The calcium-sensing-receptor in adipocytes is a driver of adipose tissue inflammation and thereby seems to exacerbate atherosclerosis development in an obesity mouse model
Atherosclerosis(2023)
摘要
Background and Aims: Obesity is a main risk factor of atherosclerosis, characterized by excessive deposition of visceral white adipose tissue (vWAT). In obese humans increased calcium sensitivity may result in increased activation of the calcium-sensing-receptor (CaSR), thereby driving disease development. Genome wide association studies already demonstrated a correlation between diabetes, obesity and genetic variants of CaSR. Furthermore, recent in-vitro studies demonstrated that CaSR plays an important role in adipocyte-driven metabolic processes. Nevertheless, the exact role of adipocyte CaSR in-vivoremains elusive. Methods: Adipocyte-specific CaSR-deficient mice (AdipoqCreCaSRfloxAAV8-PCSK9) were fed an obesity diet (60% fat) for 12 weeks in order to provide new in-vivoinsights into the function of adipocyte CaSR in AT inflammation and atherosclerosis development. Lipid levels were measured in the plasma, vWAT and liver and inflammatory cytokine in the plasma. Plaque size was evaluated in the aortic root. Results: Adipocyte-specific CaSR deficiency in female mice led to a relative increase in vWAT weight. Interestingly, while circulating and liver lipid levels were elevated in female mice, no changes were observed in the lipid content of vWAT. However, the absence of adipocyte-CaSR resulted in a sharp decrease of the inflammatory cytokines IL-6, TNF-α and CCL2 in vWAT in both genders. Furthermore and in line with this anti-inflammatory AT phenotype, a trend towards less atherosclerotic plaque formation could be observed in adipocyte-specific CaSR deficient mice. Conclusions: In conclusion, our findings indicate that adipocyte-specific CaSR increases inflammatory processes in AT in a mouse model of obesity, which seems to overrule effects and lipid levels and thereby exacerbates atherosclerosis development.
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关键词
adipose tissue inflammation,adipocytes,atherosclerosis development,obesity,calcium-sensing-receptor
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