Cytokine modulation by etanercept ameliorates metabolic syndrome and its related complications induced in rats administered a high-fat high-fructose diet

• Published in: Scientific reports 2022-11, Vol.12 (1), p.20227-14, Article 20227
• Main Authors: Hassan, Noha F., Hassan, Azza H., El-Ansary, Mona R.
• Format: Article
• Language: English
• Subjects: 631/45; 692/4020/1503; Adiponectin; Animals; Blood pressure; Body weight; Body weight gain; Cytokines; Diabetes mellitus; Diabetes Mellitus, Type 2; Diet, High-Fat; Dyslipidemia; Dyslipidemias; Etanercept; Etanercept - pharmacology; Etanercept - therapeutic use; Fructose; Glucose metabolism; High fat diet; Humanities and Social Sciences; Hypertension; Inflammation; Insulin; Insulin Resistance; Leptin; Metabolic disorders; Metabolic syndrome; Metabolic Syndrome - drug therapy; Monoclonal antibodies; multidisciplinary; Non-alcoholic Fatty Liver Disease - metabolism; Rats; Science; Science (multidisciplinary); TLR4 protein; Toll-like receptors; Transforming growth factor-b; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-24593-9

The aim of the present study was to investigate the effect of etanercept (ETA)—an anti-tumor necrosis factor α (TNF-α) monoclonal antibody—on metabolic disorders such as obesity, hypertension, dyslipidemia, and insulin resistance associated with the metabolic syndrome (MS). MS was induced in rats via high-fat high-fructose (HFHF) administration for 8 weeks. Rats were divided into three groups: negative control, HFHF model, and ETA-treated groups [HFHF + ETA (0.8 mg/kg/twice weekly, subcutaneously) administered in the last 4 weeks]. ETA effectively diminished the prominent features of MS via a significant reduction in the percent body weight gain along with the modulation of adipokine levels, resulting in a significant elevation of serum adiponectin consistent with TNF-α and serum leptin level normalization. Moreover, ETA enhanced dyslipidemia and the elevated blood pressure. ETA managed the prominent features of MS and its associated complications via the downregulation of the hepatic inflammatory pathway that induces nonalcoholic steatohepatitis (NASH)—from the expression of Toll-like receptor 4, nuclear factor kappa B, and TNF-α until that of transforming growth factor—in addition to significant improvements in glucose utilization, insulin sensitivity, and liver function parameter activity and histopathological examination. ETA was effective for the treatment of all prominent features of MS and its associated complications, such as type II diabetes mellitus and NASH.