Diebel Mark E, Diebel Lawrence N, Liberati David M
From the Marian and Michael Ilitch Department of Surgery (M.E.D., L.N.D., D.M.L.), Wayne State University, Detroit, Michigan.
J Trauma Acute Care Surg. 2016 Dec;81(6):1028-1034. doi: 10.1097/TA.0000000000001170.
Obesity is a chronic low-grade inflammatory condition associated with the elaboration of proinflammatory cytokines and adipokines from adipose tissue. Gender dimorphism (in part due to sex hormones) has been identified after injury and hemorrhagic shock. We hypothesized that the sex hormones estrogen (E2) and testosterone (DHT) have disparate effects on inflammatory mediator production from adipose tissue under stress conditions. This was studied in an in vitro model.
Mature adipocytes differentiated from adipose-derived stem cells were cocultured (2:1) with macrophages (RAW 264.7) and subjected to hypoxia/reoxygenation (H/R) and/or incubation with physiologic (10 μM) or stress (10 μM) concentrations of epinephrine (epi). Estrogen or DHT was added in a range of physiologic concentrations, and culture supernatants were obtained 12 hours after incubation, and tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and adiponectin levels were measured by enzyme-linked immunosorbent assay.
Basal TNF-α and IL-6 release from cocultures was significantly increased in response to epi and/or H/R conditions. Estrogen decreased cytokine release to basal levels, whereas DHT had no effect. Of note, varying the concentration of epi had no effect on cytokine release. Basal levels of adiponectin release were significantly decreased in response to epi and/or H/R conditions. Estrogen exposure returned adiponectin levels to basal levels, whereas DHT had no effect. The inverse of this relationship was observed in regard to the sex hormones effect on leptin release. Estrogen returned leptin release to basal levels, whereas DHT had no effect.
Stress levels of epi and H/R increased proinflammatory cytokine production and decreased adiponectin levels in adipocyte cocultures. Estrogen at physiologic concentrations decreased TNF-α, IL-6, and preserved adiponectin levels following epi and/or H/R conditions. There was no effect of DHT on mitigating the proinflammatory response. Our results suggest a gender dimorphism in adipose tissue under stress conditions that may explain the conflicting data in the literature.
肥胖是一种慢性低度炎症状态，与脂肪组织分泌促炎细胞因子和脂肪因子有关。损伤和失血性休克后已发现性别二态性（部分归因于性激素）。我们假设性激素雌激素（E2）和睾酮（DHT）在应激条件下对脂肪组织中炎症介质的产生有不同影响。这在体外模型中进行了研究。
将从脂肪来源干细胞分化的成熟脂肪细胞与巨噬细胞（RAW 264.7）以2:1的比例共培养，并进行缺氧/复氧（H/R）和/或用生理浓度（10 μM）或应激浓度（10 μM）的肾上腺素（epi）孵育。添加一系列生理浓度的雌激素或DHT，孵育12小时后获得培养上清液，通过酶联免疫吸附测定法测量肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）和脂联素水平。
共培养物中基础TNF-α和IL-6的释放因epi和/或H/R条件而显著增加。雌激素将细胞因子释放降低至基础水平，而DHT没有影响。值得注意的是，改变epi的浓度对细胞因子释放没有影响。基础脂联素释放水平因epi和/或H/R条件而显著降低。雌激素暴露使脂联素水平恢复至基础水平，而DHT没有影响。在性激素对瘦素释放的影响方面观察到这种关系的相反情况。雌激素使瘦素释放恢复至基础水平，而DHT没有影响。
epi和H/R的应激水平增加了脂肪细胞共培养物中促炎细胞因子的产生并降低了脂联素水平。生理浓度的雌激素在epi和/或H/R条件后降低了TNF-α、IL-6并维持了脂联素水平。DHT对减轻促炎反应没有影响。我们的结果表明应激条件下脂肪组织存在性别二态性，这可能解释了文献中相互矛盾的数据。
