Structurally-Engineered Fatty Acid 1024 (SEFA-1024) Treats Non-Alcoholic Fatty Liver Disease
Jordan Secor1,2, Bennet Cho1,2, Lumeng Jenny Yu1,2, Amy Pan1,2, Victoria Ko1,2, Mark Puder1,2
1Boston Children’s Hospital Vascular Biology Program, Boston, MA, 2Boston Children's Hospital Department of Surgery, Boston, MA
Background: Therapies are needed to treat the 24% of Americans with non-alcoholic fatty liver disease (NAFLD) and help mitigate the shortage of liver transplant donors relative to recipients. SEFA-1024 is a fully-synthetic long chain fatty acid designed to maximize fatty acid signaling potency through avoiding rapid metabolism. Here, we investigate the efficacy of SEFA-1024 in treating diet-induced obesity, steatohepatitis, and insulin resistance in a murine NAFLD model.
Methods: C57BL/6 mice were fed chow (10% fat) or high fat diet (HFD, 60% fat) for 15 weeks. Subsequently, the HFD group were treated via orogastric gavage with SEFA-1024 or MCT as a vehicle control. After 5 weeks of treatment, all mice underwent oral glucose tolerance testing (GTT). One week later, body masses, serum AST and ALT, and liver histology were analyzed.
Results: SEFA-1024 reversed obesity caused by HFD (A). On GTT, SEFA-1024 inhibited HFD-induced hyperglycemia (B) and hyperinsulinemia (C). Liver H&E staining (D-F) demonstrated HFD-mediated hepatic steatosis (E, arrows) which was treated by SEFA-1024 (F). Serum AST and ALT were significantly elevated by HFD but not when treated with SEFA-1024 (G&H).
Conclusion: SEFA-1024 reduces HFD-induced obesity, hepatic steatosis, inflammation, hyperglycemia, and hyperinsulinemia in a murine model of chronic, diet-induced liver injury. SEFA-1024 demonstrates the potential to mitigate the deleterious effects of metabolic syndrome in obese patients which could reduce the prevalence of NAFLD and need for liver transplantation.
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