Impaired peroxisomal fat oxidation induces hepatic lipid accumulation and oxidative damage in Nile tilapia.

Many metabolic diseases in fish are often associated with lowered peroxisomal fatty acid (FA) ß-oxidation. However, the physiological role of peroxisomal FA oxidation in lipid metabolism in fish still remains unclear. In the present study, a specific peroxisomal FA ß-oxidation inhibitor, 10,12-tricosadiynoic acid (TDYA), was used to investigate the effects of impaired peroxisomal ß-oxidation on growth performance, health status, and lipid metabolism in Nile tilapia. The results showed that the dietary TDYA treatment did not affect weight gain, but significantly decreased peroxisomal ß-oxidation in the liver, and increased body fat accumulation. The fish with impaired peroxisomal ß-oxidation exhibited higher contents of serum lipid and peroxidation products, and alanine aminotransferase activity, and significantly lowered hepatic activities of superoxide dismutase and catalase. The inhibited peroxisomal ß-oxidation did not enhance mitochondrial ß-oxidation activity, but compensatorily upregulated FA ß-oxidation-related gene expression, and downregulated the gene expressions in lipolysis and lipogenesis. Taken together, TDYA treatment markedly induced lipid accumulation and hepatic oxidative damage via systemically depressing lipid catabolism and antioxidant capacity. Our findings reveal the pivotal roles of peroxisomal ß-oxidation in maintaining health and lipid homeostasis in fish, and could be helpful in understanding metabolic diseases in fish.

Inhibition of intestinal lipases alleviates the adverse effects caused by high-fat diet in Nile tilapia.

Intestinal lipases are fat-digesting enzymes, which play vital roles in lipid absorption in the intestine. To study the regulation of intestinal lipase activity in systemic lipid metabolism in fish, especially in the metabolic diseases caused by high-fat diet (HFD) feeding, we inhibited intestinal lipases in Nile tilapia to investigate the physiological consequences. In the present study, Nile tilapia were firstly fed with HFD (12% fat) for 6 weeks to establish a fatty fish model. Afterwards, Orlistat as a potent intestinal lipase inhibitor was added into the HFD for the following 5-week feeding trial, with two dietary doses (Orlistat16 group, 16 mg/kg body weight; Orlistat32 group, 32 mg/kg body weight). After the trial, both doses of Orlistat treatment significantly reduced intestinal lipase activity, fat absorption, hepatic lipid accumulation, and gene expression of lipogenesis, whereas increased gene expression of lipid catabolism. Moreover, intestinal lipase inhibition increased immune enzyme activities, antioxidant capacity, and gene expression of anti-inflammatory cytokines, whereas lowered gene expression of pro-inflammatory cytokines. Besides, Orlistat could also improve the structure of the intestine and increase expression of intestinal tight-coupling protein. Taken together, intestinal lipase inhibition alleviated the adverse effects caused by HFD in Nile tilapia. Thus, intestinal lipases played key roles in absorbing dietary lipid and could be a promising target in regulating systemic lipid metabolism in fish.

Inhibited autophagy impairs systemic nutrient metabolism in Nile tilapia.

Autophagy is a conserved cellular degradation process through which intracellular components are degraded by the lysosome, but its roles in fish metabolism have not been studied in depth. Therefore, the present study aimed to investigate whether autophagy plays a key role in maintaining metabolic homeostasis in fish. In an 8-week feeding trial, Nile tilapia were fed either a control diet with medium fat and medium carbohydrate (Control), or a control diet supplemented with a classic autophagy inhibitor (chloroquine, CQ). CQ supplementation significantly inhibited autophagy and impaired fish growth and protein synthesis, and the glycolysis was stimulated, accompanied by fat accumulation, high oxidative stress and inflammation. Physiological status and gene expressions suggested that impaired autophagy might be at least one cause of the metabolic diseases which has been commonly seen in aquaculture. These results indicate that inhibition of autophagy could significantly affect the metabolism of lipid, carbohydrate and protein in fish; hence, autophagy could play important roles in maintaining homeostasis of nutrient metabolism in cultured fish.