Touceda Vanessa, Fontana Estevez Florencia, Cacciagiú Leonardo, Finocchietto Paola, Bustos Romina, Vidal Agustina, Berg Gabriela, Morales Celina, González Germán, Miksztowicz Veronica
Pontificia Universidad Católica Argentina. Facultad de Medicina, Instituto de Investigaciones Biomédicas (UCA-CONICET), Laboratorio de Patología Cardiovascular Experimental e Hipertensión Arterial, Buenos Aires, Argentina.
Universidad de Buenos Aires, Facultad de Odontología, Cátedra de Bioquímica General y Bucal, Buenos Aires, Argentina.
Curr Res Pharmacol Drug Discov. 2024 May 23;6:100185. doi: 10.1016/j.crphar.2024.100185. eCollection 2024.
Central obesity is characterized by visceral adipose tissue (VAT) expansion, considered one of the main risk factors for metabolic complications. In recent years, new drugs have been studied for obesity treatment. Liraglutide (LGT), a GLP-1 agonist, decreases body weight, however, several mechanisms of action on VAT are still unknown.
to study the effect of LGT on factors associated with VAT remodeling and mitochondrial dynamics in mice fed a high-fat diet (HFD).
C57BL/6 mice were divided into Control (C) and HFD. After 15 weeks of feeding, each group was subdivided according to LGT administration for 5 weeks: C, C + LGT, HFD, and HFD + LGT. In epididymal AT (EAT) we evaluated histological and mitochondrial characteristics, vascularity, gelatinase activity (MMPs), and galectin-3 expression.
HFD presented larger adipocytes (p < 0.05), and lower vascular density and MMP-9 activity (p < 0.01) than C, while a major number of smaller adipocytes (p < 0.05) and an increase in vascularity (p < 0.001) and MMP-9 activity (p < 0.01) was observed in HFD + LGT. Collagen content was higher (p < 0.05) in EAT from HFD and decreased in HFD + LGT. In C, C + LGT, and HFD + LGT, mitochondria were predominantly tubular-shaped while in HFD mitochondria were mostly spherical (p < 0.001).
LGT positively influences VAT behavior by modulating gelatinase activity, enhancing vascularization, and improving adipocyte histological characteristics. Additionally, LGT improves mitochondrial dynamics, a process that would favor VAT functionality.
中心性肥胖的特征是内脏脂肪组织（VAT）扩张，被认为是代谢并发症的主要危险因素之一。近年来，人们对用于肥胖治疗的新药进行了研究。利拉鲁肽（LGT）是一种胰高血糖素样肽-1（GLP-1）激动剂，可减轻体重，然而，其对内脏脂肪组织的几种作用机制仍不清楚。
研究LGT对高脂饮食（HFD）喂养小鼠中与内脏脂肪组织重塑和线粒体动力学相关因素的影响。
将C57BL/6小鼠分为对照组（C）和高脂饮食组。喂养15周后，根据是否给予LGT 5周将每组再细分：C组、C + LGT组、HFD组和HFD + LGT组。在附睾脂肪组织（EAT）中，我们评估了组织学和线粒体特征、血管化、明胶酶活性（基质金属蛋白酶）和半乳糖凝集素-3表达。
与C组相比，HFD组呈现更大的脂肪细胞（p < 0.05），以及更低的血管密度和基质金属蛋白酶-9活性（p < 0.01），而在HFD + LGT组中观察到大量较小的脂肪细胞（p < 0.05）以及血管化增加（p < 0.001）和基质金属蛋白酶-9活性增加（p < 0.01）。HFD组EAT中的胶原蛋白含量更高（p < 0.05），而在HFD + LGT组中降低。在C组、C + LGT组和HFD + LGT组中，线粒体主要呈管状，而在HFD组中线粒体大多呈球形（p < 0.001）。
LGT通过调节明胶酶活性、增强血管化和改善脂肪细胞组织学特征，对内脏脂肪组织行为产生积极影响。此外，LGT改善线粒体动力学，这一过程有利于内脏脂肪组织的功能。
