Furan fatty acids supplementation in obese mice reverses hepatic steatosis and protects against cartilage degradation

Abstract

Obesity is a major global health problem associated with numerous metabolic dysfunctions, an increased risk of developing Metabolic Associated Steatotic Liver Disease (MASLD) and osteoarthritis. Recently, we demonstrated that in Diet-induced-Obesity (DIO) mouse model, preventive furan fatty acids (FuFA-F2) supplementation, a natural compounds found in many foods, reduced the onset of metabolic disorders and increased muscle mass. Here, we aimed to determine whether a short FuFA-F2 supplementation is capable of providing beneficial health effects in obese mice, notably by reversing metabolic disorders and limiting cartilage degradation. 6-month-old obese C57Bl/6 J mice were fed for four additional weeks on a high-fat and high-sucrose (HFHS) diet, supplemented or not with FuFA-F2 (40 mg/day/kg of body weight). Liver triglyceride content and histologic analysis revealed that 4 weeks of FuFA-F2 supplementation fully reversed hepatic steatosis in obese mice. Liver RNA-sequencing analysis highlighted that FuFA-F2 partly reversed the gene expression signature induced by the HFHS diet and favorably changed the expression of many genes known to be involved in the development of hepatic steatosis such as Pcsk9, Stard4, Insig1 and Sulf2. We also found that FuFA-F2 supplementation increased skeletal muscle mass and protected against cartilage degradation and synovitis induced by obesity. Our findings demonstrated that FuFA-F2 supplementation for 4 weeks in obese mice was enough to reverse the development of MASLD, promote an increase in skeletal muscle mass and protect against cartilage degradation induced by the HFHS diet. This study highlights that nutritional supplementation with FuFA-F2 could be an effective approach to treat obesity-related disorders.

Keywords: Furan fatty acids; Liver steatosis; Obesity; Osteoarthritis; RNA-sequencing; Skeletal muscle.