Critical role of triglycerides for adiponectin levels in hepatitis C: a joint study of human and HCV core transgenic mice

Abstract

Abstract Background Both hepatitis C virus (HCV) infection and adiponectin are critically involved in metabolism. The reversal and associations of altering adiponectin levels after sustained virological responses (SVRs) following direct-acting antivirals (DAA) in HCV-infected patients remained elusive. Methods A joint study was conducted in a prospective cohort of 427 HCV-infected patients and a line of HCV core transgenic mice. Results Of 427, 358 had completed a course of DAA therapy and 353 had SVRs. At baseline, male sex (95% CI β: − 1.44 to − 0.417), estimated glomerular filtration rate (eGFR) (− 0.025 to − 0.008), triglycerides (− 0.015 to − 0.005), and fibrosis-4 levels (0.08–0.297) were associated with adiponectin levels; BMI (0.029–0.327) and triglycerides levels (0.01–0.03) were associated with homeostatic model assessment for insulin resistance (HOMA-IR) in HCV-infected patients. At 24-week post-therapy, in SVR patients, male sex (− 1.89 to − 0.5) and eGFR (− 0.02 to − 0.001) levels were associated with adiponectin levels, levels of BMI (0.094–0.335) and alanine transaminase (0.018–0.078) were associated with HOMA-IR; compared with baseline levels, adiponectin levels decreased (6.53 ± 2.77 vs. 5.45 ± 2.56 μg/mL, p < 0.001). In 12-month-old HCV core transgenic mice with hepatic steatosis, triglyceride levels (0.021–0.111) were associated with adiponectin levels, and hepatic adipopnectin expression was comparable with that of control mice. Conclusions Triglycerides and hepatic fibrosis are associated with HCV-specific alteration of adiponectin levels, and adiponectin may affect insulin sensitivity through triglycerides during HCV infection. In DAA-treated patients, after SVR, adiponectin levels decreased and the linking function of triglycerides between adiponectin and insulin sensitivity vanished. Moreover, HCV core with hepatic steatosis might affect extrahepatic adiponectin expression through triglycerides.