Nonlinear dose-response association of moderate-to-vigorous physical activity with hyperuricemia in US adults: NHANES 2007-2018.

BACKGROUND: The relationship between physical activity and hyperuricemia (HUA) remains inconsistent, and the dose-response association between moderate-to- vigorous physical activity (MVPA) level and HUA still unclear. In this study, we aimed to investigate the dose-response association of MVPA with HUA, and to explore an appropriate range of MVPA level for preventing HUA. METHODS: Data from the US National Health and Nutrition Examination Survey (NHANES) 2007-2018 were used, including 28740 non-gout adult Americans. MVPA level was self-reported using the Global Physical Activity Questionnaire and serum uric acid was measured using timed endpoint method. The dose-response relationship between MVPA level and HUA was modeled with restricted cubic spline analysis. Logistic regression analysis were applied to estimate odd ratios (ORs) and 95% confidence intervals (CIs) of the relationships between MVPA level and HUA. RESULTS: A total of 28740 adults were included in the study (weighted mean age, 47.3 years; 46.5% men), with a prevalence rate of HUA was 17.6%. The restricted cubic spline functions depicted a general U-shaped relationship between MVPA level and HUA. The MVPA level of 933 and 3423 metabolic equivalent (MET) -min/wk were the cut-off discriminating for the risk of HUA. Participants with MVPA levels in the range of 933-3423 MET-min/wk had lower risk of HUA and they had the lowest risk when MVPA levels at around 1556 MET-min/wk. Compared with the moderate-activity group (600-2999 Met-min/wk), the low-activity group (< 600 Met-min/wk) had a greater risk of HUA (OR, 1.13 [95%CI, 1.02-1.26]) after fully adjusting for potential confounders. CONCLUSIONS: Compared with the moderate MVPA level, the low MVPA level was associated with the higher risk of HUA. And there may be a U-shaped dose-response relationship between MVPA level and HUA. When MVPA level was approximately 933-3423 MET-min/wk, the risk of HUA may at a lower level and the risk reached the lowest when MVPA level at around 1556 MET-min/wk.

Association between the traditional Chinese medicine constitution and metabolic dysfunction-associated fatty liver disease in older people: A cross-sectional study.

Background: Few studies have focused on the relationship between the traditional Chinese medicine constitution (TCMC) and metabolic dysfunction-associated fatty liver disease (MAFLD) in older populations. We sought to investigate the distribution of MAFLD and the TCMC in older people, and provide a theoretical basis for TCMC-based management of MAFLD in this population. Methods: A cross-sectional study was conducted among older (≥65 years) individuals in Zhongshan, China. Information on common sociodemographic characteristics, medical history, anthropometric measurements, and the TCMC was collected. The chi-square test, multivariable logistic regression analysis, subgroup analysis, and inverse probability weighting of the propensity score were used to explore the relationship between MAFLD and the TCMC. Results: Of 7085 participants, 1408 (19.9 %) had MAFLD. The three most common TCMC types in MAFLD patients were "phlegm-dampness", "gentleness", and "yin-deficiency". After adjustment for gender, age, tobacco smoking, alcohol consumption, body mass index, abnormal waist-to-hip ratio, hypertension, diabetes mellitus, and dyslipidemia, MAFLD was positively associated with the phlegm-dampness constitution (PDC) (ORadjusted (95 % CI) = 1.776 (1.496-2.108), P < 0.001), and negatively correlated with the qi-depression constitution (0.643 (0.481-0.860), 0.003). A stronger correlation between the PDC and MAFLD was observed in men compared with women (ORadjusted = 2.04 (95%CI = 1.47-2.84) vs. 1.70 (95%CI = 1.39-2.08), Pinteraction = 0.003) as well as between people who smoked tobacco and non-tobacco-smoking individuals (2.11 (1.39-3.21) vs. 1.75 (1.45-2.12), 0.006). Conclusions: A positive relationship was observed between MAFLD and the PDC in older people living in Zhongshan. Early detection and treatment of the PDC (especially in men and smokers) could prevent the occurrence and development of MAFLD.

Insufficient compensatory pancreatic ß-cells function might be closely associated with hyperuricemia in U.S. adults: evidence from the National Health and Nutrition Examination Survey.

BACKGROUND: The prevalence of hyperuricemia (HUA) is gradually increasing worldwide. HUA is closely related to diabetes, but the relationship between HUA and pancreatic ß-cells function in the population is unclear. The purpose of this article is to investigate the association between pancreatic ß-cells and HUA. METHODS: This cross-sectional study examined the association between pancreatic ß-cells and HUA in 1999-2004 using data from the National Health and Nutrition Examination Survey (NHANES). Subjects were divided into two groups: HUA and non-HUA. Pancreatic ß-cells function levels were assessed using homeostasis model assessment version 2-%S (HOMA2-%S), homeostasis model assessment version 2-%B (HOMA2-%B) and disposition index (DI). Multivariate logistic regression models and restricted cubic spline models were fitted to assess the association of pancreatic ß-cells function with HUA. RESULTS: The final analysis included 5496 subjects with a mean age of 46.3 years (standard error (SE), 0.4). The weighted means of HOMA2-%B, HOMA2-%S and DI were 118.1 (SE, 1.0), 69.9(SE, 1.1) and 73.9 (SE, 0.7), respectively. After adjustment for major confounders, participants in the highest quartile of HOMA2-%B had a higher risk of HUA (OR = 2.55, 95% CI: 1.89-3.43) compared to participants in the lowest quartile. In contrast, participants in the lowest quartile of HOMA2-%S were significantly more likely to have HUA than that in the highest quartile (OR = 3.87, 95% CI: 2.74-5.45), and similar results were observed in DI (OR = 1.98, 95% CI: 1.32-2.97). Multivariate adjusted restricted cubic spline analysis found evidence of non-linear associations between HOMA2-%B, HOAM2-%S, DI and the prevalence of HUA. CONCLUSION: Our finding illustrated the indicators of inadequate ß-cells compensation might be a new predictor for the presence of HUA in U.S. adults, highlighting a critical role of pancreatic ß-cells function on HUA.

Associations between metal(loid) exposure with overweight and obesity and abdominal obesity in the general population: A cross-sectional study in China.

Previous studies have revealed links between metal(loid)s and health problems; however, the link between metal(loid)s and obesity remains controversial. We evaluated the cross-sectional association between metal(loid) exposure in whole blood and obesity among the general population. Vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), antimony (Sb), thallium (T1), and lead (Pb) were measured in 3029 subjects in Guangdong Province (China) using ICP-MS. The prevalence of overweight and obesity (OWO) and abdominal obesity (AOB) was calculated according to body mass index (BMI) and waist circumference (WC), respectively. Multivariate analysis showed that elevated blood Cu, Cd, and Pb levels were inversely associated with the risk of OWO, and these associations were confirmed by a linear dose-response relationship. Elevated blood Co concentration was associated with a decreased risk of AOB. A quantile g-computation approach showed a significantly negative mixture-effect of 13 metal(loid)s on OWO (OR: 0.96; 95% CI: 0.92, 0.99). Two metals-Ni and Mo-were inversely associated with the risk of OWO but positively associated with AOB. We cross-grouped the two obesity measurement types and found that the extremes of metal content were present in people with AOB only. In conclusion, blood Cu, Mo, Ni, Cd, and Pb were inversely associated with the risk of OWO. The presence of blood Co may be protective, while Ni and Mo exposure might increase the risk of AOB. The association between metal(loid) exposure and obesity warrants further investigation in longitudinal cohort studies.

The mediation and interaction of the obesity index between moderate-vigorous recreational physical activity and hypertension.

Previous studies showed that physical activity (PA) is concerned with hypertension (HTN). However, the mediation and interaction role of the obesity index: body mass index (BMI), waist-hip ratio (WHR), body fat rate (BFR) and visceral fat index (VFI) between PA and HTN has never been studied. Therefore, the purpose of this study was to assess the mediation and interaction of the obesity index between moderate-vigorous recreational physical activity (MVRPA) and HTN. We conducted a cross-sectional study of 4710 individuals aged 41 or older in Torch Development Zone, Zhongshan City. The mediation and interaction of the obesity index were evaluated by a four-way decomposition. 48.07% of participants had HTN among these groups. In the adjusted linear regression model, MVRPA was significantly correlated with WHR (ß±SE = -0.005±0.002; P<0.05). Compared to sufficient MVRPA (odds ratio (OR) = 1.35), 95% (confidence interval (CI) = 1.17-1.56), insufficient MVRPA increased the risk of developing HTN. Furthermore, there were associations between BMI, WHR, BFR, VFI and HTN where the adjusted ORs and 95% CIs were 1.11 (1.09-1.13), 6.23 (2.61-14.90), 1.04 (1.03-1.06), 1.07 (1.06-1.09), respectively. The mediation analyses suggested that the impact of MVRPA on HTN risk may partly be explained by changes in obesity index, with a pure indirect mediation of WHR between MVRPA and HTN (P<0.05). Therefore, weight control, especially reducing abdominal obesity and maintaining adequate MVRPA, may lead to more proper control of HTN.

Prevalence and trends of developmental disabilities among US children and adolescents aged 3 to 17 years, 2018-2021.

Developmental disabilities prevalence seem to be high in countries around the world. It's worth understanding the most recent prevalence and trends of developmental disabilities. The objective of this study is to examine the prevalence and trends of developmental disabilities of US children and adolescents. A total of 26,422 individuals aged 3-17 years were included. Annual data were examined from the National Health Interview Survey (2018-2021). Weighted prevalence for each of the selected developmental disabilities were calculated. The prevalence of any developmental disabilities in individuals was 16.65% (95% CI 16.03-17.26%), prevalence of attention deficit/hyperactivity disorder (ADHD), learning disability (LD), autism spectrum disorder (ASD), intellectual disability (ID), and other developmental delay were 9.57% (95% CI 9.09-10.06%), 7.45% (95% CI 7.00-7.89%), 2.94% (95% CI 2.67-3.21%), 1.72% (95% CI 1.51-1.93%), and 5.24% (95% CI 4.89-5.59%), respectively. Significant increases were observed for other developmental delay (4.02-6.05%) and co-occurring LD & ID (1.03-1.82%). Findings form this study highlight a high prevalence of any developmental disabilities, although no significant increase was observed. The prevalence of other developmental delay and co-occurring LD & ID were significantly increased. Further investigation is warranted to assess potentially modifiable risk factors and causes of developmental disabilities.

Immune response and safety of inactivated SARS-CoV-2 vaccines during pregnancy: a real-world observational study.

BACKGROUND: As pregnant women are excluded from clinical trials of inactivated SARS-CoV-2 vaccines, it is important to assess the immune response in women receiving the vaccination while unknowingly pregnant. METHODS: In a multicenter cross-sectional study, we enrolled 873 pregnant women aged 18-45 years. Serum antibody levels induced by inactivated vaccines were determined. Adverse events were collected by self-reported survey after vaccination. Logistic regression model and restricted cubic spline model were used to investigate the association of factors with antibody positivity. RESULTS: As the doses of the vaccine increase, neutralizing antibody (NAb) positivity was 98.3%, 39.5%, and 9.5% in pregnant women, respectively. The dose of vaccine and duration since vaccination were associated with NAb positivity. The OR of two and three doses of vaccines were 7.20 and 458.33 (P < 0.05). NAb levels and duration since vaccination showed a linear relationship in pregnant women vaccinated two doses, with a decrease to a near seropositivity threshold at 22 weeks. Adverse events were mainly mild or moderate after vaccinated during pregnancy, with no increase in incidence compared with whom vaccinated during pre-pregnancy. CONCLUSIONS: The use of inactivated vaccines during pregnancy induced favorable immune persistence, and the incidence of adverse events did not increase.

Prevalence and Trends in Diagnosed Learning Disability Among US Children and Adolescents From 1997 to 2021.

This cross-sectional study uses data from the National Health Interview Survey to examine the prevalence of and trends in diagnosed learning disability among US children and adolescents from 1997 to 2021.

The association of periodontal disease and oral health with hypertension, NHANES 2009-2018.

BACKGROUND: Hypertension is a worldwide public health problem. We sought to explore the interaction of oral health and smoking on hypertension, and periodontal disease and smoking on hypertension. METHODS: We included 21,800 participants aged ≧ 30 years from the National Health and Nutrition Examination Survey (NHANES) 2009-2018. Information of oral health and periodontal disease were self-reported. Blood pressure was taken by trained personnel and/or physicians at mobile testing center. Multiple logistic regression was used to estimate the association between oral health, periodontal disease and the prevalence of hypertension. The effects of oral health and periodontal disease on hypertension under smoking status and age were analyzed by stratified and interaction analysis. RESULTS: A total of 21,800 participants were investigated, including 11,017 (50.54%) in hypertensive group and 10,783 (49.46%) in non-hypertensive group. Compared with the excellent/very good of oral health, the multivariable-adjusted OR of good, fair, and poor were 1.13 (95% CI, 1.02-1.27), 1.30 (95% CI, 1.15-1.47), and 1.48 (95% CI, 1.22-1.79) (p for trend < 0.001) for hypertension, respectively. Compared without periodontal disease group, the multivariable-adjusted OR of periodontal disease for hypertension was 1.21 (95% CI ,1.09-1.35) (p for trend < 0.001). Furthermore, we found the interactions between periodontal disease and smoking, oral health and smoking, periodontal disease and age, oral health and age were p < 0.001. CONCLUSIONS: An association between oral health and periodontal disease with the prevalence of hypertension was identified. There exists interactive effect of periodontal disease and smoking, oral health and smoking, periodontal disease and age, oral health and age on hypertension in American population over 30 years of age and older.

Correlation analysis of anthropometric indices and type 2 diabetes mellitus in residents aged 60 years and older.

Background and purpose: In recent years, the incidence of obesity in people aged 60 and over has increased significantly, and abdominal obesity has been recognized as an independent risk factor for diabetes. Aging causes physiologic decline in multiple body systems, leading to changes in obesity indicators such as BMI. At present, the relationship between abdominal obesity markers and Diabetes mellitus (DM) in people aged 60 years and older remains unclear. Therefore, it is necessary to study the correlation between anthropometric indices and diabetes and explore potential predictors. Methods: The basic demographic information of participants aged 60 and above in Zhongshan City in 2020 was collected. Physical parameters, blood glucose and other biochemical indices were measured comprehensively. Binary logistic regression analysis was used to explore the relationship between abdominal obesity indicators [Waist circumference, Neck Circumference, Waist-to-hip ratio, Chinese Visceral Obesity Index (CVAI), and visceral obesity index] and diabetes mellitus. ROC characteristic curve was used to analyze the predictive ability of abdominal obesity indicators to DM, and the non-restrictive cubic spline graph was used to visualize the screened obesity indicators and diabetes risk. Results: Among 9,519 participants, the prevalence of diabetes was 15.5%. Compared with low CVAI, High CVAI level was significantly associated with increased prevalence of DM in males and females (all p < 0.05), in males (OR, 2.226; 95%CI: 1.128-4.395), females (OR, 1.645; 95%CI: 1.013-2.669). After adjusting for potential confounding factors, there were gender differences between neck circumference and the prevalence of DM, and above-normal neck circumference in males was significantly associated with increased prevalence of DM (OR, 1.381; 95% CI: 1.091-1.747) (p < 0.05). Conclusion: Among these anthropometric indices, CVAI is consistent with the features of fat distribution in older individuals and shows superior discriminative power as a potential predictor of DM, compared to traditional anthropometric parameters.

Association Between Dairy Intake and Executive Function in Chinese Children Aged 6-12 Years.

Association between dairy intake and executive function remains controversial, especially among children, a population with fast-developing executive functions. This study aimed to explore this topic. Additionally, we further distinguished the role of dairy intake types (full- or low-fat milk or yogurt) in this relationship. This survey included 5,138 children aged 6-12 years. Dairy intakes were assessed by validated questionnaires. Executive function was measured by the behavior rating inventory of executive function (BRIEF; Parent Version), and lower T-scores of BRIEF indices indicated superior executive function performance. Results showed that children with higher dairy intake had statistically better performance in Shift (46.58 ± 7.48 vs. 45.85 ± 7.10), Initiate (48.02 ± 8.58 vs. 47.14 ± 8.33), and Working Memory (50.69 ± 8.82 vs. 49.89 ± 8.73). In the analysis of multivariate linear regression, we found that for every one unit increase in full-fat dairy intake, T-scores for Shift (ß = -0.350 (95% confidence interval [CI]: (-0.660, -0.039) and Initiate (ß = -0.486 (95% CI: (-0.845, -0.127) were decreased and for every one unit increase in low-fat dairy intake, T-score for Organizations of Materials (ß = -0.940 (95% CI: (-1.690, -0.189) was decreased. After distinguishing dairy into milk and yogurt, we observed that only milk intake, not yogurt, was significantly associated with better executive function performance in Shift (ß = -0.390 (95% CI (-0.745, -0.035) and Initiate (ß = -0.509 (95% CI (-0.917, -0.101) after adjusting for potential confounding factors. This study shows that a higher intake of dairy, irrespective of fat content, is related to better executive function performance among children aged 6-12. In addition, a significantly positive relationship between dairy intake and executive function's indices of Shift and Initiate only was observed in milk, not in yogurt.

Computer-aided directed evolution ofl-threonine aldolase for asymmetric biocatalytic synthesis of a chloramphenicol intermediate.

l-Threonine aldolases (LTAs) employing pyridoxal phosphate (PLP) as cofactor can convert low-cost achiral substrates glycine and aldehyde directly into valuable ß-hydroxy-α-amino acids such as (2R,3S)-2-amino-3-hydroxy-3-(4-nitrophenyl) propanoic acid ((R,S)-AHNPA), which is utilized broadly as crucial chiral intermediates for bioactive compounds. However, LTAs' stereospecificity towards the ß carbon is rather moderate and their activity and stability at high substrate load is low, which limits their industrial application. Here, computer-aided directed evolution was applied to improve overall activity, selectivity and stability under desired process conditions of a l-threonine aldolase in the asymmetric synthesis of (R,S)-AHNPA. Selectivity and stability determining regions were computationally identified for structure-guided directed evolution of LTA-variants under efficient biocatalytic process conditions using 40% ethanol as cosolvent. We applied molecular modeling to rationalize selectivity improvement and design focused libraries targeting the substrate binding pocket, and we also used MD simulations in nonaqueous process environment as an effective and promising method to predict potential unstable loop regions near the tetramer interface which are hot-spots for cosolvent resistance. An excellent LTA variant EM-ALDO031 with 18 mutations was obtained, which showed âˆ¼ 30-fold stability improvement in 40% ethanol and diastereoselectivity (de) raised from 31.5% to 85% through a three-phase evolution campaign. Our fast and efficient data-driven methodology utilizing a combination of experimental and computational tools enabled us to evolve an aldolase variant to achieve the target of 90% conversion at up to 150 g/L substrate load in 40% ethanol, enabling the biocatalytic production of ß-hydroxy-α-amino acids from cheap achiral precursors at multi-ton scale.

Prognostic impact of hepatitis B virus infection in patients with primary cervical cancer.

BACKGROUND: Hepatitis B virus (HBV) infection has been associated with an increased risk of a few malignancies. However, the prognostic impact of HBV infection remains unclear in cervical cancer. OBJECTIVE: To explore the association between HBV infection and survival outcomes of patients with primary cervical cancer, using overall survival (OS) and disease-free survival (DFS) as primary endpoints. METHODS: This analysis was performed retrospectively with newly diagnosed cervical cancer patients admitted to the Department of Gynecologic Oncology at the Sun Yat-sen Memorial Hospital of Sun Yat-sen University from June 2013 to October 2019, who were enrolled and followed up. The Kaplan-Meier method and Cox proportional hazard analysis were used to examine the performance of HBV infection in predicting OS and DFS. RESULTS: Patients were followed up for a median of 37.17 months (95% CI, 34.69-39.65). Among the 695 patients, 87 (12.5%) were serologically positive for hepatitis B surface antigen (HBsAg), and 276 (39.7%) had a prior history of HBV infection. There was no significant difference between HBsAg-positive group and HBsAg-negative patients concerning OS or DFS. Multivariate analysis showed prior HBV infection was an independent favorable prognosticator for OS (HR, 0.335; 95% CI, 0.153-0.0.734; p = 0.006) and DFS (HR, 0.398; 95% CI, 0.208-0.691; p = 0.002). CONCLUSION: We provide the first clinical evidence that suggests prior HBV infection as an independent favorable prognostic factor for patients with primary cervical cancer.

Associations between serum total, free and bioavailable testosterone and non-alcoholic fatty liver disease in community-dwelling middle-aged and elderly women.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is considered both a cause and consequence of the metabolic syndrome (MetS). While emerging evidence has indicated that testosterone is associated with MetS, the relationship between testosterone and NAFLD in women remains unclear. Therefore, this study investigated the associations between serum testosterone levels and NAFLD prevalence risk in a community-based cross-sectional study. METHODS: A total of 2117 adult women were included in the analysis. Serum total testosterone (TT) was measured by chemiluminescence immunoassay, and other testosterone-related indices, such as concentrations and percentages of calculated free testosterone (cFT) and bioavailable testosterone (BioT), and free androgen index (FAI), were also calculated. NAFLD was diagnosed by clinical criteria. Logistic regression was used to explore these associations. RESULTS: There were significant differences in TT, FAI, cFT and BioT between women with and without NAFLD (all P<0.001). Multivariate logistic-regression analyses demonstrated that both absolute concentrations and percentages of cFT and BioT were positively associated with NAFLD risk prevalence in all models. Adjusted ORs (95% CI) for quartile 4 vs quartile 1 of % cFT and % BioT were 5.94 (4.29-8.22) and 5.21 (3.79-7.17) in model 2, and 4.35 (3.07-6.18) and 3.58 (2.55-5.03) in model 3 (all P<0.001 for trend). In addition, quartiles of TT, FAI, cFT and BioT were significantly correlated with degree of hepatic steatosis. ROC analysis also showed that % cFT and % BioT were more accurate for predicting NAFLD prevalence than was TT. CONCLUSION: Serum cFT and BioT were positively associated with NAFLD risk, and elevated levels of cFT and BioT could be independent risk factors of NAFLD prevalence in middle-aged and elderly women.

Lower adropin expression is associated with oxidative stress and severity of nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Adropin has been reported to be involved in metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). However, the clinical relevance of adropin expression to the histological severity of NAFLD is unclear. This study aimed to investigate adropin expression in biopsy-proven NAFLD patients. METHODS: This case-control study enrolled a total of 109 participants, including 15 normal histological controls, 26 nonalcoholic fatty liver (NAFL), 21 nonalcoholic steatohepatitis (NASH) subjects and B-ultrasound NAFLD-free normal controls matched to the cases based on age and sex (the case:control ratio was 1:1). Liver biopsies were obtained and histological characteristics were assessed. Primary murine hepatocytes were isolated from C57BL/6J mice and incubated with doses of palmitate to induce oxidative stress. RESULTS: The serum adropin level in NASH patients was 9.99 ± 5.51 ng/ml, significantly lower than that in B-ultrasound normal controls (22.70 ± 6.32 ng/ml), histological normal controls (21.93 ± 6.63 ng/ml) and NAFL patients (17.82 ± 6.90 ng/ml). Serum adropin levels were negatively correlated with the histological severity of NAFLD. The lower serum adropin level predicted NASH (area under the ROC curve: 87.1%). Adropin expression in serum and liver was also negatively associated with hepatic MDA and serum 8-iso-PGF2α levels. Furthermore, palmitate rather than oleate induced oxidative stress in a dose-dependent manner with a gradient decrease in adropin expression in primary murine hepatocytes. Adropin overexpression or treatment ameliorated palmitate-induced oxidative stress in hepatocytes. CONCLUSIONS: Circulating adropin was inversely associated with the oxidative stress and histological severity of NAFLD. It may play an important role in the development of NAFLD.

Adropin regulates hepatic glucose production via PP2A/AMPK pathway in insulin-resistant hepatocytes.

Adropin as a secretory peptide has shown a protective role on the disorders of glucose and lipid metabolism. However, the role and mechanism of this peptide on the hepatic glucose production has remained unclear. Adropin knockout (KO) mice were generated to explore its effects on the enhanced hepatic glucose production in obesity. We found that compared to wild-type (WT) mice, adropin-KO mice developed the unbalanced enhanced hepatic glucose production in advance of the whole-body insulin resistance (IR) by high-fat diet (HFD). Mechanistically, adropin dissociated CREB-CRTC2 and FoxO1-PGC1α complex and reduced their binding to the promoters of G6Pase and PEPCK to decrease glucose production in IR. However, these effects were not observed in insulin-sensitive hepatocytes. Furthermore, in IR hepatocytes, dampened AMPK signaling was re-activated by adropin treatment via inhibition of PP2A. To further authenticate AMPK role in vivo, we administrated HFD-fed mice with AAV8-CA AMPKα and found that AMPK activation functionally restored the aberrant glucose production and IR induced by adropin-deficiency. This study provides evidence that adropin activates the AMPK pathway via inhibition of PP2A and decreases the liver glucose production in IR context. Therefore, adropin may represent a novel target for the prevention and treatment of diabetes.

Adropin protects against liver injury in nonalcoholic steatohepatitis via the Nrf2 mediated antioxidant capacity.

Adropin, a secretory signal peptide, has shown beneficial effects on improving glucose homeostasis and dyslipidemia. However, whether this peptide affects nonalcoholic steatohepatitis (NASH) has remained unclear. In this study, the serum adropin levels, liver injury and oxidative stress were measured in diet-induced NASH mice. Adropin knock-out mice and palmitate treated primary hepatic cells were used to investigate the influence of adropin on liver injury. Our results show that serum adropin levels were decreased and negatively correlated with liver injury in NASH mice. Knockout of adropin significantly exacerbated hepatic steatosis, inflammatory responses and fibrosis in mice after either methionine-choline deficient diet (MCD) or western diet (WD) feeding. And the treatment with adropin bioactive peptides ameliorated NASH progression in mice. Adropin alleviated hepatocyte injury by upregulating the expression of Gclc, Gclm, and Gpx1 in a manner dependent on Nrf2 transcriptional activity and by increasing the glutathione (GSH) levels. And adropin significantly increased CBP expression and promoted its binding with Nrf2, which enhanced Nrf2 transcriptional activity. Furthermore, AAV8-mediated overexpression of hepatic Nrf2 expression functionally restored the liver injury induced by adropin-deficiency MCD-fed mice. These findings provide evidence that adropin activates Nrf2 signaling and plays a protective role in liver injury of NASH and therefore might represent a novel target for the prevention and treatment of NASH.

Association of sex hormone-binding globulin with nonalcoholic fatty liver disease in Chinese adults.

BACKGROUND: Sex hormone-binding globulin (SHBG), a glycoprotein synthesized by hepatocytes, has been linked to insulin resistance and hepatic lipid metabolism and is suggested to be associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the association of SHBG with NAFLD in Chinese adults. METHODS: We conducted a community-based, cross-sectional study in China involving 2912 participants aged 40-75 years old. All participants underwent detection for hepatic fat infiltration by ultrasound in addition to providing complete medical history and undergoing physical and blood biochemical examinations. The association of serum SHBG with the presence of NAFLD was reported by adjusted odds ratio after applying logistic regression models. To further explore the relationship between SHBG and NAFLD, mRNA expression of SHBG and hepatocyte nuclear factor 4-α (HNF4α), as well as intrahepatic triglycerides, were determined from the liver tissues of 32 subjects with different degrees of steatosis. RESULTS: Serum SHBG levels in patients with NAFLD (median, 43.8 nmol/L; interquartile range, 33.4-56.8 nmol/L) were significantly lower than those in non-NAFLD subjects (median, 63.4 nmol/L; interquartile range, 47.6-83.1 nmol/L). Serum SHBG levels were inversely correlated with WHR, trunk fat percentage, glucose, HOMA-IR, TG, UA and DHEAS, and were positively correlated with HDL-C levels (all p <  0.001). Logistic regression analysis indicated that serum SHBG levels were negatively associated with the presence of NAFLD in all subjects, as well as the subgroups stratified by sex, BMI and HOMA-IR (all p <  0.05). In human liver tissues, SHBG and HNF4α mRNA expression decreased along with the elevated grade of hepatic steatosis. Both SHBG and HNF4α mRNA expression levels were negatively correlated with intrahepatic triglycerides. CONCLUSIONS: These results demonstrate that SHBG levels were negatively associated with the presence of NAFLD in middle-aged and elderly Chinese adults.

Cyanidin-3-O-ß-glucoside combined with its metabolite protocatechuic acid attenuated the activation of mice hepatic stellate cells.

Previous studies indicated that cyanidin-3-O-ß-glucoside (C3G) as a classical anthocyanin exerted an anti-fibrotic effect in the liver, but its bioavailability was quite low. This study was undertaken to explore the restraining effect of C3G and its metabolite protocatechuic acid (PCA) on the activation of hepatic stellate cells (HSCs). Our data demonstrated that the treatment of a carbon tetrachloride-treated mice model with C3G inhibited liver fibrosis and HSC activation. In vitro, both C3G and PCA preserved the lipid droplets and retinol in primary HSCs, and additionally inhibited the mRNA expression of α-smooth muscle actin and collagen I, but elevated the level of matrix metalloproteinase-2 and liver X receptors. Only PCA suppressed the levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) secreted from HSCs significantly. In addition, C3G and PCA inhibited the proliferation and migration of HSCs. In conclusion, PCA mainly explained the in vivo inhibiting effect of C3G on HSC activation and liver fibrosis.

N-3 polyunsaturated fatty acids increase hepatic fibroblast growth factor 21 sensitivity via a PPAR-γ-ß-klotho pathway.

SCOPE: Fibroblast growth factor 21 (FGF21) participated in fish oil-mediated hepatic lipid-regulation and anti-inflammatory effects in high-fat diet fed-mice. However, fish oil supplementation did not significantly increase FGF21 protein levels. Whether fish oil-induced benefits in the liver are related to hepatic FGF21 sensitivity remains unclear. METHODS AND RESULTS: Male C57BL/6J mice were fed a low-fat diet (LFD), a high-fat diet (HFD) or a fish oil-supplemented high-fat diet (FOD) for 12 weeks. Fish oil improved HFD-induced hepatic steatosis and inflammation, while it exerted no obvious effect on FGF21 protein expression. FGF21 knockout studies demonstrated FGF21 participated in fish oil-induced metabolic benefits. In vivo and in vitro experiments showed n-3 PUFAs, DHA and EPA, enhanced hepatic FGF21 sensitivity by increased hepatic ß-klotho expression. PPAR-γ siRNA knockdown and PPAR-γ antagonist (GW9662) treatment blocked the effects of DHA to enhance ß-klotho expression and FGF21 sensitivity. In addition, PPAR-γ activation enhanced ß-klotho expression and FGF21 signaling response, illustrating PPAR-γ participated in DHA-regulated ß-klotho expression and FGF21 sensitivity. CONCLUSION: Our data indicate n-3 PUFAs increase hepatic FGF21 sensitivity and ß-klotho expression probably through a PPAR-γ-dependent mechanism, and may thereby exert hepatic beneficial effects on lipid metabolism.