Effects of phosphorus and fenofibrate on lipid deposition, mitochondrial function and protein synthesis in obscure puffer (Takifugu obscurus)

Abstract

This study aimed to investigate the effects of phosphorus (P) restriction and fenofibrate (F) on lipid deposition, mitochondrial function and protein synthesis in obscure puffer using in vivo and in vitro studies. In vivo, healthy fish with an initial body weight of 18.21 ± 0.04 g were fed three diets supplemented with different P and fenofibrate contents for 10 weeks: Control (5.3 g/kg P), P0 (0 g/kg P) and P0 + F (0 g/kg P and 3.5 g/kg F). The results indicated that P0 treatment significantly reduced weight gain rate and protein deposition, but increased body lipid accumulation, hepatic lipid droplets and serum triglyceride and cholesterol content (P < 0.05). However, P0 + F treatment reversed these. Furthermore, P0 treatment was found to inhibit the mRNA levels of pparα, lpl and cyp7a1, whereas P0 + F treatment significantly increased the expression levels of these genes. In vitro, primary hepatocytes were cultured for 48 h in three different culture media: Control (normal DMEM medium), P0 (DMEM without P), and P0 + F (DMEM without P + 200 mM F). The results showed that P0 significantly decreased the mRNA and protein expression levels of Pparα (P < 0.05), and P0 + F up-regulated mRNA expression levels of pparα compared with P0 group (P < 0.05). Furthermore, P0 inhibited the expression levels of genes associated with fatty acid β-oxidation (cpt1 and acox1) and transport (cd36), but elevated the expression levels of genes related to lipid synthesis (fas, me, g6pd and dgat1) and cholesterol synthesis (hmgcr) (P < 0.05). However, P0 + F reversed these effects. P0 decreased mitochondrial abundance, membrane potential and ATP content, increased the mRNA expression level of ampk and 4epb1 and inhibited the mRNA expression of pgc1-α and the protein expression of mTOR and S6k (P < 0.05), whereas P0 + F increased mitochondrial abundance and membrane potential, increased mtor mRNA expression and inhibited 4ebp1 mRNA expression. Overall, this study suggests that P deficiency leads to lipid and cholesterol accumulation and impaired growth in fish, and fenofibrate can alleviate these effects by improving lipid and cholesterol metabolism, mitochondrial function, and protein synthesis.