Su1795 Uric Acid Regulates Hepatic Steatosis and Insulin Resistance Through the NLRP3 Inflammasome Dependent Mechanism

IntroductionSystemic chronic low-grade inflammation has been linked to insulin resistance (IR) and non-alcoholic steatohepatitis (NASH). NOD-like receptor protein 3 (NLRP3) inflammasome and its final product, interleukin (IL)-1β, exert detrimental effects on insulin sensitivity and promote liver inflammation in murine models. Evidence linking hepatic NLRP3 inflammasome, systemic IR and NASH has been scarcely explored in humans. Herein, we correlated the hepatic abundance of NLRP3 inflammasome components and IR and NASH in humans.Research design and methodsMetabolically healthy (MH) (n=11) and metabolically unhealthy (MUH) (metabolic syndrome, n=21, and type 2 diabetes, n=14) subjects were recruited. Insulin sensitivity (homeostatic model assessment of IR (HOMA-IR) and Oral Glucose Sensitivity (OGIS120)), glycemic (glycated hemoglobin), and lipid parameters were determined by standard methods. Plasma cytokines were quantified by Magpix. Hepatic NLRP3 inflammasome components were determined at the mRNA and protein levels by reverse transcription–quantitative PCR and western blot, respectively. Liver damage was assessed by histological analysis (Non-alcoholic Fatty Liver Disease Activity Score (NAS) and Steatosis, Inflammatory Activity, and Fibrosis (SAF) scores). IR and liver histopathology were correlated with NLRP3 inflammasome components as well as with liver and plasma IL-1β levels.ResultsBody Mass Index, waist circumference, and arterial hypertension frequency were significantly higher in MUH subjects. These patients also had increased high-sensitivity C reactive protein levels compared with MH subjects. No differences in the plasma levels of IL-1β nor the hepatic content of Nlrp3, apoptosis-associated speck-like (Asc), Caspase-1, and IL-1β were detected between MUH and MH individuals. MUH subjects had significantly higher NAS and SAF scores, indicating more severe liver damage. However, histological severity did not correlate with the hepatic content of NLRP3 inflammasome components nor IL-1β levels.ConclusionOur results suggest that NLRP3 inflammasome activation is linked neither to IR nor to the inflammatory status of the liver in MUH patients.

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The application value of serum 25(OH)D3, uric acid, triglyceride, and homeostasis model assessment of insulin resistance in male patients with hyperuricemia combined with hypogonadism

BMC Endocrine Disorders ◽

10.1186/s12902-021-00765-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Qun Zhang ◽

Wei Chen ◽

Canqin Yun ◽

Juan Wang

Keyword(s):

Insulin Resistance ◽

Logistic Regression ◽

Uric Acid ◽

Free Testosterone ◽

Normal Group ◽

Model Assessment ◽

Homeostasis Model Assessment ◽

Alcoholic Fatty Liver ◽

Male Patients ◽

Function Group

Abstract Background The purpose of this study was to investigate the application value of serum 25(OH)D3, uric acid, triglyceride (TG), and homeostasis model assessment of insulin resistance (HOMA-IR) in male patients with hyperuricemia combined with hypogonadism. Methods From August 2018 to August 2020, a total of 198 male patients with primary hyperuricemia were prospectively enrolled in our hospital for inpatient treatment in the department of Metabolism and Endocrinology. They are divided into normal gonadal function group (normal group, n = 117) and hypogonadal function group (hypogonadism group, n = 81), according to free testosterone (FT) level, International Index of Erectile Function (IIEF-5), and androgen deficiency in the aging male (ADAM) questionnaires. Laboratory indexes were compared between two groups. Multivariate logistic regression was applied to analyze the influencing factors of hypogonadism. Results Among the 198 hyperuricemia patients, 40.91 % were hypogonadism. Compared with the normal group, the BMI, waist circumference (WC), and the prevalence of non-alcoholic fatty liver disease (NAFLD), hyperlipidemia (HLP), and obesity (OB) in the hypogonadism group were higher, and the difference was statistically significant (P < 0.05, respectively). The levels of fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), triacylglycerol (TG), serum uric acid (SUA), alanine transaminase (ALT) of hypogonadism group were higher than those of normal group, while the levels of TT, FT, E2, 25(OH)D3 of hypogonadism group were lower than those of normal group (P < 0.05, respectively). Pearson’s linear correlation was used to analyze the correlation between the indicators with significant differences in general data and laboratory indicators and hypogonadism. BMI, WC, HOMA-IR, TG, SUA, TT, FT, 25(OH)D3, E2 were positively correlated with hypogonadism (r = 0.556, 0.139, 0.473, 0.143, 0.134, 0.462, 0.419, 0.572, 0.601, P = 0.012, 0.027, 0.018, 0.019, 0.028, 0.029, 0.030, 0.009, 0.003, respectively). Taking the above indicators as independent variables and hypogonadism as the dependent variable, logistic regression analysis found that the risk factors for hypogonadism were SUA, WC, BMI, HOMA-IR, TG, TT, FT, E2, and 25(OH) D3. Conclusions Serum 25(OH)D3, SUA, HOMA-IR, TG levels were positively correlated with male hyperuricemia patients with hypogonadism. They have important application value in the diagnosis of male hyperuricemia patients with hypogonadism.

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