PDF(Pubmed)
Abstract：
BACKGROUND: Female mice are more resistant to obesogenic effects of a high-fat diet (HFD), compared to male mice. Although the underlying mechanisms are poorly understood, sex hormones seem to play an important role. Interestingly, the activity of the oestrogen receptor-α (ERα) is affected by the calcium-sensing-receptor (CaSR). Therefore, we investigated sex-differences upon diet-induced obesity and the role of adipocyte-specific CaSR herein.
METHODS: Adipocyte-specific Casr deficient mice (AdipoqCre+Casrflox) and control mice (Casrflox) were injected with AAV8-PCSK9 to make them prone to develop atherosclerosis and fed an obesity-inducing diet for 12 weeks.
RESULTS: Female mice have lower visceral white adipose tissue (vWAT) mass compared to male mice, while this sex-difference is abolished upon adipocyte-specific Casr deficiency. Furthermore, while females showed elevated levels of inflammatory cytokines and CD3+CD8+ T cell accumulation in vWAT, compared to males, adipocyte-specific Casr deficiency abrogated this sex-phenotype and demonstrated an inhibition of inflammatory signalling pathways. The expression of Erα, as well as associated genes involved in adipocyte differentiation, was increased in female mice in a mostly adipocyte-specific Casr dependent manner. Interestingly, circulating lipid levels were reduced in female compared to male mice, which correlated with decreased atherosclerotic plaque formation. These systemic effects were abrogated upon adipocyte-specific Casr deficiency.
CONCLUSIONS: Our findings indicate that female mice show a more pronounced vWAT dysfunction compared to males upon obesity. This sex effect is abolished upon adipocyte-specific Casr deficiency. In contrast, females show diminished atherosclerotic plaque formation compared to males, an effect that was abrogated by adipocyte-specific Casr deficiency.
BACKGROUND: This work was supported by a grant from the Interdisciplinary Center for Clinical Research within the faculty of Medicine at the RWTH Aachen University, by the Corona Foundation, by the Deutsche Forschungsgemeinschaft (DFG), the BMBF and Free State of Bavaria and the DZHK.
METHODS: Adipocyte-specific Casr deficient mice (AdipoqCre+Casrflox) and control mice (Casrflox) were injected with AAV8-PCSK9 to make them prone to develop atherosclerosis and fed an obesity-inducing diet for 12 weeks.
RESULTS: Female mice have lower visceral white adipose tissue (vWAT) mass compared to male mice, while this sex-difference is abolished upon adipocyte-specific Casr deficiency. Furthermore, while females showed elevated levels of inflammatory cytokines and CD3+CD8+ T cell accumulation in vWAT, compared to males, adipocyte-specific Casr deficiency abrogated this sex-phenotype and demonstrated an inhibition of inflammatory signalling pathways. The expression of Erα, as well as associated genes involved in adipocyte differentiation, was increased in female mice in a mostly adipocyte-specific Casr dependent manner. Interestingly, circulating lipid levels were reduced in female compared to male mice, which correlated with decreased atherosclerotic plaque formation. These systemic effects were abrogated upon adipocyte-specific Casr deficiency.
CONCLUSIONS: Our findings indicate that female mice show a more pronounced vWAT dysfunction compared to males upon obesity. This sex effect is abolished upon adipocyte-specific Casr deficiency. In contrast, females show diminished atherosclerotic plaque formation compared to males, an effect that was abrogated by adipocyte-specific Casr deficiency.
BACKGROUND: This work was supported by a grant from the Interdisciplinary Center for Clinical Research within the faculty of Medicine at the RWTH Aachen University, by the Corona Foundation, by the Deutsche Forschungsgemeinschaft (DFG), the BMBF and Free State of Bavaria and the DZHK.
摘要：
背景：雌性小鼠对高脂饮食（HFD）的致胖作用更具抵抗力，与雄性小鼠相比。尽管人们对潜在的机制知之甚少，性激素似乎起着重要作用。有趣的是,雌激素受体α（ERα）的活性受钙敏感受体（CaSR）的影响。因此,我们在此研究了饮食诱导的肥胖的性别差异以及脂肪细胞特异性CaSR的作用.
方法：向脂肪细胞特异性Casr缺陷小鼠（AdipoqCre+Casrflox）和对照小鼠（Casrflox）注射AAV8-PCSK9，使它们容易发生动脉粥样硬化，并喂养诱导肥胖的饮食12周。
结果：与雄性小鼠相比，雌性小鼠的内脏白色脂肪组织（vWAT）质量较低，而这种性别差异在脂肪细胞特异性Casr缺乏症后消失。此外，而女性在vWAT中显示出炎性细胞因子和CD3+CD8+T细胞积累水平升高，与男性相比，脂肪细胞特异性Casr缺乏症消除了这种性别表型，并表现出对炎症信号通路的抑制。Erα的表达，以及参与脂肪细胞分化的相关基因，在雌性小鼠中以主要是脂肪细胞特异性Casr依赖性方式增加。有趣的是,与雄性小鼠相比，雌性小鼠的循环脂质水平降低，这与动脉粥样硬化斑块形成减少有关。这些全身性作用在脂肪细胞特异性Casr缺乏时被消除。
结论：我们的发现表明，与肥胖的雄性小鼠相比，雌性小鼠表现出更明显的vWAT功能障碍。这种性别效应在脂肪细胞特异性Casr缺乏时被消除。相比之下,女性与男性相比动脉粥样硬化斑块形成减少，脂肪细胞特异性Casr缺乏症消除了这种效应。
背景：这项工作得到了亚琛工业大学医学院临床研究跨学科中心的资助，Corona基金会,由德国Forschungsgemeinschaft（DFG），巴伐利亚和DZHK的BMBF和自由州。
方法：向脂肪细胞特异性Casr缺陷小鼠（AdipoqCre+Casrflox）和对照小鼠（Casrflox）注射AAV8-PCSK9，使它们容易发生动脉粥样硬化，并喂养诱导肥胖的饮食12周。
结果：与雄性小鼠相比，雌性小鼠的内脏白色脂肪组织（vWAT）质量较低，而这种性别差异在脂肪细胞特异性Casr缺乏症后消失。此外，而女性在vWAT中显示出炎性细胞因子和CD3+CD8+T细胞积累水平升高，与男性相比，脂肪细胞特异性Casr缺乏症消除了这种性别表型，并表现出对炎症信号通路的抑制。Erα的表达，以及参与脂肪细胞分化的相关基因，在雌性小鼠中以主要是脂肪细胞特异性Casr依赖性方式增加。有趣的是,与雄性小鼠相比，雌性小鼠的循环脂质水平降低，这与动脉粥样硬化斑块形成减少有关。这些全身性作用在脂肪细胞特异性Casr缺乏时被消除。
结论：我们的发现表明，与肥胖的雄性小鼠相比，雌性小鼠表现出更明显的vWAT功能障碍。这种性别效应在脂肪细胞特异性Casr缺乏时被消除。相比之下,女性与男性相比动脉粥样硬化斑块形成减少，脂肪细胞特异性Casr缺乏症消除了这种效应。
背景：这项工作得到了亚琛工业大学医学院临床研究跨学科中心的资助，Corona基金会,由德国Forschungsgemeinschaft（DFG），巴伐利亚和DZHK的BMBF和自由州。
