Usefulness of collagen type IV in the detection of significant liver fibrosis in nonalcoholic fatty liver disease

Purpose Angiotensin receptor blockers (ARBs) can ameliorate metabolic syndrome (MetS)-associated dyslipidemia, hepatic steatosis, and glucose intolerance, suggesting that angiotensin receptor (AT1) over-activation contributes to impaired lipid and glucose metabolism, which is characteristic of MetS. The aim of this study was to evaluate changes in the lipid profile and proteins of fatty acid uptake, triacylglycerol (TAG) synthesis, and β-oxidation to better understand the links between AT1 overactivation and non-alcoholic fatty liver disease (NAFLD) during MetS. Methods Four groups of 25-week-old-rats were used: (1) untreated LETO, (2) untreated OLETF, (3) OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan/kg/d × 8 weeks) and (4) OLETF ± ARB (MINUS; 10 mg olmesartan/kg/d × 4 weeks, then removed until dissection). To investigate the dynamic shifts in metabolism, animals were dissected after an oral glucose challenge (fasting, 3 and 6 h post-glucose). Results Compared to OLETF, plasma total cholesterol and TAG remained unchanged in ARB. However, liver TAG was 55% lesser in ARB than OLETF, and remained lower throughout the challenge. Basal CD36 and ApoB were 28% and 29% lesser, respectively, in ARB than OLETF. PRDX6 abundance in ARB was 45% lesser than OLETF, and it negatively correlated with liver TAG in ARB. Conclusions Chronic blockade of AT1 protects the liver from TAG accumulation during glucose overload. This may be achieved by modulating NEFA uptake and increasing TAG export via ApoB. Our study highlights the contributions of AT1 signaling to impaired hepatic substrate metabolism and the detriments of a high-glucose load and its potential contribution to steatosis during MetS.

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“…COL-4 has been shown to accurately detect NAFLD with levels representing the degree of severity [ 58 , 59 ].…”

Section: Resultsmentioning

confidence: 99%

Chronic angiotensin receptor activation promotes hepatic triacylglycerol accumulation during an acute glucose challenge in obese-insulin-resistant OLETF rats

et al. 2021

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“…Additionally, this study did not investigate many factors and confounders claimed by other investigators to be associated with NAFLD incidence and NAFLD-related outcomes. For example, insulin resistance index, hyaluronic acid, cytokeratin-18 fragments, and apolipoprotein A1 were reported as predictors of NASH [ 31 , 45 , 46 , 47 , 48 ]. However, the related laboratory investigations are not practicable, as they are expensive and not commonly available in general practice.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Outcomes Associated with NAFLD, ASCVD, and All-Cause Mortality of Patients with Metabolic Syndrome

Jitrukthai

Kositamongkol

Boonchai

et al. 2022

JCM

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Metabolic syndrome (MetS) patients are at higher risk for nonalcoholic fatty liver disease (NAFLD), atherosclerotic cardiovascular diseases (ASCVD), and death. Given a lack of longitudinal data on patients with MetS in Southeast Asia, this study investigated the incidence of NAFLD and ASCVD and the all-cause mortality rate during a 10-year follow-up of Thai patients with MetS. Retrospective data were collected on 496 MetS patients with ultrasonography or transient elastography results. The patients had been followed up continuously by a university hospital between October 2011 and November 2021, and their mean age was 61.0 ± 10.9 years. Patients with secondary causes of hepatic steatosis were excluded. Cox proportional hazards regression models with time-varying covariates were adopted. During the 10-year follow-up, 17 patients (11.2%) developed NAFLD, and 27 (6.4%) developed ASCVD. The NAFLD and ASCVD incidence rates were 21.7 and 10.9 events per 1000 person years, respectively. The mortality rate was 14.2 deaths per 1000 person years. The prevalence of hypertension, dyslipidemia, ASCVD, NAFLD, advanced fibrosis, and cirrhosis at baseline was significantly higher in the nonsurvival group. The NAFLD incidence and mortality rate of patients with MetS were lower than those in previous studies. Intensive, holistic, and continuous care should be considered for better outcomes.

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“…Enzyme‐linked immunosorbent assay–based immunoassays were developed to detect the COL4‐7S, ( 8 ) and these have been used to study fibrogenic activity both in animal models ( 8 ) and in patients. ( 9,10 )…”

Section: Figmentioning

confidence: 99%

Editorial: Noninvasive Fibrosis Biomarkers in Patients With NASH With Diabetes

Fan

Török

2021

Hepatol Commun

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Usefulness of collagen type IV in the detection of significant liver fibrosis in nonalcoholic fatty liver disease

Cited by 23 publications

References 36 publications

Chronic angiotensin receptor activation promotes hepatic triacylglycerol accumulation during an acute glucose challenge in obese-insulin-resistant OLETF rats

Chronic angiotensin receptor activation promotes hepatic triacylglycerol accumulation during an acute glucose challenge in obese-insulin-resistant OLETF rats

Long-Term Outcomes Associated with NAFLD, ASCVD, and All-Cause Mortality of Patients with Metabolic Syndrome

Editorial: Noninvasive Fibrosis Biomarkers in Patients With NASH With Diabetes

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