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Background: To reveal the role of branched-chain amino acids (BCAAs) in the development and progression of nonalcoholic fatty liver disease (NAFLD) and the effect on the incidence of subsequent cardiovascular disease., Methods: A total of 1302 subjects in the cohort study of the Huai'an Diabetes Prevention Program were divided into two groups according to whether NAFLD was present at baseline. The group without NAFLD at baseline was only followed up, and the group with NAFLD at baseline received diet and exercise interventions. Anthropometric and biochemical examinations were performed at baseline and at the end of 4 years for all subjects. Serum BCAA (leucine, isoleucine, and valine) levels were measured by hydrophilic interaction chromatography-tandem mass spectrometry. The associations of baseline serum BCAA levels with the risk for NAFLD, coronary heart disease (CHD), and cardiovascular events (CVEs) after 4 years were further evaluated., Results: (1) At baseline and after the 4-year follow-up, baseline serum leucine, valine, and total BCAAs in the NAFLD group were significantly higher than those in the non-NAFLD group (p < 0.05). (2) According to whether NAFLD was present at baseline and after follow-up, all subjects were divided into four groups, including the control group, new case group, improvement group, and unchanged group. There was no significant difference in baseline BCAAs levels between the new case group and the improvement group (p > 0.05). (3) Risk factors for the occurrence and development of NAFLD were analysed by a multiple logistic regression model according to whether NAFLD existed at baseline. Serum leucine (OR = 1.058, 95% CI 1.005-1.114, p = 0.033) and total BCAAs (OR = 1.023, 95% CI 1.001-1.046, p = 0.045) were independent risk factors for new-onset NAFLD. Serum valine (OR = 1.131, 95% CI 1.043-1.226, p = 0.003), and total BCAAs (OR = 1.040, 95% CI 1.003-1.078, p = 0.035) were independent risk factors showing that NAFLD could not be reversed. (4) The cross-table Chi-square test showed that the incidence of both CHD and CVEs was significantly highest in the new case group (p < 0.05). (5) After adjusting for confounding factors, baseline isoleucine, valine, and BCAA levels were independently associated with new-onset CHD in subjects with or without NAFLD at baseline (p < 0.05)., Conclusions: High BCAA levels exacerbate the risk of CHD and CVEs by influencing the occurrence and progression of NAFLD. However, lifestyle interventions could reverse the risk of NAFLD, CHD and CVEs associated with BCAAs., (© 2022. Asian Pacific Association for the Study of the Liver.)

Objective: This study aimed to investigate the association of serum betatrophin with the status and progression of nonalcoholic fatty liver disease (NAFLD)., Methods: A total of 249 subjects who received ultrasonic examination of liver fat content (LFC) were recruited. Anthropometric and biochemical examinations were performed. Serum betatrophin was measured by ELISA., Results: Compared with control group, serum betatrophin significantly increased in NAFLD group (P < 0.05). There was significant difference in serum betatrophin among control, low liver fat content (LLFC), and high liver fat content (HLFC) groups (P < 0.01). After adjustment for gender, age, BMI, FPG and HbA1c, the betatrophin positively correlated with LFC (r = 0.185, P < 0.01) and TG (r = 0.195, P < 0.01). Stepwise multiple regression analysis indicated serum betatrophin was independently related to LFC (P < 0.05). Multivariate logistic regression analysis revealed subjects in the highest tertile of serum betatrophin had higher odds of having NAFLD after adjustment for traditional NAFLD risk factors (OR = 2.88, 95%CI: 1.15-7.19) (P<0.05)., Conclusion: Serum betatrophin is an independent risk factor for NAFLD and potential non-invasive marker for its progression. Serum betatrophin may be helpful for the early diagnosis of NAFLD and improvement of its prognosis., Competing Interests: The authors have declared that no competing interests exist.

This study aimed to investigate the effects of PPM1K rs1440581 and rs7678928 single nucleotide polymorphisms (SNPs) on the serum branched-chain amino acids (BCAAs) levels and cardiovascular disease (CVD) risk. Anthropometric and biochemical examinations were performed at baseline and the end of 4 years in 234 individuals who were randomly recruited from the Diabetes Prevention Programme in Huai'an and received lifestyle intervention and follow up for 4 years. Serum BCAAs (leucine, isoleucine and valine (Val)) levels were measured by hydrophilic interaction chromatography-tandem mass spectrometric method and the PPM1K rs1440581 and rs7678928 were detected by high-throughput SNP genotyping at baseline. The associations of rs1440581 and rs7678928 with serum BCAA levels and risk for CVD after 4 years were further evaluated. The distribution frequencies of PPM1K rs1440581 and rs7678928 met the Hardy-Weinberg equilibrium (p>.05). The baseline serum levels of Val (p =.022) and total BCAAs (p =.026) in subjects with rs1440581 CC genotype were higher than in those with TT genotype. There were no significant differences in the serum levels of BCAAs among subjects with different genotypes of rs7678928. After 4-year follow-up, the subjects with rs1440581 CC genotype had higher systolic blood pressure (SBP) (p =.027), diastolic blood pressure (DBP) (p =.019), triglycerides (TGs) (p =.019) and lower high-density lipoprotein cholesterol (HDL-c) (p =.008) than those with TT genotype, and had higher AST level than those with TT (p =.030) or TC (p =.003) genotype; the subjects with rs7678928 TT genotype had higher SBP (p =.039) and DBP (p =.019) and lower HDL-c than those with CC (p =.017) genotype. Lifestyle intervention had little influence on the serum levels of fasting plasma glucose (FPG), TG, HDL-c, alanine aminotransferase (ALT), AST and creatinine (CREA) in subjects with rs1440581 CC genotype or rs7678928 TT genotype (p>.05). The incidences of CVD and non-alcoholic fatty liver disease (NAFLD) in subjects with rs1440581 CC genotype were higher than in those with TT genotype; the incidence of CVD in subjects with rs7678928 TT genotype was higher than in those with CC (p <.05) genotype. Allele C of PPM1K rs1440581 was associated with elevated serum Val, total BCAAs and CVD risks. rs1440581 CC genotype may be a better marker than baseline serum BCAAs in predicting the risk for CVD. Diabetes Prevention Programme in Huai'an of Huai'an Second People's Hospital, ChiCTR-TRC-14005029. Allele C of PPM1K rs1440581 was relevant to elevated serum Val and total BCAAs. PPM1K rs1440581 CC and rs7678928 TT genotypes were associated with CVD risk. PPM1K rs1440581 CC genotype carriers were more likely to have liver injury and develop NAFLD. [ABSTRACT FROM AUTHOR]