fifty-nine participants had significant coronary stenosis and 223 had < 50% coronary stenosis. Proportions of significant coronary stenosis were 13.7%, 11.4%, and 7.1% in DKK3 tertiles 1-3, respectively (Ptrend = 0.0427). In the univariable multinomial logistic regression model, a decreasing DKK3 tertile was associated with significant coronary stenosis with borderline significance (OR: 1.40; 95% confidence intervals (CI): 0.98-1.99, P = 0.0642). In the multivariable regression model, participants in the lowest DKK3 tertile were associated with a 1.42-fold increased risk of significant coronary stenosis than those in the highest DKK3 tertile (OR: 2.42; 95% CI: 1.10-5.33; P = 0.0279) after adjustment for conventional cardiovascular risk factors. In addition, associations between DKK3 and significant coronary stenosis were consistent among subgroups. However, no significant association was found between serum DKK3 levels and < 50% coronary stenosis. Therefore, we have added to the existing evidence that serum DKK3 is inversely associated with the risk of significant coronary stenosis in asymptomatic middle-aged Chinese.