Department of Pediatrics, Rhode Island Hospital and Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
Obesity (Silver Spring). 2013 Sep;21(9):1843-9. doi: 10.1002/oby.20329. Epub 2013 May 25.
Free fatty acids (FFAs) are increased in visceral fat and contribute to insulin resistance through multiple mechanisms, including c-Jun N-terminal kinase (JNK) activation and expression of TNFα. Given that insulin-like growth factor-1 (IGF-1)-mediated proliferation is impaired in omental compared to subcutaneous (SC) preadipocytes, we investigated IGF-I anti-inflammatory action in preadipocytes from SC and omental adipose tissue.
Preadipocytes isolated from abdominal SC and omental fat of obese subjects were studied in primary culture. Cells were exposed to FFAs with or without IGF-I pretreatment followed by analysis of cytokine expression and JNK phosphorylation. Lentivirus infection was used to express a constitutively active AKT (myr-AKT) in omental preadipocytes.
FFAs increased the expression of tumor necrosis factor (TNF)α, interleukin (IL)-6, and monocyte chemotactic protein (MCP)-1 in SC and omental preadipocytes. IGF-I pretreatment reduced FFA-induced JNK1 phosphorylation and TNFα expression in SC but not omental preadipocytes. Treatment with the JNK1/2 inhibitor SP600125 reduced FFA-induced expression of TNFα. FFAs and MALP-2, a specific TLR2/6 ligand, but not specific ligands for TLR4 and TLR1/2, increased JNK1 phosphorylation. IGF-I completely inhibited MALP-2-stimulated phosphorylation of JNK1. Expression of myr-AKT in omental preadipocytes inhibited FFA-stimulated JNK1 phosphorylation.
IGF-I attenuated FFA-induced JNK1 phosphorylation and TNFα expression through activation of AKT in human subcutaneous but not omental preadipocytes.
游离脂肪酸（FFAs）在内脏脂肪中增加，并通过多种机制导致胰岛素抵抗，包括 c-Jun N 末端激酶（JNK）的激活和 TNFα 的表达。鉴于与皮下（SC）前体脂肪细胞相比，胰岛素样生长因子-1（IGF-1）介导的增殖在网膜前体脂肪细胞中受损，我们研究了 SC 和网膜脂肪组织前体脂肪细胞中 IGF-1 的抗炎作用。
从肥胖受试者的腹部 SC 和网膜脂肪中分离前体脂肪细胞，进行原代培养。细胞暴露于 FFAs 中，或在 IGF-I 预处理后再暴露于 FFAs 中，然后分析细胞因子表达和 JNK 磷酸化。使用慢病毒感染在网膜前体脂肪细胞中表达组成型激活 AKT（myr-AKT）。
FFAs 增加了 SC 和网膜前体脂肪细胞中肿瘤坏死因子（TNF）α、白细胞介素（IL）-6 和单核细胞趋化蛋白（MCP）-1 的表达。IGF-I 预处理可减少 SC 但不减少网膜前体脂肪细胞中 FFA 诱导的 JNK1 磷酸化和 TNFα 表达。使用 JNK1/2 抑制剂 SP600125 可减少 FFA 诱导的 TNFα 表达。FFAs 和 MALP-2（一种特定的 TLR2/6 配体），而不是 TLR4 和 TLR1/2 的特异性配体，可增加 JNK1 磷酸化。IGF-I 可完全抑制 MALP-2 刺激的 JNK1 磷酸化。在网膜前体脂肪细胞中表达 myr-AKT 可抑制 FFA 刺激的 JNK1 磷酸化。
IGF-I 通过在人类 SC 前体脂肪细胞中激活 AKT 来减轻 FFA 诱导的 JNK1 磷酸化和 TNFα 表达，但不能减轻网膜前体脂肪细胞中的这种作用。
