Department of Physiology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
Monash Biomedicine Discovery Institute; Metabolism, Diabetes and Obesity and Cancer Programs. Monash University, Clayton, Victoria, Australia.
Am J Physiol Endocrinol Metab. 2020 Sep 1;319(3):E519-E528. doi: 10.1152/ajpendo.00373.2019. Epub 2020 Jun 30.
Regional distribution of adipose tissue is an important factor in conferring cardiometabolic risk and obesity-related morbidity. We tested the hypothesis that human visceral adipose tissue (VAT) impairs glucose homeostasis, whereas subcutaneous glutealfemoral adipose tissue (GFAT) protects against the development of impaired glucose homeostasis in mice. VAT and GFAT were collected from patients undergoing bariatric surgery and grafted onto the epididymal adipose tissue of weight- and age-matched severe, combined immunodeficient mice. SHAM mice underwent surgery without transplant of tissue. Mice were fed a high-fat diet after xenograft. Energy homeostasis, glucose metabolism, and insulin sensitivity were assessed 6 wk later. Xenograft of human adipose tissues was successful, as determined by histology, immunohistochemical evaluation of collagen deposition and angiogenesis, and maintenance of lipolytic function. Adipose tissue transplant did not affect energy expenditure, food intake, whole body substrate partitioning, or plasma free fatty acid, triglyceride, and insulin levels. Fasting blood glucose was significantly reduced in GFAT and VAT compared with SHAM, whereas glucose tolerance was improved only in mice transplanted with VAT compared with SHAM mice. This improvement was not associated with differences in whole body insulin sensitivity or plasma insulin between groups. Together, these data suggest that VAT improves glycemic control and GFAT does not protect against the development of high-fat diet-induced glucose intolerance. Hence, the intrinsic properties of VAT and GFAT do not necessarily explain the postulated negative and positive effects of these adipose tissue depots on metabolic health.
脂肪组织的区域分布是影响心血管代谢风险和肥胖相关发病率的一个重要因素。我们验证了这样一个假设，即人类内脏脂肪组织（VAT）会损害葡萄糖稳态，而皮下臀股脂肪组织（GFAT）则可以防止肥胖相关的葡萄糖稳态受损。我们从接受减肥手术的患者身上采集 VAT 和 GFAT，并将其移植到体重和年龄匹配的严重联合免疫缺陷小鼠的附睾脂肪组织上。假手术组（SHAM）小鼠只接受手术但不移植组织。异种移植后，小鼠被喂食高脂肪饮食。6 周后评估能量稳态、葡萄糖代谢和胰岛素敏感性。通过组织学、胶原沉积和血管生成的免疫组织化学评估以及脂肪分解功能的维持，确定了人脂肪组织的异种移植是成功的。脂肪组织移植不会影响能量消耗、食物摄入、全身底物分布或血浆游离脂肪酸、甘油三酯和胰岛素水平。与 SHAM 相比，GFAT 和 VAT 组的空腹血糖显著降低，而只有 VAT 移植组的小鼠与 SHAM 组相比，葡萄糖耐量得到改善。这种改善与各组之间的全身胰岛素敏感性或血浆胰岛素水平没有差异有关。综上所述，这些数据表明 VAT 改善了血糖控制，而 GFAT 并不能防止高脂肪饮食引起的葡萄糖耐量受损。因此，VAT 和 GFAT 的内在特性并不一定能解释这些脂肪组织库对代谢健康的假定的负面和正面影响。
