Low‐ω3 Fatty Acid and Soy Protein Attenuate Alcohol‐Induced Fatty Liver and Injury by Regulating the Opposing Lipid Oxidation and Lipogenic Signaling Pathways

Abstract

Chronic ethanol-induced downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1β) affect hepatic lipid oxidation and lipogenesis, respectively, leading to fatty liver injury. Low-ω3 fatty acid (Low-ω3FA) that primarily regulates PGC1α and soy protein (SP) that seems to have its major regulatory effect on PGC1β were evaluated for their protective effects against ethanol-induced hepatosteatosis in rats fed with Lieber-deCarli control or ethanol liquid diets with high or low ω3FA fish oil and soy protein. Low-ω3FA and SP opposed the actions of chronic ethanol by reducing serum and liver lipids with concomitant decreased fatty liver. They also prevented the downregulation of hepatic Sirtuin 1 (SIRT1) and PGC1α and their target fatty acid oxidation pathway genes and attenuated the upregulation of hepatic PGC1β and sterol regulatory element-binding protein 1c (SREBP1c) and their target lipogenic pathway genes via the phosphorylation of 5′ adenosine monophosphate-activated protein kinase (AMPK). Thus, these two novel modulators attenuate ethanol-induced hepatosteatosis and consequent liver injury potentially by regulating the two opposing lipid oxidation and lipogenic pathways.

Chronic intake of high-dose of blueberry leaf extract does not augment the harmful effects of ethanol in rats

“…Based on our previous single dose studies, we set the dose of 3% BLEx. The animal model was created according to the methods described by Reyes-Gordillo et al (Reyes-Gordillo et al, 2016). The serum AST, ALT, total protein, albumin levels, and A/G ratio, which are the indices of liver injury did not change when the rats were fed with 5% ethanol for 5 weeks, demonstrating that there was no ethanol-induced liver injury.…”

Thymosin β4 Prevents Oxidative Stress, Inflammation, and Fibrosis in Ethanol‐ and LPS‐Induced Liver Injury in Mice

“…Numerous studies have established that a high ω -3 polyunsaturated fatty acid (PUFA) diet is more harmful in causing alcoholic liver injury than saturated fat diets [ 45 – 49 ]. We have previously shown that low ω -3 PUFA, but not high ω -3 PUFA, attenuates alcoholic liver injury [ 50 ]. Moreover, Chang et al have demonstrated that while there was no significant increase in serum AST and ALT levels in chow-fed mice that were administered with a single dose of ethanol (5 g/kg) gavage, there was a significant increase in the serum AST and ALT levels in high-fat diet fed mice that were administered with a single dose ethanol (5 g/kg) gavage [ 51 ].…”

Peer Review #1 of "Chronic intake of high-dose of blueberry leaf extract does not augment the harmful effects of ethanol in rats (v0.1)"

“…Based on our previous single dose studies, we set the dose of 3% BLEx. The animal model was created according to the methods described by Reyes-Gordillo et al (Reyes-Gordillo et al, 2016). The serum AST, ALT, total protein, albumin levels, and A/G ratio, which are the indices of liver injury did not change when the rats were fed with 5% ethanol for 5 weeks, demonstrating that there was no ethanol-induced liver injury.…”