Pastel Emilie, McCulloch Laura J, Ward Rebecca, Joshi Shivam, Gooding Kim M, Shore Angela C, Kos Katarina
Diabetes and Obesity Research Group, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW, U.K.
Diabetes and Vascular Medicine, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW, U.K.
Clin Sci (Lond). 2017 Mar 1;131(5):343-353. doi: 10.1042/CS20160803. Epub 2017 Jan 3.
Glucagon-like peptide-1 (GLP-1) analogues aid weight loss that improves obesity-associated adipose tissue (AT) dysfunction. GLP-1 treatment may however also directly influence AT that expresses the GLP-1 receptor (GLP-1R). The present study aimed to assess the impact of GLP-1 analogue treatment on subcutaneous AT (SCAT) inflammatory and fibrotic responses, compared with weight loss by calorie reduction (control). Among the 39 participants with Type 2 diabetes recruited, 30 age-matched participants were randomized to 4 months treatment with Liraglutide (=22) or calorie restriction based on dietetic counselling (=8). Assessments included clinical characteristics and repeated subcutaneous abdominal AT biopsies. Liraglutide resulted in weight loss in most participants (-3.12±1.72 kg, =0.007) and significant reduction in visceral AT (VAT). It was more effective in lowering fasting glucose, in comparison with weight loss by dieting. However, tumour necrosis factor-α () AT-expression (=0.0005), macrophage chemoattractant protein-1 () expression (=0.027) and its serum levels (=0.048) increased with Liraglutide, suggestive of an inflammatory response unlike in the diet arm in which a trend of lower cluster of differentiation 14 () expression (=0.09) was found. Liraglutide treatment also increased expression of factors involved in extracellular matrix (ECM) deposition, transforming growth factor-β () and collagen type 1 alpha 1 chain () (: before 0.73±0.09 arbitrary units (AU), after 1.00±0.13 AU, =0.006; : 0.84±0.09 AU compared with 1.49±0.26 AU, =0.026). Liraglutide thus appears to induce an inflammatory response in AT and influences ECM remodelling. Despite its superior effect on glycaemia, Liraglutide does not improve obesity-associated AT dysfunction in subcutaneous tissue. It is yet unclear whether this limits AT storage capacity for lipids. This may be of importance in patients being re-exposed to positive energy balance such as post GLP-1 discontinuation.
胰高血糖素样肽-1（GLP-1）类似物有助于减轻体重，改善与肥胖相关的脂肪组织（AT）功能障碍。然而，GLP-1治疗也可能直接影响表达GLP-1受体（GLP-1R）的脂肪组织。本研究旨在评估GLP-1类似物治疗对皮下脂肪组织（SCAT）炎症和纤维化反应的影响，并与通过减少热量摄入实现体重减轻（对照组）进行比较。在招募的39名2型糖尿病参与者中，30名年龄匹配的参与者被随机分为两组，分别接受4个月的利拉鲁肽治疗（=22）或基于饮食咨询的热量限制治疗（=8）。评估内容包括临床特征和重复进行的腹部皮下脂肪组织活检。利拉鲁肽使大多数参与者体重减轻（-3.12±1.72千克，=0.007），内脏脂肪组织（VAT）显著减少。与节食减重相比，利拉鲁肽在降低空腹血糖方面更有效。然而，利拉鲁肽使肿瘤坏死因子-α（）在脂肪组织中的表达（=0.0005）、巨噬细胞趋化蛋白-1（）的表达（=0.027）及其血清水平（=0.048）升高，提示存在炎症反应，这与节食组不同，节食组发现分化簇14（）表达有降低趋势（=0.09）。利拉鲁肽治疗还增加了参与细胞外基质（ECM）沉积的因子、转化生长因子-β（）和1型胶原α1链（）的表达（：治疗前为0.73±0.09任意单位（AU），治疗后为1.00±0.13 AU，=0.006；：0.84±0.09 AU与1.49±0.26 AU相比，=0.026）。因此，利拉鲁肽似乎会在脂肪组织中诱导炎症反应并影响ECM重塑。尽管利拉鲁肽对血糖有更好的效果，但它并不能改善皮下组织中与肥胖相关的脂肪组织功能障碍。目前尚不清楚这是否会限制脂肪组织对脂质的储存能力。这对于再次暴露于正能量平衡的患者（如停用GLP-1后）可能具有重要意义。
