Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong Province, China.
Exp Clin Endocrinol Diabetes. 2023 Nov;131(11):595-604. doi: 10.1055/a-2178-9113. Epub 2023 Sep 20.
Pioglitazone is an insulin sensitizer used for the treatment of type 2 diabetes mellitus (T2DM) by activating peroxisome proliferator-activated receptor gamma. This study aimed to investigate the effects of pioglitazone on white adipose tissue (WAT) and brown adipose tissue (BAT) in diet-induced obese (DIO) mice.
C57BL/6 mice were treated with pioglitazone (30 mg/kg/day) for 4 weeks after a 16-week high-fat diet (HFD) challenge. Body weight gain, body fat mass, energy intake, and glucose homeostasis were measured during or after the treatment. Histopathology was observed by hematoxylin and eosin, oil red O, immunohistochemistry, and immunofluorescence staining. Expression of thermogenic and mitochondrial biogenesis-related genes was detected by quantitative real-time PCR and western blotting.
After 4-week pioglitazone treatment, the fasting blood glucose levels, glucose tolerance, and insulin sensitivity were significantly improved, but the body weight gain and fat mass were increased in DIO mice. Compared with the HFD group, pioglitazone did not significantly affect the weights of liver and WAT in both subcutaneous and epididymal regions. Unexpectedly, the weight of BAT was increased after pioglitazone treatment. Histological staining revealed that pioglitazone ameliorated hepatic steatosis, reduced the adipocyte size in WAT, but increased the adipocyte size in BAT.
Though pioglitazone can promote lipolysis, thermogenesis, and mitochondrial function in WAT, it leads to impaired thermogenesis, and mitochondrial dysfunction in BAT. In conclusion, pioglitazone could promote the browning of WAT but led to the whitening of BAT; the latter might be a new potential mechanism of pioglitazone-induced weight gain during T2DM treatment.
吡格列酮是一种胰岛素增敏剂，通过激活过氧化物酶体增殖物激活受体 γ 用于治疗 2 型糖尿病（T2DM）。本研究旨在探讨吡格列酮对饮食诱导肥胖（DIO）小鼠白色脂肪组织（WAT）和棕色脂肪组织（BAT）的影响。
C57BL/6 小鼠在高脂肪饮食（HFD）挑战 16 周后，用吡格列酮（30mg/kg/天）治疗 4 周。在治疗期间或之后测量体重增加、体脂肪量、能量摄入和葡萄糖稳态。通过苏木精和伊红、油红 O、免疫组织化学和免疫荧光染色观察组织病理学。通过定量实时 PCR 和 Western blot 检测产热和线粒体生物发生相关基因的表达。
吡格列酮治疗 4 周后，DIO 小鼠的空腹血糖水平、葡萄糖耐量和胰岛素敏感性显著改善，但体重增加和脂肪量增加。与 HFD 组相比，吡格列酮对皮下和附睾区域的 WAT 和肝重没有显著影响。出乎意料的是，吡格列酮治疗后 BAT 的重量增加。组织学染色显示，吡格列酮改善了肝脂肪变性，减少了 WAT 中脂肪细胞的大小，但增加了 BAT 中脂肪细胞的大小。
尽管吡格列酮可以促进 WAT 中的脂肪分解、产热和线粒体功能，但它导致 BAT 产热和线粒体功能受损。总之，吡格列酮可以促进 WAT 的褐变，但导致 BAT 的白化；后者可能是吡格列酮在 T2DM 治疗期间引起体重增加的新潜在机制。
