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Obesity is an expanding global public health problem and a leading cause of metabolic disorders. The hepatokine Fetuin B participates in regulating insulin resistance, glucose metabolism and liver steatosis. However, the mechanism underlying Fetuin B activation remains unclear. Our previous population-based study demonstrated a significant association between serum Fetuin B and body fat mass in an obese population, which indicates its potential in mediating obesity-related metabolic disorders. In the present study, we further revealed a significant correlation between Fetuin B and leptin, the classic adipokine released by expanding adipose tissue, in this obese population. Consistently, elevated Fetuin B and leptin levels were confirmed in diet-induced obese mice. Furthermore, an in vitro study demonstrated that the leptin signalling pathway directly activated the transcription and expression of Fetuin B in primary hepatocytes and AML12 cells in a STAT3-dependent manner. STAT3 binds to the response elements on FetuB promoter to directly activate FetuB transcription. Finally, the mediating effect of Fetuin B in insulin resistance induced by leptin was confirmed according to mediation analysis in this obese population. Therefore, our study identifies leptin-STAT3 as an upstream signalling pathway that activates Fetuin B and provides new insights into the pathogenic mechanisms of obesity-related metabolic disorders. [ABSTRACT FROM AUTHOR]

Our aim was to assess effects of breast-feeding (BF) in the association between large-for-gestational age (LGA) and body mass index (BMI) trajectories on childhood overweight from 1 to 4 years old. A total of 1649 healthcare records of mother–child pairs had detailed records of feeding practices and were included in this retrospective cohort study. Data were available in Medical Birth Registry of Xiamen between January 2011 and March 2018. Linear and logistic regression models were used to access the difference between BF and no-BF group. For offspring were LGA and BF was significantly associated with a lower BMI Z-score from 1 to 4 years old after adjustment confounders in Model 1 to 3 [difference in BMI Z-score in Model 1: estimated β: −0.07 [95%CI: −0.13 to −0.01]; Model 2: estimated β: −0.07 (−0.13 to −0.004); Model 3: estimated β: −0.06 (−0.12 to −0.001); P = 0.0221, 0.0371, 0.0471]. A significantly lower risk of childhood overweight was observed in Model 1 [odd ratio (OR): 0.85 (95%CI, 0.73 to 1.00)], P = 0.0475) with adjustment for maternal pre-pregnancy BMI. Furthermore, Model 2 and Model 3 showed LGA-BF infants had a lower risk for childhood overweight then LGA-no-BF infants [OR: 0.87 and 0.87 (95%CI, 0.73 to 1.03; 0.74 to 1.03)], however, there was no statistical significance (P = 0.1099, and 0.1125)]. BF is inversely related to BMI Z-score and risk for overweight in children were LGA from 1 to 4 years old. Adjustment for maternal pre-pregnancy BMI, the protective association between BF and childhood overweight was more significant. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease is likely to be associated with increased circulating branched-chain amino acids. We investigated the relationship between changes in branched-chain amino acids levels in the serum and improvement in liver fat content caused by exercise intervention in individuals with nonalcoholic fatty liver disease. The exploratory study included 208 central obesity and nonalcoholic fatty liver disease individuals from an exercise intervention randomized clinical trial for nonalcoholic fatty liver disease. The participants were randomly assigned to control, moderate, and vigorous-moderate exercise groups for 12 months. Changes in total branched-chain amino acids, leucine, isoleucine, and valine levels from baseline to 6 months were calculated. Liver fat content was determined by proton magnetic resonance spectroscopy. Reductions in circulating levels of total branched-chain amino acids, leucine, and valine levels from baseline to 6 months were significantly associated with the improvement of liver fat content at 6 months and 12 months (p < 0.01 for all) after adjustments for age, sex, total energy intake, protein intake, intervention groups, HOMA-IR, BMI, liver fat content, total branched-chain amino acids, leucine, and valine at baseline, respectively. These associations were still significant after further adjustments for changes in HOMA-IR and BMI from baseline to 6 months (p < 0.05 for all). Our findings indicated that reductions in circulating branched-chain amino acids levels were associated with an improvement in liver fat content by exercise intervention among patients with nonalcoholic fatty liver disease, which was independent of changes in BMI or HOMA-IR. [ABSTRACT FROM AUTHOR]

The present study aimed to explore the independent association and potential pathways between serum uric acid (SUA) and nonalcoholic fatty liver disease (NAFLD). 1365 community-living obese Chinese adults who received hepatic ultrasonography scanning were included. The prevalence rates of NAFLD were 71.5% for men and 53.8% for women. Compared with controls, NAFLD subjects showed significantly increased SUA levels (333.3 ± 84.9 v.s. 383.4 ± 93.7 μmol/L) and prevalence rate of hyperuricemia (HUA) (25.7% v.s. 47.3%, p < 0.001). After adjustment for insulin resistance (IR), components of metabolic syndrome (MetS) and other potential confounders, elevated SUA is independently associated with increased risk of NAFLD, with the adjusted OR of 1.528-2.031 (p < 0.001). By using multivariable fractional polynomial (MFP) modeling, the best FP transformation model shows that SUA was independently and linearly associated with risk of NAFLD. The one-pathway model by using structural equation modeling (SEM) about the relationships among SUA, IR, components of metabolic syndrome and NAFLD fits well (χ2 = 57.367, p < 0.001; CFI = 0.998; TLI = 0.992; and RMSEA = 0.048) and shows SUA might increase the risk of NAFLD directly besides of the indirect effects through increasing fasting insulin, blood pressure, triglyceride and decreasing HDL-C levels. Our results imply that elevated SUA may play an important role in NAFLD pathogenesis. [ABSTRACT FROM AUTHOR]