Additive Regulation of Adiponectin Expression by the Mediterranean Diet Olive Oil Components Oleic Acid and Hydroxytyrosol in Human Adipocytes

Abstract

Adiponectin, an adipocyte-derived insulin-sensitizing and anti-inflammatory hormone, is suppressed in obesity through mechanisms involving chronic inflammation and oxidative stress. Olive oil consumption is associated with beneficial cardiometabolic actions, with possible contributions from the antioxidant phenol hydroxytyrosol (HT) and the monounsaturated fatty acid oleic acid (OA, 18:1n-9 cis), both possessing anti-inflammatory and vasculo-protective properties. We determined the effects of HT and OA, alone and in combination, on adiponectin expression in human and murine adipocytes under pro-inflammatory conditions induced by the cytokine tumor necrosis factor(TNF)-α. We used human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes and murine 3T3-L1 adipocytes as cell model systems, and pretreated them with 1-100 μmol/L OA, 0.1-20 μmol/L HT or OA plus HT combination before stimulation with 10 ng/mL TNF-α. OA or HT significantly (P<0.05) prevented TNF-α-induced suppression of total adiponectin secretion (by 42% compared with TNF-α alone) as well as mRNA levels (by 30% compared with TNF-α alone). HT and OA also prevented—by 35%—TNF-α-induced downregulation of peroxisome proliferator-activated receptor PPARγ. Co-treatment with HT and OA restored adiponectin and PPARγ expression in an additive manner compared with single treatments. Exploring the activation of JNK, which is crucial for both adiponectin and PPARγ suppression by TNF-α, we found that HT and OA additively attenuated TNF-α-stimulated JNK phosphorylation (up to 55% inhibition). In conclusion, the virgin olive oil components OA and HT, at nutritionally relevant concentrations, have additive effects in preventing adiponectin downregulation in inflamed adipocytes through an attenuation of JNK-mediated PPARγ suppression.

The pro-/anti-inflammatory effects of different fatty acids on visceral adipocytes are partially mediated by GPR120

“…However, in another study, oleic acid had no effect on the TNF-α and IL-10 mRNA expression [17]. Also, in 3T3-L1 adipocytes exposure to oleic acid resulted in increased adiponectin gene expression [33] and prevented TNF-α-induced suppression of adiponectin mRNA levels in human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes and murine 3T3-L1 adipocytes [34]. A meta-analysis of intervention trials provided evidence that a diet with monounsaturated FAs decreased inflammation [35].…”

Extra virgin olive oil: More than a healthy fat

“…Results of the PREDIMED study reported that chronic consumption of a Mediterranean diet, rich in EVOO, led a reduction in C-reactive protein (CRP), interleukin-6 (IL-6) and other pro-inflammatory interleukin levels in subjects with high cardiovascular risk [12,13], while 180 patients with metabolic syndrome exhibited reduced serum concentrations of CRP and pro-inflammatory interleukins (IL-6, IL-7 and IL-18), in addition to enhanced endothelial function and insulin sensitivity, after two years of a Mediterranean diet, rich in EVOO, versus a low-fat diet [14]. Moreover, nutritionally relevant concentrations of EVOO had additive effects in preventing adiponectin downregulation in inflamed human adipocytes through an attenuation of JNK-mediated peroxisome proliferatoractivated receptor suppression [15]. On the other hand, 12 weeks of EVOO consumption increased the antiinflammatory effect of HDL and reduced anti-atherogenic activity in healthy subjects [16].…”

Hydroxytyrosol in the Prevention of the Metabolic Syndrome and Related Disorders

“…Considering that leptin, a well-known protein acting on satiety and having inflammatory property, HT was shown to lower leptin level in mice thus suggesting that could act as a starving and anti-inflammatory agent (0.03% × 8 weeks and 50 mg/kg/day × 17 weeks) [63,65] and attenuate TNF-α and IL-1β expression in animal model [125,126]. In vitro, HT has been reported to increase adiponectin expression and secretion in the presence of TNF-α (1 to 20 µM) [127], reduce iNOS, cyclooxygenase-2 and TNF-α expressions (25 to 100 µM) [128], reduce nuclear factor-κB (NF-κB) binding activity (50 and 100 µM) [129] and, interestingly, increase iκBα expression, an inhibitor of NF-κB binding activity [129]. Moreover, a reduction of metalloproteinase-9 activity and secretion (1 and 10 µM) [130] and a reduction of prostaglandin E 2 secretion and expression were found (1 and 10 µM) [130].…”