Dietary Creatine Reduces Lipid Accumulation by Improving Lipid Catabolism in the Herbivorous Grass Carp, Ctenopharyngodon idella

Herein, our goal was to explore the creatine role in the fat suppression of grass carp (GC). In vivo, four semipurified diets containing 5% lipid (normal diet, ND), 8% lipid (high-fat diet, HFD), $8\%\text{lipid}+1\%\text{creatine}$ ( $\text{HFD}+\text{CR}1$ ), and $8\%\text{lipid}+2\%\text{creatine}$ ( $\text{HFD}+\text{CR}2$ ) were designed and formulated, which were fed to juvenile GC ( $18.51\pm 0.04\text{g}$ ) for 56 days. HFD significantly increased the intraperitoneal fat index as well as the serum and hepatic triglyceride (TG), total cholesterol (TC), and nonesterified fatty acid (NEFA) levels compared to ND; these effects were all attenuated following the addition of creatine in HFD ( $p<0.05$ ). Relative to HFD, $\text{HFD}+\text{CR}2$ markedly enhanced lipid catabolic gene expressions in the hepatopancreas. This included peroxisome proliferator-activated receptor α, adipose TG lipase (atgl), hormone-sensitive lipase, and carnitine palmitoyltransferase (cpt-1). The protein concentrations of mitochondrial respiratory chain complexes I/II/III/IV/V in the hepatopancreas were upregulated in fish fed $\text{HFD}+\text{CR}1$ and $\text{HFD}+\text{CR}2$ diets, relative to the HFD-fed fish diet ( $p<0.05$ ). In vitro, hepatocytes (L8824) preincubated with oleic acid for 24 h were exposed to varying concentrations of creatine (0, 10, 50, 100, 200, and 400 μM) for another 24 h. The number of lipid droplets in each cell remarkably decreased as the concentration of creatine increased in the medium ( $p<0.05$ ). Creatine also markedly enhanced the relative transcript levels of genes related to lipolysis (such as agtl), β-oxidation (such as cpt-1 and acyl-CoA dehydrogenase very long chain), and the mitochondrial respiratory chain (such as succinate dehydrogenase complex subunit A and cytochrome c-1). Collectively, the study demonstrates that dietary creatine can suppress lipid accumulation and increase lipid catabolic capacity in GC.