Dietary saturated fatty acids prime the NLRP3 inflammasome via TLR4 in dendritic cells-implications for diet-induced insulin resistance

2012 ◽  
Vol 56 (8) ◽  
pp. 1212-1222 ◽  
Author(s):  
Clare M. Reynolds ◽  
Fiona C. McGillicuddy ◽  
Karen A. Harford ◽  
Orla M. Finucane ◽  
Kingston H. G. Mills ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Dendritic Cells ◽  
Nlrp3 Inflammasome ◽  
Saturated Fatty Acids

scholarly journals Circulating fatty acid profiles are associated with protein energy wasting in maintenance hemodialysis patients: a cross-sectional study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ban-Hock Khor ◽  
◽  
Sharmela Sahathevan ◽  
Ayesha Sualeheen ◽  
Mohammad Syafiq Md Ali ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Nutritional Status ◽  
Serum Albumin ◽  
Saturated Fatty Acids ◽  
Maintenance Hemodialysis ◽  
Model Assessment ◽  
Cross Sectional ◽  
Markers Of Inflammation

AbstractThe metabolic impact of circulating fatty acids (FAs) in patients requiring hemodialysis (HD) is unknown. We investigated the associations between plasma triglyceride (TG) FAs and markers of inflammation, insulin resistance, nutritional status and body composition. Plasma TG-FAs were measured using gas chromatography in 341 patients on HD (age = 55.2 ± 14.0 years and 54.3% males). Cross-sectional associations of TG-FAs with 13 markers were examined using multivariate linear regression adjusted for potential confounders. Higher levels of TG saturated fatty acids were associated with greater body mass index (BMI, r = 0.230), waist circumference (r = 0.203), triceps skinfold (r = 0.197), fat tissue index (r = 0.150), serum insulin (r = 0.280), and homeostatic model assessment of insulin resistance (r = 0.276), but lower malnutrition inflammation score (MIS, r =  − 0.160). Greater TG monounsaturated fatty acid levels were associated with lower lean tissue index (r =  − 0.197) and serum albumin (r =  − 0.188), but higher MIS (r = 0.176). Higher levels of TG n-3 polyunsaturated fatty acids (PUFAs) were associated with lower MIS (r =  − 0.168) and interleukin-6 concentrations (r =  − 0.115). Higher levels of TG n-6 PUFAs were associated with lower BMI (r =  − 0.149) but greater serum albumin (r = 0.112). In conclusion, TG monounsaturated fatty acids were associated with poor nutritional status, while TG n-3 PUFAs were associated with good nutritional status. On the other hand, TG saturated fatty acids and TG n-6 PUFAs had both favorable and unfavorable associations with nutritional parameters.

scholarly journals Palmitic acid promotes resistin-induced insulin resistance and inflammation in SH-SY5Y human neuroblastoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hamza Amine ◽  
Yacir Benomar ◽  
Mohammed Taouis
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Palmitic Acid ◽  
Lipid Rafts ◽  
Acid Treatment ◽  
Protective Action ◽  
Saturated Fatty Acids ◽  
Membrane Lipid ◽  
Human Neuroblastoma ◽  
Peripheral Tissues

AbstractSaturated fatty acids such as palmitic acid promote inflammation and insulin resistance in peripheral tissues, contrasting with the protective action of polyunsaturated fatty acids such docosahexaenoic acid. Palmitic acid effects have been in part attributed to its potential action through Toll-like receptor 4. Beside, resistin, an adipokine, also promotes inflammation and insulin resistance via TLR4. In the brain, palmitic acid and resistin trigger neuroinflammation and insulin resistance, but their link at the neuronal level is unknown. Using human SH-SY5Yneuroblastoma cell line we show that palmitic acid treatment impaired insulin-dependent Akt and Erk phosphorylation whereas DHA preserved insulin action. Palmitic acid up-regulated TLR4 as well as pro-inflammatory cytokines IL6 and TNFα contrasting with DHA effect. Similarly to palmitic acid, resistin treatment induced the up-regulation of IL6 and TNFα as well as NFκB activation. Importantly, palmitic acid potentiated the resistin-dependent NFkB activation whereas DHA abolished it. The recruitment of TLR4 to membrane lipid rafts was increased by palmitic acid treatment; this is concomitant with the augmentation of resistin-induced TLR4/MYD88/TIRAP complex formation mandatory for TLR4 signaling. In conclusion, palmitic acid increased TLR4 expression promoting resistin signaling through TLR4 up-regulation and its recruitment to membrane lipid rafts.

Insulin resistance directly correlates with increased saturated fatty acids in skeletal muscle triglycerides

Metabolism ◽  
2000 ◽  
Vol 49 (2) ◽  
pp. 220-224 ◽  
Author(s):  
M. Manco ◽  
A.V. Greco ◽  
E. Capristo ◽  
D. Gniuli ◽  
A. De Gaetano ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Saturated Fatty Acids

scholarly journals Saturated Fatty Acids Promote GDF15 Expression in Human Macrophages through the PERK/eIF2/CHOP Signaling Pathway

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3771
Author(s):  
Laurent L’homme ◽  
Benan Pelin Sermikli ◽  
Bart Staels ◽  
Jacques Piette ◽  
Sylvie Legrand-Poels ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Er Stress ◽  
Signaling Pathway ◽  
Promoter Region ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Growth Differentiation Factor 15 ◽  
Human Macrophages ◽  
Primary Monocyte

Growth differentiation factor-15 (GDF-15) and its receptor GFRAL are both involved in the development of obesity and insulin resistance. Plasmatic GDF-15 level increases with obesity and is positively associated with disease progression. Despite macrophages have been recently suggested as a key source of GDF-15 in obesity, little is known about the regulation of GDF-15 in these cells. In the present work, we sought for potential pathophysiological activators of GDF15 expression in human macrophages and identified saturated fatty acids (SFAs) as strong inducers of GDF15 expression and secretion. SFAs increase GDF15 expression through the induction of an ER stress and the activation of the PERK/eIF2/CHOP signaling pathway in both PMA-differentiated THP-1 cells and in primary monocyte-derived macrophages. The transcription factor CHOP directly binds to the GDF15 promoter region and regulates GDF15 expression. Unlike SFAs, unsaturated fatty acids do not promote GDF15 expression and rather inhibit both SFA-induced GDF15 expression and ER stress. These results suggest that free fatty acids may be involved in the control of GDF-15 and provide new molecular insights about how diet and lipid metabolism may regulate the development of obesity and T2D.

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

2010 ◽  
Vol 298 (6) ◽  
pp. E1122-E1130 ◽  
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.

scholarly journals Saturated Fatty Acids Undergo Intracellular Crystallization and Activate the NLRP3 Inflammasome in Macrophages

2018 ◽  
Vol 38 (4) ◽  
pp. 744-756 ◽  
Author(s):  
Tadayoshi Karasawa ◽  
Akira Kawashima ◽  
Fumitake Usui-Kawanishi ◽  
Sachiko Watanabe ◽  
Hiroaki Kimura ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Nlrp3 Inflammasome ◽  
Saturated Fatty Acids

scholarly journals Serum saturated fatty acids containing triacylglycerols are better markers of insulin resistance than total serum triacylglycerol concentrations

Diabetologia ◽  
2009 ◽  
Vol 52 (4) ◽  
pp. 684-690 ◽  
Author(s):  
A. Kotronen ◽  
V. R. Velagapudi ◽  
L. Yetukuri ◽  
J. Westerbacka ◽  
R. Bergholm ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Saturated Fatty Acids ◽  
Total Serum
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