Department of Pediatrics, Division of Endocrinology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Aging (Albany NY). 2020 Jan 26;12(2):1725-1746. doi: 10.18632/aging.102709.
Aging, like obesity, is associated with metabolic and inflammatory alterations within adipose tissue in older individuals. Younger females are protected from adipose inflammation, but older post-menopausal females exhibit exaggerated visceral adiposity correlated with increased disease risk. Obesity accelerates the onset and progression of age-associated diseases, but it is unclear if aging and obesity drive adipose tissue dysfunction in a sexually dimorphic fashion. We investigated adipose tissue metabolism and inflammation in a diet-induced obesity model in young and old mice. We identified age related sex differences in adipose tissue macrophages (ATMs), fibrosis and lipid metabolism in male and female visceral fat depot (GWAT). Although aging normalized body weights between the sexes, females remained protected from proinflammatory ATMs and stimulated lipolysis failed to adversely affect the inflammatory state even with obesity. Older obese males had augmented CD11c ATMs and higher insulin levels, while females showed increased visceral adiposity and exaggerated and expression. Obesity in aging demonstrated similar expression of GWAT and in both sexes. Our studies suggest that even with aging, female GWAT shows an attenuated inflammatory response compared to males due to an efficient oxidative metabolism combined with an active tissue remodeling state.
衰老和肥胖一样，会导致老年人脂肪组织内发生代谢和炎症改变。年轻女性对脂肪炎症有一定的保护作用，但绝经后老年女性表现出明显的内脏脂肪堆积，与疾病风险增加相关。肥胖会加速与年龄相关疾病的发生和发展，但目前尚不清楚衰老和肥胖是否会以性别二态的方式导致脂肪组织功能障碍。我们在年轻和老年小鼠的饮食诱导肥胖模型中研究了脂肪组织代谢和炎症。我们发现，雄性和雌性内脏脂肪组织（GWAT）中的脂肪组织巨噬细胞（ATMs）、纤维化和脂质代谢存在与年龄相关的性别差异。尽管衰老使两性之间的体重正常化，但女性仍然免受促炎 ATMs 的影响，并且即使肥胖，刺激脂肪分解也不会对炎症状态产生不利影响。肥胖的老年雄性小鼠具有更多的 CD11c ATMs 和更高的胰岛素水平，而雌性小鼠则表现出更高的内脏脂肪量和更明显的 和 表达。衰老相关肥胖在两性中表现出相似的 GWAT 和 表达。我们的研究表明，即使在衰老的情况下，由于高效的氧化代谢和活跃的组织重塑状态，女性 GWAT 仍表现出比男性更弱的炎症反应。
