Proinflammatory effects of arachidonic acid in a lipopolysaccharide-induced inflammatory microenvironment in 3T3-L1 adipocytes in vitro

Abstract

Long-chain n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have known anti-inflammatory effects, including the modulation of adipose tissue-derived inflammatory mediators (i.e., adipokines) implicated in obesity-related pathologies, such as insulin resistance. Less is known about the effects of plant-derived n-3 PUFA, α-linolenic acid (ALA, 18:3n-3) and stearidonic acid (SDA 18:4n-3), or n-6 PUFA linoleic acid (LA, 18:2n-6) and arachidonic acid (AA, 20:4n-6), especially in combination with an inflammatory stimulus, such as lipopolysaccharide (LPS), at a dose intended to mimic obesity-associated low-grade inflammation. To study this, 3T3-L1 adipocytes were incubated with 100 μmol/L of various n-3 or n-6 PUFA with or without 10 ng/mL LPS for up to 24 h. AA in the presence of LPS synergistically increased (p < 0.05) pro-inflammatory monocyte chemoattractant protein-1 (MCP)-1 and interleukin (IL)-6 secretion and gene expression, as well as COX-2 and TLR2 gene expression at 6 and/or 24 h, suggesting their potential roles in the synergistic effects of AA and LPS. Plant-derived fatty acids ALA, SDA, and LA did not differentially affect adipokine gene expression or secretion, whereas LPS-induced pro-inflammatory IL-1β expression and MCP-1 secretion was decreased (p< 0.05) by EPA, DHA, and/or EPA+DHA (50 μmol/L each) compared with LPS alone. Only DHA increased (p < 0.05) gene expression of the n-3 PUFA receptor GPR120 and simultaneously decreased LPS-induced nuclear factor-κB activation compared with control. Our findings emphasize that specific fatty acids within the n-3 or n-6 PUFA class warrant consideration in the development of nutritional strategies to improve obesity-associated inflammation.

The role of pericardial adipose tissue in the heart of obese minipigs

“…Arachidonic acid promotes the differentiation of mesenchymal stem cells into adipocytes and increases lipogenesis. 30 Under normal physiological conditions, heart fat (PAT) has metabolic, thermogenic and mechanic properties to maintain the normal functions of the heart, 6 whereas under HFD stimulus, as in this study, more LA was converted into AA, thus causing more AA accumulation and an LA deficit in PAT. 28,29 Under the inflammatory stimulus, AA further induces the secretion of adipose tissue-derived inflammatory mediators, such as MCP-1 and IL6.…”

“…28,29 Under the inflammatory stimulus, AA further induces the secretion of adipose tissue-derived inflammatory mediators, such as MCP-1 and IL6. 30 Under normal physiological conditions, heart fat (PAT) has metabolic, thermogenic and mechanic properties to maintain the normal functions of the heart, 6 whereas under HFD stimulus, as in this study, more LA was converted into AA, thus causing more AA accumulation and an LA deficit in PAT. Taken together, the changes in fatty acid composition by HFD potentially induced proinflammation and insulin resistance, inhibited metabolic activity, and suppressed the formation of the brite-like adipocyte, thus causing local adverse effects on heart functions.…”

Screening the active compounds of Phellodendri Amurensis cortex for treating prostate cancer by high-throughput chinmedomics

“…Arachidonic acid, Thromboxane, 16(R)-HETE, Prostaglandin A1, Prostaglandin A2, and 8-Isoprostane are involved in arachidonic acid metabolism. Arachidonic acid and its metabolites, as the main inflammatory substances, are taking part in the process of immune and inflammatory actions6061. Thromboxane could promote cancer cell proliferation through enhancing the activity of cell mitosis6263.…”

Forskolin Inhibits Lipopolysaccharide-Induced Modulation of MCP-1 and GPR120 in 3T3-L1 Adipocytes through an Inhibition of NFκB

“…These data are particularly interesting as, in a macrophage cell line, DHA (a GPR120 agonist) antagonizes the proinflammatory effects of TNF- α and LPS and requires the presence of GPR120 to counteract the proinflammatory actions of LPS on cytokines' gene expression and protein secretion [14]. In the presence of LPS, DHA significantly decreased MCP-1 mRNA level but increased both β -Arrestin 2 and GPR120 mRNA levels [38]. The inhibitory effects of DHA on LPS-(TLR-4)-induced activation of NFkB activity might be mediated by a GPR120- β -Arrestin 2-dependent mechanism [14].…”