Obesogenic Memory Maintains Adipose Tissue Inflammation and Insulin Resistance.
Obesogenic Memory Maintains Adipose Tissue Inflammation and Insulin Resistance.
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DOI：
10.20900/immunometab20200023
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发表时间：
2020-01-01
期刊：
影响因子：
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通讯作者：
Hsueh, Willa A
中科院分区：
文献类型：
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作者：
Blaszczak, Alecia M;Bernier, Matt;Hsueh, Willa A
背景：肥胖的特征是内脏脂肪组织（AT）炎症。免疫抑制调节性T细胞（Tregs）、吞噬性m2样巨噬细胞和先天淋巴样细胞2型（ILC2）控制AT炎症以维持全身胰岛素敏感性，而肥胖中这些细胞的缺失导致AT炎症和胰岛素抵抗（IR）。目的：本研究的目的是确定肥胖后体重减轻是否会纠正AT炎症和全身代谢。结果：在雄性C57/Bl6小鼠高脂肪饮食（HFD）六个月后，附睾AT基质血管分数（SVF）的流动分析显示Tregs减少50%，CD8+ T细胞增加一倍，促炎m1样巨噬细胞增加三倍，ILC2细胞下降80%，与促炎脂肪细胞和巨噬细胞基因表达的变化相关。尽管体重、脂肪和脂肪细胞大小恢复正常，但连续3个月高脂肪饮食（HFD）和3个月低脂肪饮食的小鼠仍比低脂肪饮食的小鼠更具胰岛素抵抗性和葡萄糖耐受性。脂肪细胞、AT Tregs、CD8+ T细胞、ILC2细胞和m1样巨噬细胞都不能随着体重减轻而恢复正常。结论：尽管先前肥胖小鼠的体重和脂肪正常化，持续性AT炎症有助于IR的维持。这些发现强调了预防肥胖的重要性，以避免“肥胖记忆”的后果。
BACKGROUND: Obesity is characterized by visceral adipose tissue (AT) inflammation. Immunosuppressive regulatory T cells (Tregs), phagocytic M2-like macrophages, and innate lymphoid cells type 2 (ILC2) control lean AT inflammation to maintain systemic insulin sensitivity, while the loss of these cells in obesity leads to AT inflammation and insulin resistance (IR).OBJECTIVE: The objective of this study was to determine if weight loss following obesity would correct AT inflammation and systemic metabolism.RESULTS: After six months of high fat diet (HFD) in male C57/Bl6 mice, flow analyses of epidydimal AT stromal vascular fraction (SVF) revealed depleted Tregs by 50%, doubling of CD8+ T cells, tripling of pro-inflammatory M1-like macrophages, and an 80% drop in ILC2 cells associated with changes in pro-inflammatory adipocyte and macrophage gene expression. Despite normalization of body weight, fat, and adipocyte size, mice ingesting 3 months of high-fat diet (HFD) followed by 3 months of chow-diet remained more insulin resistant and glucose intolerant than chow-fed animals. Adipocytes, AT Tregs, CD8+ T cells, ILC2 cells, and M1-like macrophages all failed to normalize with weight loss.CONCLUSIONS: Persistent AT inflammation contributes to the maintenance of IR despite body weight and fat normalization in previously obese mice. These findings highlight the importance of obesity prevention to avoid the consequences of "obesogenic memory."