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

Abstract

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-2α, 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.

4-Phenyl-butyric Acid Inhibits Japanese Encephalitis Virus Replication via Inhibiting Endoplasmic Reticulum Stress Response

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Unfolded protein response suppression potentiates LPS-induced barrier dysfunction and inflammation in bovine pulmonary artery endothelial cells

“…Lipopolysaccharides activates Toll-like receptor 4 (TLR-4 receptor), to induce inflammation, and has been extensively used to inflict lung injury in vitro , as well as in vivo. 10 , 11 4-PBA is a chemical chaperone which prevents the aggregation of misfolded proteins and reduces endoplasmic reticulum stress. 12 …”

Phenylbutyric acid inhibits hypoxia‐induced trophoblast apoptosis and autophagy in preeclampsia via the PERK/ATF‐4/CHOP pathway

“…Phenylbutyric acid (4-PBA) is a low-toxicity short-chain aromatic fatty acid with molecular chaperone activity (Duran et al, 2022). 4-PBA has been shown to repair or reverse protein misfolding, stabilize protein conformation, and establish normal protein space structure, thereby alleviating ERS (Pao et al, 2021;Xia et al, 2022). 4-PBA plays an important role as an ERS inhibitor in a variety of diseases (Bhardwaj et al, 2022).…”

“…4-PBA has been shown to repair or reverse protein misfolding, stabilize protein conformation, and establish normal protein space structure, thereby alleviating ERS (Pao et al, 2021;Xia et al, 2022). 4-PBA plays an important role as an ERS inhibitor in a variety of diseases (Bhardwaj et al, 2022). 4-PBA has also been found to effectively improve ERS in hepatocytes by inhibiting the PERK/ ATF-4/CHOP pathway (Guo, Hassan, et al, 2017).…”