Clodronate liposomes improve metabolic profile and reduce visceral adipose macrophage content in diet-induced obese mice.
Clodronate liposomes improve metabolic profile and reduce visceral adipose macrophage content in diet-induced obese mice.
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DOI：
10.1371/journal.pone.0024358
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Feng B;Jiao P;Nie Y;Kim T;Jun D;van Rooijen N;Yang Z;Xu H
肥胖相关的脂肪炎症一直被认为是导致胰岛素抵抗和2型糖尿病的原因之一。肥胖动物和人类脂肪组织中的巨噬细胞是炎性细胞因子的重要来源。氯屈膦酸脂质体可通过诱导细胞凋亡来抑制巨噬细胞的生长。在这项研究中，我们旨在确定在饮食诱导肥胖(DIO)小鼠中，腹腔注射氯屈膦酸盐脂质体是否会对系统的葡萄糖稳态/胰岛素敏感性有任何有益的影响，以及内脏脂肪组织中的巨噬细胞含量是否会减少。用氯屈膦酸脂质体耗尽瘦小鼠和DIO小鼠的巨噬细胞。检测内脏脂肪组织中巨噬细胞含量、代谢参数、葡萄糖和胰岛素耐量、脂肪和肝脏组织学、脂肪因子和细胞因子的产生。还进行了高胰岛素-正常血糖钳夹试验，以评估全身胰岛素敏感性。腹腔注射氯屈膦酸盐脂质体可显著降低DIO小鼠的血糖和胰岛素水平。通过腹腔注射氯屈膦酸盐脂质体(IP)，瘦小鼠和DIO鼠的全身糖耐量和胰岛素敏感性均有轻微改善。使用氯屈膦酸脂质体治疗的DIO小鼠，肝脏骨质疏松症显著减轻，肝脏葡萄糖输出抑制显著增加。能有效降低DIO小鼠内脏脂肪组织中巨噬细胞的含量，而不影响皮下脂肪组织。有趣的是，胰岛素增敏激素脂联素的水平，包括高分子形式，在循环中显著升高。腹腔注射氯屈膦酸盐脂质体可减少内脏脂肪组织巨噬细胞，改善DIO小鼠全身葡萄糖稳态和胰岛素敏感性，这可能部分归因于脂联素水平的增加。
Obesity-related adipose inflammation has been thought to be a causal factor for the development of insulin resistance and type 2 diabetes. Infiltrated macrophages in adipose tissue of obese animals and humans are an important source for inflammatory cytokines. Clodronate liposomes can ablate macrophages by inducing apoptosis. In this study, we aim to determine whether peritoneal injection of clodronate liposomes has any beneficial effect on systemic glucose homeostasis/insulin sensitivity and whether macrophage content in visceral adipose tissue will be reduced in diet-induced obese (DIO) mice. Clodronate liposomes were used to deplete macrophages in lean and DIO mice. Macrophage content in visceral adipose tissue, metabolic parameters, glucose and insulin tolerance, adipose and liver histology, adipokine and cytokine production were examined. Hyperinsulinemic-euglycemic clamp study was also performed to assess systemic insulin sensitivity. Peritoneal injection of clodronate liposomes significantly reduced blood glucose and insulin levels in DIO mice. Systemic glucose tolerance and insulin sensitivity were mildly improved in both lean and DIO mice treated with clodronate liposomes by intraperitoneal (ip) injection. Hepatosteatosis was dramatically alleviated and suppression of hepatic glucose output was markedly increased in DIO mice treated with clodronate liposomes. Macrophage content in visceral adipose tissue of DIO mice was effectively decreased without affecting subcutaneous adipose tissue. Interestingly, levels of insulin sensitizing hormone adiponectin, including the high molecular weight form, were significantly elevated in circulation. Intraperitoneal injection of clodronate liposomes reduces visceral adipose tissue macrophages, improves systemic glucose homeostasis and insulin sensitivity in DIO mice, which can be partially attributable to increased adiponectin levels.
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