Vratarić Miloš, Teofilović Ana, Milutinović Danijela Vojnović, Veličković Nataša, Vučićević Ljubica, Đmura Goran, Djordjevic Ana
Department of Biochemistry, Institute for Biological Research "Siniša Stanković"- National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia.
Department of Biochemistry, Institute for Biological Research "Siniša Stanković"- National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia.
J Nutr Biochem. 2025 Jul;141:109912. doi: 10.1016/j.jnutbio.2025.109912. Epub 2025 Apr 1.
Obesity is characterized by an enlargement of white adipose tissue caused by caloric excess. The depot-specific adaptation of white adipose tissue in individuals resistant to obesity despite a high-calorie diet is crucial for understanding the pathogenesis of obesity and related metabolic disorders. Our aim was to characterize the metabolic and morphological state of obesity resistance and to investigate depot-specific changes in signaling pathways in epididymal visceral (eVAT) and inguinal subcutaneous (iSAT) white adipose tissue of C57BL/6J male mice on a high-fat diet (60 kcal% fats). After 14 weeks, the mice were categorized as obese (at least 30% higher body mass compared to the control group) or obesity-resistant (weight gain below 30%). Biochemical and morphological parameters, as well as histology, and signaling pathways involved in lipid metabolism, inflammation, and insulin sensitivity were investigated in eVAT and iSAT. The results showed unaltered body, total VAT and iSAT mass in obesity-resistant mice despite increased caloric intake. Leptin levels and glucose homeostasis were improved in these animals compared to the obese mice. In both eVAT and iSAT of the obesity-resistant mice, adipocyte size and lipolytic capacity were retained at control levels, while compared to the obese mice, preserved capacity for adipogenesis, improved local insulin sensitivity and the absence of inflammation were observed only in the eVAT. In conclusion, metabolic adaptation of eVAT rather than iSAT may have a substantial impact on the maintenance of the obesity-resistant phenotype with fewer metabolic complications, which could contribute to the improvement of existing obesity therapies.
肥胖的特征是热量摄入过多导致白色脂肪组织增大。对于尽管高热量饮食但仍对肥胖具有抗性的个体而言，白色脂肪组织的特定储存部位适应性对于理解肥胖症及相关代谢紊乱的发病机制至关重要。我们的目的是表征抗肥胖的代谢和形态状态，并研究高脂饮食（60千卡%脂肪）的C57BL/6J雄性小鼠附睾内脏（eVAT）和腹股沟皮下（iSAT）白色脂肪组织中信号通路的特定储存部位变化。14周后，将小鼠分为肥胖组（体重比对照组至少高30%）或抗肥胖组（体重增加低于30%）。对eVAT和iSAT中的生化和形态学参数、组织学以及参与脂质代谢、炎症和胰岛素敏感性的信号通路进行了研究。结果显示，尽管热量摄入增加，但抗肥胖小鼠的体重、总内脏脂肪组织和皮下脂肪组织质量未发生改变。与肥胖小鼠相比，这些动物的瘦素水平和葡萄糖稳态得到改善。在抗肥胖小鼠的eVAT和iSAT中，脂肪细胞大小和脂解能力均维持在对照水平，而与肥胖小鼠相比，仅在eVAT中观察到脂肪生成能力得以保留、局部胰岛素敏感性提高且无炎症反应。总之，eVAT而非iSAT的代谢适应性可能对维持抗肥胖表型并减少代谢并发症具有重大影响，这可能有助于改进现有的肥胖治疗方法。
