Talbot Nicola A, Wheeler-Jones Caroline P, Cleasby Mark E
Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK.
Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK.
Mol Cell Endocrinol. 2014 Aug 5;393(1-2):129-42. doi: 10.1016/j.mce.2014.06.010. Epub 2014 Jun 26.
Obesity and saturated fatty acid (SFA) treatment are both associated with skeletal muscle insulin resistance (IR) and increased macrophage infiltration. However, the relative effects of SFA and unsaturated fatty acid (UFA)-activated macrophages on muscle are unknown. Here, macrophages were treated with palmitic acid, palmitoleic acid or both and the effects of the conditioned medium (CM) on C2C12 myotubes investigated. CM from palmitic acid-treated J774s (palm-mac-CM) impaired insulin signalling and insulin-stimulated glycogen synthesis, reduced Inhibitor κBα and increased phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase in myotubes. p38 MAPK inhibition or siRNA partially ameliorated these defects, as did addition of tumour necrosis factor-α blocking antibody to the CM. Macrophages incubated with both FAs generated CM that did not induce IR, while palmitoleic acid-mac-CM alone was insulin sensitising. Thus UFAs may improve muscle insulin sensitivity and counteract SFA-mediated IR through an effect on macrophage activation.
肥胖和饱和脂肪酸（SFA）处理均与骨骼肌胰岛素抵抗（IR）及巨噬细胞浸润增加有关。然而，SFA和不饱和脂肪酸（UFA）激活的巨噬细胞对肌肉的相对影响尚不清楚。在此，用棕榈酸、棕榈油酸或两者处理巨噬细胞，并研究条件培养基（CM）对C2C12肌管的影响。来自棕榈酸处理的J774细胞的CM（棕榈酸-巨噬细胞-CM）损害胰岛素信号传导和胰岛素刺激的糖原合成，降低抑制蛋白κBα，并增加肌管中p38丝裂原活化蛋白激酶（MAPK）和c-Jun氨基末端激酶的磷酸化。p38 MAPK抑制或小干扰RNA（siRNA）部分改善了这些缺陷，向CM中添加肿瘤坏死因子-α阻断抗体也有同样效果。用两种脂肪酸孵育的巨噬细胞产生的CM不诱导IR，而单独的棕榈油酸-巨噬细胞-CM具有胰岛素增敏作用。因此，UFA可能通过对巨噬细胞激活的影响来改善肌肉胰岛素敏感性并抵消SFA介导的IR。
