Combination of fatty acids ameliorates exocrine pancreas ER stress induced by saturated fatty acid

Abstract Background Obesity-induced lipotoxicity causes cardiac dysfunction in our modern lifestyle. Previously, we have shown that an increase in cardiomyocyte membrane saturated fatty acid (SFA)/ monounsaturated FA (MUFA) ratio mediates endoplasmic reticulum (ER) stress, which was implicated in the pathogenesis of SFA-induced cardiomyopathy. Furthermore, SFA supressed Sirt1/ stearoyl-CoA desaturase-1 (SCD1, converting enzyme from SFA to MUFA) signaling, which further worsened the membrane SFA/MUFA ratio. Purpose To evaluate the effectiveness of targeting membrane fatty acid composition by MUFA. Methods and results In wild-type mice, 16-weeks SFA-rich high lard diet feeding (HLD) caused activation of PPARα signaling and the accumulation of toxic lipid intermediates (diacylglycerol and ceramide) in the heart to the same extent as a MUFA-rich high olive oil diet feeding (HOD). However, only the HLD impaired Sirt1 activity, SCD1 expression, diastolic function (increased left ventricular end-diastolic pressure (LVEDP) and end-diastolic pressure-volume relationship (EDPVR)), and cardiac remodeling (hypertrophy and fibrosis). Lipidome analysis showed that HLD-induced diastolic dysfunction coincided with an increase in membrane SFA/MUFA ratio and ER stress induction. 8-weeks HOD after 8-weeks HLD (HOD switch) showed the same degree of obesity and PPARα activation with 16-weeks HLD. By contrast, HOD switched heart were less severe Sirt1/SCD1 signaling dysregulation, increased in membrane SFA/MUFA ratio, ER stress, and cardiomyopathy (hypertrophy, fibrosis, and diastolic dysfunction) compared to 16-weeks HLD. Moreover, in cardiomyocyte-specific Sirt1 knockout mice, HOD switched heart also showed less severe increase in membrane SFA/MUFA ratio, ER stress, and cardiomyopathy compared to 16-weeks HLD although decreased SCD1 expression was not changed. Conclusions We demonstrated that MUFA-rich diet counteracted SFA-induced Sirt1/SCD1 signaling dysregulation and prevented SFA-induced increase in membrane SFA/MUFA ratio. Hence, MUFA-rich diet antagonized SFA-induced ER stress and cardiomyopathy even if Sirt1 deactivated heart (e.g., aged heart). Targeting the cardiomyocyte membrane SFA/MUFA ratio by MUFA might have a new therapeutic potential for SFA-induced cardiomyopathy. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): JSPS KAKENHI

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Cultured hypothalamic neurons are resistant to inflammation and insulin resistance induced by saturated fatty acids

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00006.2010 ◽

2010 ◽

Vol 298 (6) ◽

pp. E1122-E1130 ◽

Cited By ~ 51

Author(s):

Sun Ju Choi ◽

Francis Kim ◽

Michael W. Schwartz ◽

Brent E. Wisse

Keyword(s):

Insulin Resistance ◽

Fatty Acids ◽

Fatty Acid ◽

Saturated Fatty Acid ◽

Cell Lines ◽

Saturated Fatty Acids ◽

Neuronal Cell ◽

Acid Exposure ◽

Inflammatory Signaling ◽

Hypothalamic Neurons

Hypothalamic inflammation induced by high-fat feeding causes insulin and leptin resistance and contributes to the pathogenesis of obesity. Since in vitro exposure to saturated fatty acids causes inflammation and insulin resistance in many cultured cell types, we determined how cultured hypothalamic neurons respond to this stimulus. Two murine hypothalamic neuronal cell cultures, N43/5 and GT1–7, were exposed to escalating concentrations of saturated fatty acids for up to 24 h. Harvested cells were evaluated for activation of inflammation by gene expression and protein content. Insulin-treated cells were evaluated for induction of markers of insulin receptor signaling (p-IRS, p-Akt). In both hypothalamic cell lines, inflammation was induced by prototypical inflammatory mediators LPS and TNFα, as judged by induction of IκBα (3- to 5-fold) and IL-6 (3- to 7-fold) mRNA and p-IκBα protein, and TNFα pretreatment reduced insulin-mediated p-Akt activation by 30% ( P < 0.05). By comparison, neither mixed saturated fatty acid (100, 250, or 500 μM for ≤6 h) nor palmitate exposure alone (200 μM for ≤24 h) caused inflammatory activation or insulin resistance in cultured hypothalamic neurons, whereas they did in control muscle and endothelial cell lines. Despite the lack of evidence of inflammatory signaling, saturated fatty acid exposure in cultured hypothalamic neurons causes endoplasmic reticulum stress, induces mitogen-activated protein kinase, and causes apoptotic cell death with prolonged exposure. We conclude that saturated fatty acid exposure does not induce inflammatory signaling or insulin resistance in cultured hypothalamic neurons. Therefore, hypothalamic neuronal inflammation in the setting of DIO may involve an indirect mechanism mediated by saturated fatty acids on nonneuronal cells.

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The Toxic Effects of Fatty Acids and Their Salts on the Balsam Woolly Aphid, Adelgespiceae (Ratz.)

Canadian Journal of Forest Research ◽

10.1139/x75-075 ◽

1975 ◽

Vol 5 (4) ◽

pp. 515-522 ◽

Cited By ~ 19

Author(s):

George S. Puritch

Keyword(s):

Fatty Acids ◽

Oleic Acid ◽

Fatty Acid ◽

Saturated Fatty Acid ◽

Capric Acid ◽

The Other ◽

Toxic Effects ◽

Life Stages ◽

Woolly Aphid ◽

Oleic And Linoleic Acids

Fatty acids and their potassium soaps were screened for their toxicity to different life stages and eggs of the balsam woolly aphid (Adelgespiceae (Ratz.)). The most effective fatty acids for causing aphid mortality were in two major groups, one centering around capric acid (C10) within the low-chain saturated fatty acid series and the other around oleic acid (C18:1), within the unsaturated 18-carbon fatty acids. The potassium soaps were better aphicides than the corresponding acids; the soaps of caprylic, capric, oleic, and linoleic acids were the most effective. Eggs were less sensitive to the soaps than later stages of the aphid, and there was a large variation in their response to the soap treatments. The possibility of using fatty acids and soaps as a control for the balsam woolly aphid is discussed.

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Zat gizi, massa lemak tubuh, dan tekanan darah pada wanita vegetarian dan nonvegetarian berusia 20-30 tahun

JURNAL GIZI INDONESIA ◽

10.14710/jgi.6.1.17-28 ◽

2017 ◽

Vol 6 (1) ◽

pp. 17-28

Author(s):

Stela Maris Adinda Budi Kirana ◽

Etisa Adi Murbawani ◽

Binar Panunggal

Keyword(s):

Blood Pressure ◽

Fatty Acids ◽

Fatty Acid ◽

Polyunsaturated Fatty Acids ◽

Diastolic Blood Pressure ◽

Saturated Fatty Acid ◽

Body Fat ◽

Fat Mass ◽

Monounsaturated Fatty Acids ◽

Body Fat Mass

Background : Vegetarians tend to have a risk of underfat. Several studies have reported that vegetarians have lower fat and higher fiber intake, lower body fat mass and blood pressure than nonvegetarians. There are only few studies about those variabels in 20-30 year-old subject. Objective : To analyze the difference of nutrients intake, body fat mass, and blood pressure between 20-30-year-old vegetarian and nonvegetarian women.Methods : Cross-sectional study design in 26 vegetarian women and 26 nonvegetarian women who was selected by consecutive sampling. Nutrients intake were obtained by Semi Quantitative Food Frequency Questionaire (SQFFQ) and analyzed by Nutrisurvey. Body fat mass was measured using Bioelectrical Impedance Analysis (BIA). Blood pressure was measured using Mercury sphygmomanometer. Data were analyzed using Independent t-test and Mann-Whitney test.Result : There were 38.5% of vegetarians and 3.8% of nonvegetarians classified as underfat. There were 30.7% of vegetarians and 50% of nonvegetarians classified as prehypertension. There were difference in fat (p=0.005), saturated fatty acid (p=0.000), monounsaturated fatty acids (p=0.002), polyunsaturated fatty acids (p=0.043), fiber (p=0.000), potassium (p=0.000), magnesium (p=0.004); body fat mass (p=0.021); and sistolic blood pressure (p=0.004) between both of groups. There weren’t difference energy intake (p=0.098), carbohydrate (p=0.207), protein (p=0.535), sodium (p=0.784), calcium (p=0.798), and diastolic blood pressure (p=0.799) between both of groups.Conclusion : Between vegetarian group and nonvegetarian group, there were difference in fat, saturated fatty acid, monounsaturated fatty acids, polyunsaturated fatty acids, fiber, potassium, magnesium intake; body fat mass; and sistolic blood pressure. However, there weren’t diffference in energy, carbohydrate, protein, sodium, calcium intake, and diastolic blood pressure between vegetarian group and nonvegetarian group

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SELENON (SEPN1) protects skeletal muscle from saturated fatty acid-induced ER stress and insulin resistance

Redox Biology ◽

10.1016/j.redox.2019.101176 ◽

2019 ◽

Vol 24 ◽

pp. 101176 ◽

Cited By ~ 10

Author(s):

Ersilia Varone ◽

Diego Pozzer ◽

Simona Di Modica ◽

Alexander Chernorudskiy ◽

Leonardo Nogara ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Fatty Acid ◽

Er Stress ◽

Saturated Fatty Acid

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Palmitate and oleate exert differential effects on insulin signalling and glucose uptake in human skeletal muscle cells

Endocrine Connections ◽

10.1530/ec-17-0039 ◽

2017 ◽

Vol 6 (5) ◽

pp. 331-339 ◽

Cited By ~ 7

Author(s):

Selina Mäkinen ◽

Yen H Nguyen ◽

Paulina Skrobuk ◽

Heikki A Koistinen

Keyword(s):

Insulin Resistance ◽

Fatty Acids ◽

Fatty Acid ◽

Er Stress ◽

Glucose Uptake ◽

Insulin Signalling ◽

Ros Production ◽

Human Myotubes ◽

Human Skeletal Muscle Cells ◽

Concomitant Exposure

Saturated fatty acids are implicated in the development of insulin resistance, whereas unsaturated fatty acids may have a protective effect on metabolism. We tested in primary human myotubes if insulin resistance induced by saturated fatty acid palmitate can be ameliorated by concomitant exposure to unsaturated fatty acid oleate. Primary human myotubes were pretreated with palmitate, oleate or their combination for 12 h. Glucose uptake was determined by intracellular accumulation of [3H]-2-deoxy-d-glucose, insulin signalling and activation of endoplasmic reticulum (ER) stress by Western blotting, and mitochondrial reactive oxygen species (ROS) production by fluorescent dye MitoSOX. Exposure of primary human myotubes to palmitate impaired insulin-stimulated Akt-Ser473, AS160 and GSK-3β phosphorylation, induced ER stress signalling target PERK and stress kinase JNK 54 kDa isoform. These effects were virtually abolished by concomitant exposure of palmitate-treated myotubes to oleate. However, an exposure to palmitate, oleate or their combination reduced insulin-stimulated glucose uptake. This was associated with increased mitochondrial ROS production in palmitate-treated myotubes co-incubated with oleate, and was alleviated by antioxidants MitoTempo and Tempol. Thus, metabolic and intracellular signalling events diverge in myotubes treated with palmitate and oleate. Exposure of human myotubes to excess fatty acids increases ROS production and induces insulin resistance.

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