Karolinska Institutet, Department of Clinical Science, Danderyd Hospital & Department of Surgery, Ersta Hospital, 116 91 Stockholm, Sweden.
Clin Nutr. 2021 May;40(5):2602-2608. doi: 10.1016/j.clnu.2021.03.044. Epub 2021 Apr 20.
BACKGROUND & AIMS: Owing to the "obesity-pandemic", an increasing number of individuals are in need of treatment for obesity and obesity-related disorders. For patients with severe disease, results with conventional treatment modalities such as diet regimens, physical activity, and pharmacologic agents most often lack satisfactory efficacy and/or sustainability. In contrast, bariatric surgery has been demonstrated to be associated with marked, long-term weight loss as well as resolution or improvement of co-morbid disease, in particular metabolic aberrations such as insulin resistance and type 2 diabetes. The underlying mechanisms for the effects of surgery-induced weight loss on such morbidity are incompletely understood.
This article gives an updated overview of some aspects on the mechanisms involved in the improvement in metabolism in obese individuals submitted to surgery-induced weight loss. Patients undergoing Roux en-Y Gastric Bypass (RYGB) were studied before and at various times after the operation. Weight, body composition with determination of distribution of adipose tissue (DEXA), and insulin sensitivity (hyperinsulinemic clamp) was determined. In vitro; lipolytic activity and adipose morphology (fat cell size) was assessed.
Low calorie intake, rerouting of nutrients as well as loss of fat mass are all associated with improved insulin sensitivity after RYGB. In obese individuals, an increase in lipolytic activity in visceral adipose tissue might contribute to the association with cardiometabolic disease. However, selective reduction (omentectomy) seems not to improve insulin sensitivity or cardiometabolic risk. Adipose hyperplasia (many small cells) might be protective against metabolic abnormalities compared to hypertrophy (large cells). Preoperative fat cell size is related to improvement in insulin sensitivity after RYGB. Two years after weight loss, a change in adipose morphology to a more metabolically benign phenotype (remodeling) is seen, with a reduction of fat cell size which is correlated to the improvement in insulin sensitivity. Patients with weight regain 5 years after RYGB, still display a more benign metabolic profile compared to weight-matched controls.
Several factors contribute to the improvements in insulin sensitivity and cardiometabolic disease after surgery-induced weight loss, including low calorie intake rerouting of nutrients and loss of adipose tissue mass. Increased lipolytic activity in visceral adipose tissue as well as adipose hypertrophy relates to increased metabolic risk. RYGB-induced weight loss is associated with redistribution of adipose tissue as well as remodeling of fat cells to a more benign profile. Reduction of fat cell size might be a possible target to improve insulin sensitivity in patients with obesity in the future.
由于“肥胖流行”，越来越多的人需要治疗肥胖症和肥胖相关疾病。对于患有严重疾病的患者，常规治疗方法（如饮食、运动和药物治疗）的疗效往往不理想，且难以维持。相比之下，减重手术已被证明可显著长期减轻体重，并改善合并症，特别是代谢异常，如胰岛素抵抗和 2 型糖尿病。手术减肥对这些发病率的影响的潜在机制尚不完全清楚。
本文综述了手术减肥改善肥胖患者代谢的一些机制。对接受 Roux-en-Y 胃旁路术（RYGB）的患者进行术前和术后不同时间点的研究。测定体重、身体成分（使用 DEXA 测定脂肪组织分布）和胰岛素敏感性（高胰岛素钳夹试验）。体外评估脂肪分解活性和脂肪形态（脂肪细胞大小）。
RYGB 术后热量摄入减少、营养重排和脂肪量丢失均与胰岛素敏感性改善相关。在肥胖个体中，内脏脂肪组织脂肪分解活性增加可能与心血管代谢疾病相关。然而，选择性脂肪切除术（omentectomy）似乎并不能改善胰岛素敏感性或心血管代谢风险。与肥大（大细胞）相比，脂肪增生（许多小细胞）可能对代谢异常具有保护作用。术前脂肪细胞大小与 RYGB 后胰岛素敏感性的改善相关。减肥 2 年后，观察到脂肪形态向更有利于代谢的表型（重塑）转变，脂肪细胞大小减小，与胰岛素敏感性改善相关。RYGB 后 5 年体重反弹的患者，与体重匹配的对照组相比，仍表现出更良性的代谢特征。
RYGB 术后胰岛素敏感性和心血管代谢疾病改善的原因包括热量摄入减少、营养重排和脂肪组织质量丢失。内脏脂肪组织脂肪分解活性增加以及脂肪肥大与代谢风险增加相关。RYGB 诱导的体重减轻与脂肪组织再分布以及脂肪细胞重塑为更良性表型相关。减少脂肪细胞大小可能是未来肥胖患者改善胰岛素敏感性的一个潜在目标。
