Anti‐inflammatory Effect of Palmitoylethanolamide on Human Adipocytes

Abstract

Obesity leads to the appearance of an inflammatory process, which can be initiated even with a moderate weight gain. Palmitoylethanolamide (PEA) is an endogenous lipid, secreted by human adipocytes, that possesses numerous anti‐inflammatory properties. The main purpose of this study was to investigate the anti‐inflammatory effect of PEA on human adipocytes, as well as in a murine model. The production of tumor necrosis factor–α (TNF‐α) by lipopolysaccharide (LPS)‐treated human subcutaneous adipocytes in primary culture and CF‐1 mice was investigated by enzyme‐linked immunosorbent assay. The effects of PEA on adipocyte TNF‐α secretion were explored as well as some suspected PEA anti‐inflammatory pathways: nuclear factor–κB (NF‐κB) pathway, peroxisome proliferator‐activated receptor–α (PPAR‐α) gene expression, and TNF‐α‐converting enzyme (TACE) activity. The effects of PEA on the TNF‐α serum concentration in intraperitoneally LPS‐treated mice were also studied. We demonstrate that the LPS induced secretion of TNF‐α by human adipocytes is inhibited by PEA. This action is neither linked to a reduction in TNF‐α gene transcription nor to the inhibition of TACE activity. Moreover, PPAR‐α is not implicated in this anti‐inflammatory activity. Lastly, PEA exhibits a wide‐reaching anti‐inflammatory action as the molecule is able to completely inhibit the strong increase in TNF‐α levels in the serum of mice treated with high doses of LPS. In view of its virtual lack of toxicity, PEA might become a potentially interesting candidate molecule in the prevention of obesity‐associated insulin resistance.

Selective cannabinoid-1 receptor blockade benefits fatty acid and triglyceride metabolism significantly in weight-stable nonhuman primates

“…At baseline, plasma AEA concentrations were elevated in those animals with higher fasting insulin concentrations, whereas after treatment, higher AEA concentrations were associated with lower glucose disposal rates (P Ͻ 0.05). Furthermore, posttreatment, higher concentrations of SubQ and VAT OEA and PEA were tightly associated (r Ͼ 0.75) with greater amounts of adipose mass, a finding similar to those of Guardado-Mendoza et al (27), Horeau et al (30), and Matias et al (37), who showed that PEA is the ethanolamide secreted in the highest concentration from human primary adipocytes in culture. In line with the ethanolamides' role in metabolic dysfunction, baboon VAT OEA and PEA concentrations were associated with higher fed-state concentrations of intestinal lipoproteins in plasma (apoB48 concentrations) and lower HDL cholesterol concentrations (Fig.…”

N-Stearoylethanolamine suppresses the pro-inflammatory cytokines production by inhibition of NF-κB translocation

“…However, the earlier data presented no effect of NPE on the IL-6 secretion and NF-B translocation in the human adipocytes [15]. Moreover, later results showed the inhibition by NPE of the LPS-induced secretion of TNF-␣ in the human adipocytes that was not associated with PPAR␣ activation [16]. Unfortunately, now there is no information about the effect of NPE on cytokines synthesis in activated macrophages.…”

Pharmacological inhibition of endocannabinoid degradation modulates the expression of inflammatory mediators in the hypothalamus following an immunological stressor

“…Indeed, it is possible that the effects of OEA and/or PEA may have counteracted the effects of AEA on LPS-induced TNFα levels in the periphery. For example, PEA is known to elicit potent anti-inflammatory effects, including inhibition of LPS-induced increases in plasma TNFα levels (Berdyshev et al, 1998;Hoareau et al, 2009) Cytokines within the hypothalamus have been shown to be responsible for many aspects of the sickness response following endotoxin administration (for reviews see (Beishuizen and Thijs, 2003;Conti et al, 2004;Dantzer, 2009)). For example, IL-1β has been shown to mediate fever (Murakami et al, 1990) and hypophagia (Kent et al, 1994) in response to LPS, effects which can be attenuated by AEA (Hollis et al, 2011).…”