Palmitate-Induced Interleukin-6 Expression in Human Coronary Artery Endothelial Cells

Abstract

Obesity-linked insulin resistance is associated with chronic inflammation and cardiovascular complications. Free fatty acids (FFAs) are prominent candidates for the molecular link between these disorders. In this study, we determined whether FFAs contribute to vascular inflammation via induction of interleukin (IL)-6 in coronary artery endothelial cells (CAECs) and coronary artery smooth muscle cells (CASMCs) and whether this is reflected in vivo. In contrast to our findings regarding IL-6 and gp130 (the glycoprotein of 130 kDa) expression, IL-6 receptor mRNA expression was very low in these cells. Palmitate, but not linoleate, induced a significant increase in IL-6 mRNA expression in CAECs (P < 0.001) and, to a less relevant extent, in CASMCs (P < 0.01). gp130 remained unaffected. As to potency, palmitate was comparable with the IL-6؊inducer IL-1␤. To substantiate our in vitro data, we examined the plasma FFA pattern in 54 healthy human subjects and studied the relation of individual FFAs with plasma IL-6. IL-6 levels correlated with palmitate, but not with other abundant FFAs, even after adjusting for body fat (r ‫؍‬ 0.33, P < 0.05) and total FFAs (r ‫؍‬ 0.29, P < 0.05). We show here that the common plasma FFA palmitate induces high levels of IL-6 in CAECs. Furthermore, palmitate correlates with IL-6 in vivo. This points to a potential contribution of palmitate to vascular inflammation. Diabetes 53: 3209 -3216, 2004

Palmitate induces a pro-inflammatory response in human pancreatic islets that mimics CCL2 expression by beta cells in type 2 diabetes

“…Saturated and unsaturated NEFA have different functional effects in beta cells [40][41][42]. Saturated NEFA are pro-inflammatory in several cell types [43,44] and also cause ER stress [10]. Because palmitate (but not oleate or high glucose) induces ER stress in human islets [10] and there is a crosstalk between ER stress and NF-κB pathways [45][46][47], we explored this mechanism further.…”

Dietary determinants of subclinical inflammation, dyslipidemia and components of the metabolic syndrome in overweight children: a review

“…Palmitate, but not laurate or docosahexanoic acid (DHA), induces IL-6 in adipocytes, 70 skeletal muscle cells 71 and endothelial cells. 72 Palmitate, but not other plasma-free fatty acids, correlates in vivo with IL-6 concentrations, independent of body fat mass. 72 Conjugated linoleic acid (linoleic acid (C18:2) with a conjugated double bond) may also increases the production of IL-6 and other proinflammatory cytokines in adipose tissue.…”

“…72 Palmitate, but not other plasma-free fatty acids, correlates in vivo with IL-6 concentrations, independent of body fat mass. 72 Conjugated linoleic acid (linoleic acid (C18:2) with a conjugated double bond) may also increases the production of IL-6 and other proinflammatory cytokines in adipose tissue. 73 In contrast, n-3 PUFAs may ameliorate the inflammatory response.…”

A genetikai diabeteskockázat hatása a csontanyagcsere–energia-háztartás kapcsolatokra

“…A hyperlipidaemia, az oxidált LDL és foszfolipidek kialakulása és az általuk indukált gyulladásos reakciók játsz-szák az elsődleges szerepet az atherogenesisben [26]. A módosult lipoproteinek a csont ereinek subendothelialis részében -az osteoblastok elsődleges tartózkodási helyén -felszaporodnak, és gyulladásos mikrokörnyeze-tet alakítanak ki.…”