Oleic acid-induced perilipin 5 expression and lipid droplets formation are regulated by the PI3K/PPARα pathway in HepG2 cells

Zhong, Wenxia; Fan, Bin; Cong, Huiying; Wang, Tianyu; Gu, Jianqiu

doi:10.1139/apnm-2018-0729

Cited by 20 publications

(16 citation statements)

References 37 publications

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“…The detailed mechanism of the antioxidant role of Plin5 via regulating Nrf2-ARE system in β-cells was explored preliminary in the present study. In some tissues, Plin5 has been reported to involve in the regulation of PI3K/Akt or MAPK pathways (p38 MAPK, ERK, and JNK) (21,24,40,44,49), which is the upstream modulators of Nrf2 in pancreatic β-cells (39,41). As evidenced by prior studies, excess ROS production and oxidative stress results in the activation of apoptotic p38 MAPK and JNK signaling, whereas activation of antiapoptotic PI3K/Akt and ERK pathways facilitates the translocation of Nrf2 into the nucleus, thereby activating the Nrf2/ARE pathway and alleviating oxidative damage (50,51).…”

Section: Discussionmentioning

confidence: 99%

Perilipin 5 Reduces Oxidative Damage Associated With Lipotoxicity by Activating the PI3K/ERK-Mediated Nrf2-ARE Signaling Pathway in INS-1 Pancreatic β-Cells

et al. 2020

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Oxidative stress induced by free fatty acid overload in pancreatic β-cells is a potential contributory factor to dysfunction of insulin secretion and apoptotic cell death. Perilipin 5 (Plin5) has been reported to ameliorate oxidative stress-mediated damage in non-insulin-secreting tissues. We tested the hypothesis that Plin5 plays a similar role in pancreatic β-cells, which are extremely sensitive to oxidative stress. Here, our in vitro data showed that Plin5-mediated alleviation of palmitate-triggered apoptosis involves the mitochondrial pathway. And the protective role of Plin5 on β-cells was partially dependent on its modulation in oxidative stress. Upregulation of Plin5 in INS-1 cells decreased reactive oxygen species production, enhanced cellular glutathione levels, and induced expression of antioxidant enzymes glutamate-cysteine ligase catalytic subunit and heme oxygenase-1. However, knocking out of Plin5 abolished all of these beneficial effects. Furthermore, by using the O 2− scavenger MnTMPyP, we verified that altering Plin5 expression impacted lipotoxic cell death partially via modulating oxidative stress. Mechanistic experiments revealed that Plin5 induced Nrf2-ARE system, a master regulator in the cellular adaptive response to oxidative stress, by activating PI3K/Akt and ERK signal pathways, contributing to the increase of antioxidant defense and consequently improving β-cell function and survival in the presence of lipotoxic oxidative stress. Overall, our findings indicate that Plin5 abrogates oxidative damage in INS-1 β-cells during lipotoxic stress partially through the enhancement of antioxidant defense involving the PI3K/Akt and ERK mediated Nrf2-ARE system.

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Section: Discussionmentioning

confidence: 99%

Perilipin 5 Reduces Oxidative Damage Associated With Lipotoxicity by Activating the PI3K/ERK-Mediated Nrf2-ARE Signaling Pathway in INS-1 Pancreatic β-Cells

et al. 2020

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“…Recently, it was reported that LD formation after stimulation with oleic acid (OA) leads to activation of PLIN5 in human liver cancer HepG2 cells via the PI3K/PPARα pathway [64].…”

Section: The Role Of Plin5 In Lipid Metabolism and Nafldmentioning

confidence: 99%

“…Recently, it was reported that LD formation after stimulation with oleic acid (OA) leads to activation of PLIN5 in human liver cancer HepG2 cells via the PI3K/PPARα pathway [ 64 ]. In the respective study, it was demonstrated that the PPAR

inhibitor GW6471 decreased the levels of PLIN5 in a dose-dependent manner.…”

Section: The Role Of Plin5 In Lipid Metabolism and Nafldmentioning

confidence: 99%

“…Moreover, the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 diminished the levels of PLIN5 mRNA in HepG2 cells. Thus the combination of OA treatment and inhibition of PI3K or PPARα activities showed a decrease in LDs, revealing the partial role of PLIN5 in the control of LD formation [ 64 ]. In this context, the PI3K pathway is also involved in ER stress.…”

Section: The Role Of Plin5 In Lipid Metabolism and Nafldmentioning

confidence: 99%

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Understanding the Role of Perilipin 5 in Non-Alcoholic Fatty Liver Disease and Its Role in Hepatocellular Carcinoma: A Review of Novel Insights

Sanchez

Krizanac

Weiskirchen

et al. 2021

IJMS

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Consumption of high-calorie foods, such as diets rich in fats, is an important factor leading to the development of steatohepatitis. Several studies have suggested how lipid accumulation creates a lipotoxic microenvironment for cells, leading cells to deregulate their transcriptional and translational activity. This deregulation induces the development of liver diseases such as non-alcoholic fatty liver disease (NAFLD) and subsequently also the appearance of hepatocellular carcinoma (HCC) which is one of the deadliest types of cancers worldwide. Understanding its pathology and studying new biomarkers with better specificity in predicting disease prognosis can help in the personalized treatment of the disease. In this setting, understanding the link between NAFLD and HCC progression, the differentiation of each stage in between as well as the mechanisms underlying this process, are vital for development of new treatments and in exploring new therapeutic targets. Perilipins are a family of five closely related proteins expressed on the surface of lipid droplets (LD) in several tissues acting in several pathways involved in lipid metabolism. Recent studies have shown that Plin5 depletion acts protectively in the pathogenesis of liver injury underpinning the importance of pathways associated with PLIN5. PLIN5 expression is involved in pro-inflammatory cytokine regulation and mitochondrial damage, as well as endoplasmic reticulum (ER) stress, making it critical target of the NAFLD-HCC studies. The aim of this review is to dissect the recent findings and functions of PLIN5 in lipid metabolism, metabolic disorders, and NAFLD as well as the progression of NAFLD to HCC.

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“…PI3K/AKT is a classical pathway involved in insulin resistance, cell growth, and lipid metabolism associated with the inhibition of cholesterol efflux leading to LD formation [229]. In this sense, the participation of the PIK3 signaling pathway in MT-III-induced LDs in macrophages and vascular smooth muscle cells stimulated with MT-III has been demonstrated [167,224].…”

Section: Bothrops Svpla 2s Trigger Lipid Accumulation In Immunocompetent Cellsmentioning

confidence: 99%

Inflammatory Effects of Bothrops Phospholipases A2: Mechanisms Involved in Biosynthesis of Lipid Mediators and Lipid Accumulation

Moreira

Leiguez

Janovits

et al. 2021

Toxins

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Phospholipases A2s (PLA2s) constitute one of the major protein groups present in the venoms of viperid and crotalid snakes. Snake venom PLA2s (svPLA2s) exhibit a remarkable functional diversity, as they have been described to induce a myriad of toxic effects. Local inflammation is an important characteristic of snakebite envenomation inflicted by viperid and crotalid species and diverse svPLA2s have been studied for their proinflammatory properties. Moreover, based on their molecular, structural, and functional properties, the viperid svPLA2s are classified into the group IIA secreted PLA2s, which encompasses mammalian inflammatory sPLA2s. Thus, research on svPLA2s has attained paramount importance for better understanding the role of this class of enzymes in snake envenomation and the participation of GIIA sPLA2s in pathophysiological conditions and for the development of new therapeutic agents. In this review, we highlight studies that have identified the inflammatory activities of svPLA2s, in particular, those from Bothrops genus snakes, which are major medically important snakes in Latin America, and we describe recent advances in our collective understanding of the mechanisms underlying their inflammatory effects. We also discuss studies that dissect the action of these venom enzymes in inflammatory cells focusing on molecular mechanisms and signaling pathways involved in the biosynthesis of lipid mediators and lipid accumulation in immunocompetent cells.

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Oleic acid-induced perilipin 5 expression and lipid droplets formation are regulated by the PI3K/PPARα pathway in HepG2 cells

Cited by 20 publications

References 37 publications

Perilipin 5 Reduces Oxidative Damage Associated With Lipotoxicity by Activating the PI3K/ERK-Mediated Nrf2-ARE Signaling Pathway in INS-1 Pancreatic β-Cells

Perilipin 5 Reduces Oxidative Damage Associated With Lipotoxicity by Activating the PI3K/ERK-Mediated Nrf2-ARE Signaling Pathway in INS-1 Pancreatic β-Cells

Understanding the Role of Perilipin 5 in Non-Alcoholic Fatty Liver Disease and Its Role in Hepatocellular Carcinoma: A Review of Novel Insights

Inflammatory Effects of Bothrops Phospholipases A2: Mechanisms Involved in Biosynthesis of Lipid Mediators and Lipid Accumulation

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