4-PBA Attenuates Fat Accumulation in Cultured Spotted Seabass Fed High-Fat-Diet via Regulating Endoplasmic Reticulum Stress

Excessive fat accumulation is a common phenomenon in cultured fish, which can cause metabolic disease such as fatty liver. However, the relative regulatory approach remains to be explored. Based on this, two feeding trials were conducted. Firstly, fish were fed either a normal-fat diet (NFD) or a high-fat diet (HFD) for eight weeks and sampled at the 2nd, 4th, 6th, and 8th week after feeding (Experiment I). In the first four weeks, fish fed an HFD grew faster than those fed an NFD. Conversely, the body weight and weight gain were higher in the NFD group at the 6th and 8th weeks. Under light and transmission electron microscopes, fat accumulation of the liver was accompanied by an obvious endoplasmic reticulum (ER) swell. Accordingly, the expressions of atf-6, ire-1, perk, eif-2 alpha, atf-4, grp78, and chop showed that ER stress was activated at the 6th and 8th weeks. In Experiment II, 50 mg/kg 4-PBA (an ERs inhibitor) was supplemented to an HFD; this was named the 4-PBA group. Then, fish was fed with an NFD, an HFD, and a 4-PBA diet for eight weeks. As the result, the excessive fat deposition caused by an HFD was reversed by 4-PBA. The expression of ER stress-related proteins CHOP and GRP78 was down-regulated by 4-PBA, and the transmission electron microscope images also showed that 4-PBA alleviated ER stress induced by the feeding of an HFD. Furthermore, 4-PBA administration down-regulated SREBP-1C/ACC/FAS, the critical pathways of fat synthesis. In conclusion, the results confirmed that ER stress plays a contributor role in the fat deposition by activating the SREBP-1C/ACC/FAS pathway. 4-PBA as an ER stress inhibitor could reduce fat deposition caused by an HFD via regulating ER stress.

Automated summary

Excessive fat accumulation is common in cultured fish. This study investigates the role of endoplasmic reticulum stress in fat deposition and finds that 4-PBA, an endoplasmic reticulum stress inhibitor, can reduce fat accumulation caused by a high-fat diet.