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Serum Adropin as a Potential Biomarker for Predicting the Development of Type 2 Diabetes Mellitus in Individuals With Metabolic Dysfunction-Associated Fatty Liver Disease.

ABSTRACT: Background: Adropin, a peptide translated from the Energy Homeostasis Associated gene (ENHO), was mainly expressed in the liver and was a regulator in metabolic and energy homeostasis. This study aims to investigate the correlation between adropin and histological characteristics of the liver, and the clinical relevance of adropin in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: A total of 62 subjects, including 32 healthy controls and 30 MAFLD patients, were enrolled in this case-control study. The MAFLD patients were further divided into two subgroups, including NGT-M group and T2DM-M group. Serum adropin levels, metabolic parameters and intrahepatic lipids, the liver ENHO mRNA expressions and histological characteristics were investigated. Results: MAFLD patients showed significantly lower circulating adropin compared with healthy controls (2.02 ± 2.92 vs. 5.52 ± 0.65 ng/mL, P < 0.0001). Subgroup analysis exhibited dramatically declined serum adropin levels in T2DM-M patients compared with NGT-M group (0.51 ± 0.73 vs. 4.00 ± 3.52 ng/mL, P < 0.001). H&E and Oil Red O staining show exacerbated steatohepatitis in T2DM-M patients in contrast with NGT-M group. Furthermore, serum adropin concentrations were negatively correlated with intrahepatic triglyceride (TG), total cholesterol (TC), and NAFLD activity score (NAS) (TG: r = -0.495; TC: r = -0.392; NAS: r = -0.451; all P < 0.05). Conclusions: MAFLD patients showed significantly lower adropin levels than the healthy controls, especially in T2DM patients. Adropin maybe a potential biomarker for predicting the development of MAFLD, especially in T2DM individuals.

SUBMITTER: Li N

PROVIDER: S-EPMC8339918 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Aims/introductionMetabolic dysfunction-associated fatty liver disease (MAFLD), defined as hepatosteatosis with type 2 diabetes mellitus, overweight/obesity or metabolic dysregulation, has been proposed as a new feature of chronic liver disease. Fatty acid-binding protein 4 (FABP4) is expressed in adipose tissue, and secreted FABP4 is associated with the development of insulin resistance and atherosclerosis. However, the relationship between MAFLD and FABP4 has not been fully addressed.Materials and methodsAssociations of MAFLD with metabolic markers, including FABP4, fibroblast growth factor 21 and adiponectin, were investigated in 627 individuals (men/women 292/335) in the Tanno-Sobetsu Study, a population-based cohort.ResultsThe mean age was 65 years (range 19-98 years, median [interquartile range] 68 [56-76] years). Hepatosteatosis was determined by the fatty liver index (FLI), and FLI ≥35 for men and FLI ≥16 for women were used for detection of fatty liver, as previously reported using 14,471 Japanese individuals. FLI was positively correlated with systolic blood pressure and levels of FABP4 (r = 0.331, P < 0.001), fibroblast growth factor 21, homeostasis model assessment of insulin resistance as an insulin resistance index and uric acid, and was negatively correlated with levels of high-density lipoprotein cholesterol and adiponectin. FABP4 concentration was independently associated with FLI after adjustment of age, sex, systolic blood pressure and levels of uric acid, high-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance, adiponectin and fibroblast growth factor 21 in multivariable regression analysis. Logistic regression analysis showed that FABP4 was an independent predictor of MAFLD after adjustment of age, sex, presence of diabetes mellitus, hypertension and dyslipidemia, and levels of uric acid, homeostasis model assessment of insulin resistance, adiponectin and fibroblast growth factor 21.ConclusionsFABP4 concentration is independently associated with FLI and is an independent predictor of MAFLD in middle-aged and elderly individuals.

Project description:BackgroundIn 2020, an international expert panel proposed a new definition of fatty liver: Metabolic dysfunction-associated fatty liver disease (MAFLD). The MAFLD added the criteria for defining metabolic dysfunctions, which are high-risk factors for liver-related and cardiovascular events. Contrary to the non-alcoholic fatty liver disease (NAFLD) definition, it allows the coexistence of MAFLD and significant alcohol use in the same patient.AimTo review the existing data that evaluate the clinical profile and long-term outcome difference between the patients identified as MAFLD and NAFLD.MethodsDatabases MEDLINE via PubMed and EMBASE were searched and relevant publications up to June 28, 2022 were assessed. Studies were included if they involved human participants diagnosed with MAFLD.ResultsA total of 2324 records were reviewed, of which 1575 duplicate citations were removed. Of the 2324 records screened, 207 articles were excluded, and 542 articles were assessed for their eligibility, for which 511 were excluded. The remaining 31 articles were selected for review. MAFLD diagnostic criteria were able to identify more individuals with fatty liver. Studies have shown that patients included using the MAFLD criteria were associated with higher risks of hepatic fibrosis when compared to NAFLD. All-cause mortality, cardiovascular disease-related, and cancer-related mortality were shown to be higher in MAFLD patients. MAFLD patients also had higher baseline metabolic derangement, and risks of developing obesity, diabetes, and cardiovascular events. Of the 3 subtypes, diabetes mellitus has the strongest association with negative outcomes, followed by metabolic dysfunction and elevated body mass index. Within the subtypes of MAFLD, patients with more metabolic conditions at the time of diagnosis had worse hepatic and liver injury compared to those with a single metabolic condition.ConclusionMAFLD is a new definition of fatty liver disease that is gaining increasing acceptance. It is based on empirical clinical practice on positive inclusion of metabolic risk factors and recent evidence suggests that it helps to identify patients with higher risk for liver-related as well as cardiovascular events.

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Serum Adropin as a Potential Biomarker for Predicting the Development of Type 2 Diabetes Mellitus in Individuals With Metabolic Dysfunction-Associated Fatty Liver Disease.

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