A global perspective on the crosstalk between saturated fatty acids and Toll-like receptor 4 in the etiology of inflammation and insulin resistance

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.

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

Scientific Reports ◽

10.1038/s41598-021-85018-7 ◽

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.

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