Romero Maria, Gelsomini Andrew, Miller Kate, Suresh Dhananjay, Thaller Seth, Frasca Daniela
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, United States.
DeWitt Daughtry Family Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Miami Miller School of Medicine, Miami, FL, United States.
J Nutr. 2025 Feb;155(2):445-452. doi: 10.1016/j.tjnut.2024.10.013. Epub 2024 Oct 9.
Our previous work has shown that senescent B cells accumulate in the human adipose tissue (AT) of people with obesity, where they express transcripts for markers associated with the senescence-associated secretory phenotype (SASP) and secrete multiple inflammatory mediators. These functions of AT-derived B cells are metabolically supported.
To show that Metformin (MET), a widely used hypoglycemic and antidiabetic drug, is able at least in vitro to decrease frequencies, secretory profile, and metabolic requirements of senescent B cells isolated from the AT of people with obesity.
We recruited adult females with obesity (n = 8, age 40 ± 2 y, BMI range: 33-42) undergoing breast reduction surgery, who donated their discarded subcutaneous AT. B cells from stromal vascular fractions isolated after collagenase digestion of the AT were evaluated after in vitro incubation with MET (1 mM × 10 B cells) or with a control medium without MET for the following measures: expression of transcripts for SASP-associated markers (p16 and p21) measured by quantitative polymerase chain reaction (qPCR); secretion of inflammatory cytokines (TNF-α, IL-6, IFN-γ and IL-17A) measured by a Cytometric Bead Array); metabolic characteristics as identified by a glycolytic test and Seahorse technology, and by the expression of transcripts for glucose transporters and metabolic enzymes involved in glucose metabolic pathways, measured by qPCR. To examine differences between MET-treated compared with untreated groups, paired Student's t tests (two-tailed) were employed.
MET in vitro was able to reduce frequencies and numbers of senescent B cells, as identified by staining with β-galactosidase, as well as the secretion of inflammatory cytokines, the expression of transcripts for SASP, and metabolic markers that support intrinsic B cell inflammation.
Our results provide evidence to support the beneficial effects of MET in reducing AT-related inflammation through its effects on senescent B cells.
我们之前的研究表明，衰老的B细胞在肥胖人群的人体脂肪组织（AT）中积累，在那里它们表达与衰老相关分泌表型（SASP）相关标志物的转录本，并分泌多种炎症介质。脂肪组织来源的B细胞的这些功能得到代谢支持。
证明二甲双胍（MET），一种广泛使用的降血糖和抗糖尿病药物，至少在体外能够降低从肥胖人群的脂肪组织中分离出的衰老B细胞的频率、分泌谱和代谢需求。
我们招募了接受乳房缩小手术的肥胖成年女性（n = 8，年龄40 ± 2岁，BMI范围：33 - 42），她们捐赠了废弃的皮下脂肪组织。在脂肪组织经胶原酶消化后从基质血管部分分离出的B细胞，在与MET（1 mM×10个B细胞）或不含MET的对照培养基进行体外孵育后，进行以下测量：通过定量聚合酶链反应（qPCR）测量SASP相关标志物（p16和p21）的转录本表达；通过细胞计数珠阵列测量炎症细胞因子（TNF-α、IL-6、IFN-γ和IL-17A）的分泌；通过糖酵解试验和海马技术以及通过qPCR测量参与葡萄糖代谢途径的葡萄糖转运蛋白和代谢酶的转录本表达来确定代谢特征。为了检验MET处理组与未处理组之间的差异，采用配对学生t检验（双侧）。
体外实验中，MET能够降低衰老B细胞的频率和数量，这通过β-半乳糖苷酶染色得以鉴定，同时还能降低炎症细胞因子的分泌、SASP转录本的表达以及支持内在B细胞炎症的代谢标志物。
我们的结果提供了证据，支持MET通过对衰老B细胞的作用来减少与脂肪组织相关炎症的有益效果。
