Indispensable role of PGC1α signaling in lipid and carbohydrate metabolism of fish PPARα activation.

Unlike predictability in mammals, the responses of PPARα activation treatment in fish varies between different fish species. Existing results indicated that the varied effects may result from fish feeding habits difference within their varied dietary protein content, while the exact mechanism remains obscure. In this study, we conducted an in vivo 8-week trial of low protein 30 % (LP) or high protein 38 % (HP) diet fed tilapia (8.83 ± 0.02 g) supplemented with or without fenofibrate and in vitro 24-h of BCAA (leucine, valine and isoleucine) treated primary cell trial, aiming to reveal the unknown mechanism. The in vivo results showed that, in LP group, fenofibrate significantly increased serum levels of TG, glucose, AST, ALT, MDA and liver TG (P < 0.05), while decreased liver, muscle and serum BCAA, liver mitochondria quantity, glucose tolerance (P < 0.05). Moreover, fenofibrate notably lifted the hepatic bckdha, bckdhb, mff, fis, fas and pparγ expression (P < 0.05), while decreased genes expression of pgc1α, tfam, parkin, pink, foxo3a, sod2, cat, ir and irs (P < 0.05). No great impact was found in aco, cyp4a3 and cytb (P > 0.05). In HP group, fenofibrate improved lipid and glucose metabolism along with unaltered BCAA, increased expression of aco, cytb, cpt1a, pparβ, foxo3a, sod2, nrf1, mfn1 and fis (P < 0.05). In vitro findings revealed that the PGC1α and PPARα could be activated by BCAA, particular for leucine (P < 0.05). Taken together, we conclude that: 1) increased lipid deposition, lipid peroxidation, liver damage and glucose intolerance in fenofibrate-LP group could be ascribed to decreased BCAA and done through PGC1α/FOXO3, PGC1α/MQC regulation; 2) improved lipid-lowering and glucose tolerance in fenofibrate-HP group would be attributed to the enhanced PGC1α/MQC, organelles proliferation and fatty acid β-oxidation.