Imano Natsumi, Shojima Kensaku, Tamaki Kayoko, Shinmura Ken
Department of Bioscience, Kwansei Gakuin University, Sanda, Japan.
Department of General Internal Medicine, Hyogo Medical University School of Medicine, Nishinomiya, Japan.
Am J Physiol Heart Circ Physiol. 2023 May 1;324(5):H662-H674. doi: 10.1152/ajpheart.00469.2022. Epub 2023 Mar 17.
It remains unclear whether sex differences exist during the development of visceral adipose tissue (VAT) inflammation associated with obesity. The purpose of this study was to clarify sex differences in the occurrence of senescence-related T cells (CD44 PD-1 CD4), which play a key role in the progression of VAT inflammation associated with high-fat diet (HFD)-induced obesity. : C57BL/6N mice were fed either a control diet (HFC) or HFD for 5 wk. The area under the curve of the oral glucose-tolerance test (oGTT) was maximal at 15 wk in HFD-fed males and at 21 wk in females. At 17 wk, VAT weights were similar, but an increase in the number of macrophages in the VAT was observed only in HFD-fed males. In addition, the numbers of regulatory and senescence-related T cells were consistently higher in males than in females. and : 6-wk-old female mice were randomly divided into sham operation and bilateral ovariectomy (OVX) groups and fed either an HFC or HFD from 7 wk. OVX mice were subjected to 17β-estradiol releasing or placebo pellet implantation and fed an HFC. Body and VAT weights were higher in the OVX group than in the sham. The number of macrophages did not change in the OVX group with either diet. HFC-fed OVX mice exhibited high senescence-related T cells in the VAT, resembling HFC-fed male mice. This change was abolished by 17β-estradiol replacement. Thus, we demonstrated different accumulation patterns of VAT immune cells between the sexes, revealing a role for estrogen in the appearance of senescence-related T cells. The accumulation pattern of adipose tissue differs between the sexes; however, it is unclear whether sex differences exist during the development of adipose tissue inflammation and whether estrogen plays a role. We demonstrated sex differences in immune cells' subpopulation of visceral adipose tissue. The proinflammatory environment appeared earlier in males than in females. In addition, our results suggest that estrogen plays a role in visceral adipose tissue inflammation, particularly by regulating the appearance of senescence-related T cells.
与肥胖相关的内脏脂肪组织（VAT）炎症发展过程中是否存在性别差异仍不清楚。本研究的目的是阐明衰老相关T细胞（CD44 PD-1 CD4）出现的性别差异，这些细胞在高脂饮食（HFD）诱导的肥胖相关VAT炎症进展中起关键作用。：将C57BL/6N小鼠喂食对照饮食（HFC）或HFD 5周。口服葡萄糖耐量试验（oGTT）曲线下面积在喂食HFD的雄性小鼠中15周时最大，在雌性小鼠中21周时最大。在17周时，VAT重量相似，但仅在喂食HFD的雄性小鼠中观察到VAT中巨噬细胞数量增加。此外，雄性小鼠中调节性和衰老相关T细胞的数量始终高于雌性。和：将6周龄雌性小鼠随机分为假手术组和双侧卵巢切除术（OVX）组，并从7周起喂食HFC或HFD。对OVX小鼠进行17β-雌二醇释放或安慰剂颗粒植入，并喂食HFC。OVX组的体重和VAT重量高于假手术组。无论哪种饮食，OVX组中的巨噬细胞数量均未改变。喂食HFC的OVX小鼠在VAT中表现出高衰老相关T细胞，类似于喂食HFC的雄性小鼠。这种变化被17β-雌二醇替代消除。因此，我们证明了两性之间VAT免疫细胞的不同积累模式，揭示了雌激素在衰老相关T细胞出现中的作用。脂肪组织的积累模式在两性之间有所不同；然而，尚不清楚在脂肪组织炎症发展过程中是否存在性别差异以及雌激素是否起作用。我们证明了内脏脂肪组织免疫细胞亚群存在性别差异。促炎环境在雄性中比在雌性中出现得更早。此外，我们的结果表明雌激素在内脏脂肪组织炎症中起作用，特别是通过调节衰老相关T细胞的出现。
