Effects of astaxanthin on the mechanisms involved in skeletal muscle lipid metabolism and oxidative stress in an experimental model of metabolic syndrome

This study aimed to evaluate the mechanisms involved in skeletal muscle lipotoxicity, impaired lipid metabolism, and oxidative stress induced by a sucrose-rich diet (SRD) that mimics human Metabolic Syndrome (MS), and to assess the preventive effects and molecular mechanisms of astaxanthin (AXT) extracted from freshwater crabs (<i>Dilocarcinus pagei</i>) on these alterations. Male Wistar rats received a reference diet (RD), RD + AXT, SRD, or SRD + AXT (10 mg kg^-1 day^-1 orally) for 90 days. Serum glucose, triglycerides, and cholesterol were measured. In skeletal muscle, triglyceride content, activities of lipogenic enzymes [fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), malic enzyme (ME), glucose-6-phosphate dehydrogenase (G-6-PDH)] and mitochondrial β-oxidation enzyme [carnitine palmitoyltransferase-1 (CPT-1)] were assessed, along with the expression of transcription factors sterol regulatory element binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptor-α (PPARα) by qPCR. Oxidative stress was evaluated by reactive oxygen species (ROS), glutathione (GSH), and antioxidant enzymes (CAT, GPx, GR), as well as pNFκB p65 and NrF2 protein levels. SRD feeding induced dyslipidemia, intramuscular triglyceride accumulation, increased <i>de novo</i> lipogenesis and SREBP-1c expression, and reduced CPT-1 activity and PPARα expression in skeletal muscle. Oxidative stress was evidenced by elevated ROS and decreased GSH and antioxidant enzyme activities, with reduced NrF2 and increased pNFκB p65 levels. AXT supplementation attenuated these alterations by downregulating lipogenic enzymes and SREBP-1c, enhancing CPT-1 and PPARα expression, and modulating NrF2 and pNFκB p65, thus improving lipid metabolism and redox balance in skeletal muscle. This study revealed new aspects of skeletal muscle lipid accumulation, lipid metabolism, and oxidative stress in SRD-fed rats. We demonstrated the novel properties and molecular mechanisms of AXT extracted from freshwater crabs on these parameters in the skeletal muscle of an experimental model of MS.