Neutral ceramidase activity inhibition is involved in palmitate-induced apoptosis in INS-1 cells

Luo, Fen; Feng, Yamin; Ma, Hongbing; Liu, Chao; Chen, Guofang; Xiao, Wei; Mao, Xiaodong; Li, Xingjia; Xu, Yuehua; Tang, Shan; Wen, Hong-Hua; Jin, Junfei; Zhu, Qun

doi:10.1507/endocrj.ej16-0512

Cited by 15 publications

(14 citation statements)

References 26 publications

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“…In addition, lipotoxicity induced by prolonged elevated FFAs, particularly saturated FFAs such as palmitate, leads to β -cell apoptosis and dysfunction [ 39 , 40 ]. In agreement with previous studies [ 41 , 42 ], our results showed that exposure to palmitate-induced significant cell death of Ins-1 cells. In addition, palmitate treatment reduced insulin secretion in Ins-1 cells, zebrafish β -cells, and isolated mouse islets.…”

Section: Discussionsupporting

confidence: 93%

Polysiphonia japonica Extract Attenuates Palmitate‐Induced Toxicity and Enhances Insulin Secretion in Pancreatic Beta‐Cells

Cha

Kim

Hwang

et al. 2018

Oxidative Medicine and Cellular Longevity

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Beta-cell loss is a major cause of the pathogenesis of diabetes. Elevated levels of free fatty acids may contribute to the loss of β-cells. Using a transgenic zebrafish, we screened ~50 seaweed crude extracts to identify materials that protect β-cells from free fatty acid damage. We found that an extract of the red seaweed Polysiphonia japonica (PJE) had a β-cell protective effect. We examined the protective effect of PJE on palmitate-induced damage in β-cells. PJE was found to preserve cell viability and glucose-induced insulin secretion in a pancreatic β-cell line, Ins-1, treated with palmitate. Additionally, PJE prevented palmitate-induced insulin secretion dysfunction in zebrafish embryos and mouse primary islets and improved insulin secretion in β-cells against palmitate treatment. These findings suggest that PJE protects pancreatic β-cells from palmitate-induced damage. PJE may be a potential therapeutic functional food for diabetes.

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Section: Discussionsupporting

confidence: 93%

Polysiphonia japonica Extract Attenuates Palmitate‐Induced Toxicity and Enhances Insulin Secretion in Pancreatic Beta‐Cells

Cha

Kim

Hwang

et al. 2018

Oxidative Medicine and Cellular Longevity

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“…Exposure to elevated levels of the saturated FA palmitate induces apoptosis in a range of cells including 3T3 fibroblasts (Kamili et al ., 2015), peripheral blood mononuclear cells (RostamiRad et al ., 2018), human cardiac progenitor cells (Leonardini et al ., 2017), pancreatic β cells (Boslem et al ., 2011; Luo et al ., 2017), macrophages (Kim et al ., 2017), and hepatocytes (Penke et al ., 2017). Palmitate also impairs MDA‐MB‐231 cell proliferation and activates apoptosis (Baumann et al ., 2016; Hardy et al ., 2000, 2003; Kourtidis et al ., 2009; Wu et al ., 2017) via a number of mechanisms, including ER stress (Baumann et al ., 2016; Boslem et al ., 2011), impaired autophagy (RostamiRad et al ., 2018; Wu et al ., 2017), altered NAD metabolism (Penke et al ., 2017), and ceramide synthesis (Luo et al ., 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Palmitate also impairs MDA‐MB‐231 cell proliferation and activates apoptosis (Baumann et al ., 2016; Hardy et al ., 2000, 2003; Kourtidis et al ., 2009; Wu et al ., 2017) via a number of mechanisms, including ER stress (Baumann et al ., 2016; Boslem et al ., 2011), impaired autophagy (RostamiRad et al ., 2018; Wu et al ., 2017), altered NAD metabolism (Penke et al ., 2017), and ceramide synthesis (Luo et al ., 2017). Importantly, many of the deleterious effects of palmitate on cellular function are mitigated by cotreatment with other FAs, in particular the monounsaturated FA oleate (Colvin et al ., 2017; Kim et al ., 2017; Penke et al ., 2017; Sargsyan et al ., 2016), which itself is pro‐proliferative and activates phosphoinositide 3‐kinase signaling (Hardy et al ., 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Exposure to elevated levels of the saturated FA palmitate induces apoptosis in a range of cells including 3T3 fibroblasts (Kamili et al, 2015), peripheral blood mononuclear cells (RostamiRad et al, 2018), human cardiac progenitor cells (Leonardini et al, 2017), pancreatic b cells (Boslem et al, 2011;Luo et al, 2017), macrophages (Kim et al, 2017), and hepatocytes (Penke et al, 2017). Palmitate also impairs MDA-MB-231 cell proliferation and activates apoptosis (Baumann et al, 2016;Hardy et al, 2000Hardy et al, , 2003Kourtidis et al, 2009;Wu et al, 2017) via a number of mechanisms, including ER stress (Baumann et al, 2016;Boslem et al, 2011), impaired autophagy (RostamiRad et al, 2018Wu et al, 2017), altered NAD metabolism (Penke et al, 2017), and ceramide synthesis (Luo et al, 2017). Importantly, many of the deleterious effects of palmitate on cellular function are mitigated by cotreatment with other FAs, in particular the monounsaturated FA oleate (Colvin et al, 2017;Kim et al, 2017;Penke et al, 2017;Sargsyan et al, 2016), which itself is pro-proliferative and activates phosphoinositide 3kinase signaling (Hardy et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

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Heterogeneity of fatty acid metabolism in breast cancer cells underlies differential sensitivity to palmitate‐induced apoptosis

et al. 2018

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Breast cancer (BrCa) metabolism is geared toward biomass synthesis and maintenance of reductive capacity. Changes in glucose and glutamine metabolism in BrCa have been widely reported, yet the contribution of fatty acids (FAs) in BrCa biology remains to be determined. We recently reported that adipocyte coculture alters MCF‐7 and MDA‐MB‐231 cell metabolism and promotes proliferation and migration. Since adipocytes are FA‐rich, and these FAs are transferred to BrCa cells, we sought to elucidate the FA metabolism of BrCa cells and their response to FA‐rich environments. MCF‐7 and MDA‐MB‐231 cells incubated in serum‐containing media supplemented with FAs accumulate extracellular FAs as intracellular triacylglycerols (TAG) in a dose‐dependent manner, with MDA‐MB‐231 cells accumulating more TAG. The differences in TAG levels were a consequence of distinct differences in intracellular partitioning of FAs, and not due to differences in the rate of FA uptake. Specifically, MCF‐7 cells preferentially partition FAs into mitochondrial oxidation, whereas MDA‐MB‐231 cells partition FAs into TAG synthesis. These differences in intracellular FA handling underpin differences in the sensitivity to palmitate‐induced lipotoxicity, with MDA‐MB‐231 cells being highly sensitive, whereas MCF‐7 cells are partially protected. The attenuation of palmitate‐induced lipotoxicity in MCF‐7 cells was reversed by inhibition of FA oxidation. Pretreatment of MDA‐MB‐231 cells with FAs increased TAG synthesis and reduced palmitate‐induced apoptosis. Our results provide novel insight into the potential influences of obesity on BrCa biology, highlighting distinct differences in FA metabolism in MCF‐7 and MDA‐MB‐231 cells and how lipid‐rich environments modulate these effects.

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“…Neutral ceramidase-degradating ceramides are suppressed by saturated FAs; thus, when there is an excess of saturated FAs, ceramides are accumulated in β-cells [ 212 ]. This leads to the facilitation of apoptosis that is promoted by saturated FAs.…”

Section: Pathology Related To Lcfasmentioning

confidence: 99%

Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity

et al. 2018

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Fatty acid (FA)-stimulated insulin secretion (FASIS) is reviewed here in contrast to type 2 diabetes etiology, resulting from FA overload, oxidative stress, intermediate hyperinsulinemia, and inflammation, all converging into insulin resistance. Focusing on pancreatic islet β-cells, we compare the physiological FA roles with the pathological ones. Considering FAs not as mere amplifiers of glucose-stimulated insulin secretion (GSIS), but as parallel insulin granule exocytosis inductors, partly independent of the KATP channel closure, we describe the FA initiating roles in the prediabetic state that is induced by retardations in the glycerol-3-phosphate (glucose)-promoted glycerol/FA cycle and by the impaired GPR40/FFA1 (free FA1) receptor pathway, specifically in its amplification by the redox-activated mitochondrial phospholipase, iPLA2γ. Also, excessive dietary FAs stimulate intestine enterocyte incretin secretion, further elevating GSIS, even at low glucose levels, thus contributing to diabetic hyperinsulinemia. With overnutrition and obesity, the FA overload causes impaired GSIS by metabolic dysbalance, paralleled by oxidative and metabolic stress, endoplasmic reticulum stress and numerous pro-apoptotic signaling, all leading to decreased β-cell survival. Lipotoxicity is exerted by saturated FAs, whereas ω-3 polyunsaturated FAs frequently exert antilipotoxic effects. FA-facilitated inflammation upon the recruitment of excess M1 macrophages into islets (over resolving M2 type), amplified by cytokine and chemokine secretion by β-cells, leads to an inevitable failure of pancreatic β-cells.

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Neutral ceramidase activity inhibition is involved in palmitate-induced apoptosis in INS-1 cells

Cited by 15 publications

References 26 publications

Polysiphonia japonica Extract Attenuates Palmitate‐Induced Toxicity and Enhances Insulin Secretion in Pancreatic Beta‐Cells

Polysiphonia japonica Extract Attenuates Palmitate‐Induced Toxicity and Enhances Insulin Secretion in Pancreatic Beta‐Cells

Heterogeneity of fatty acid metabolism in breast cancer cells underlies differential sensitivity to palmitate‐induced apoptosis

Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity

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