OBJECTIVE: Obesity correlates with increased production of adipocyte-derived cytokines, which may contribute to a chronic subclinical inflammation seen in obese individuals. This study evaluated the ability of specific fatty acids to modulate production of the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), and the anti-inflammatory cytokine, interleukin-10 (IL-10), in murine 3T3-L1 adipocytes. Effects on nuclear factor-kappaB (NF-kappaB), a key transcriptional activator of the inflammatory cascade, and suppressor of cytokine signaling 3 (SOCS-3), a negative regulator of cytokine signaling, were also determined. METHODS AND PROCEDURES: Adipocytes were incubated for 24 and 48 h with and without 50 or 500 micromol/l of palmitic acid, oleic acid, or docosahexaenoic acid, (DHA). Effects on gene expression and protein secretion of TNF-alpha and IL-10 were determined using real-time PCR and a murine multipex RIA kit. SOCS-3 expression was determined by northern blotting and NF-kappaB binding activity was assessed using a commercially available assay. RESULTS: Adipocytes treated for 24 h with palmitic acid exhibited a 70% increase in TNF-alpha production and up to a 75% decrease in IL-10 production, relative to untreated cells. In contrast, DHA treatment had no effect on TNF-alpha, but increased IL-10 production twofold. No effect of oleic acid was seen on either TNF-alpha or IL-10 production. Similar results were obtained during a 48-h incubation. Furthermore, NF-kappaB DNA-binding activity increased fourfold in response to palmitic acid and decreased 60% in response to DHA. Expression of SOCS-3 increased twofold in DHA-treated cells. DISCUSSION: In aggregate, these results suggest that dietary fatty acids act directly on adipocytes to modulate cytokine production. As circulating fatty acids levels are chronically elevated in obese individuals, this effect may account in part for obesity-associated inflammation.
OBJECTIVE:Obesity correlates with increased production of adipocyte-derived cytokines, which may contribute to a chronic subclinical inflammation seen in obese individuals. This study evaluated the ability of specific fatty acids to modulate production of the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), and the anti-inflammatory cytokine, interleukin-10 (IL-10), in murine 3T3-L1 adipocytes. Effects on nuclear factor-kappaB (NF-kappaB), a key transcriptional activator of the inflammatory cascade, and suppressor of cytokine signaling 3 (SOCS-3), a negative regulator of cytokine signaling, were also determined. METHODS AND PROCEDURES: Adipocytes were incubated for 24 and 48 h with and without 50 or 500 micromol/l of palmitic acid, oleic acid, or docosahexaenoic acid, (DHA). Effects on gene expression and protein secretion of TNF-alpha and IL-10 were determined using real-time PCR and a murine multipex RIA kit. SOCS-3 expression was determined by northern blotting and NF-kappaB binding activity was assessed using a commercially available assay. RESULTS: Adipocytes treated for 24 h with palmitic acid exhibited a 70% increase in TNF-alpha production and up to a 75% decrease in IL-10 production, relative to untreated cells. In contrast, DHA treatment had no effect on TNF-alpha, but increased IL-10 production twofold. No effect of oleic acid was seen on either TNF-alpha or IL-10 production. Similar results were obtained during a 48-h incubation. Furthermore, NF-kappaB DNA-binding activity increased fourfold in response to palmitic acid and decreased 60% in response to DHA. Expression of SOCS-3 increased twofold in DHA-treated cells. DISCUSSION: In aggregate, these results suggest that dietary fatty acids act directly on adipocytes to modulate cytokine production. As circulating fatty acids levels are chronically elevated in obese individuals, this effect may account in part for obesity-associated inflammation.
Authors: B Emanuelli; P Peraldi; C Filloux; C Chavey; K Freidinger; D J Hilton; G S Hotamisligil; E Van Obberghen Journal: J Biol Chem Date: 2001-10-16 Impact factor: 5.157
Authors: Jong In Kim; Jin Young Huh; Jee Hyung Sohn; Sung Sik Choe; Yun Sok Lee; Chun Yan Lim; Ala Jo; Seung Bum Park; Weiping Han; Jae Bum Kim Journal: Mol Cell Biol Date: 2015-03-02 Impact factor: 4.272
Authors: Saraswoti Khadge; Geoffrey M Thiele; John Graham Sharp; Timothy R McGuire; Lynell W Klassen; Paul N Black; Concetta C DiRusso; Leah Cook; James E Talmadge Journal: Clin Exp Metastasis Date: 2018-10-16 Impact factor: 5.150