Metabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Int J Mol Sci. 2023 Feb 8;24(4):3412. doi: 10.3390/ijms24043412.
Glycerol is a key metabolite for lipid accumulation in insulin-sensitive tissues. We examined the role of aquaporin-7 (AQP7), the main glycerol channel in adipocytes, in the improvement of brown adipose tissue (BAT) whitening, a process whereby brown adipocytes differentiate into white-like unilocular cells, after cold exposure or bariatric surgery in male Wistar rats with diet-induced obesity (DIO) ( = 229). DIO promoted BAT whitening, evidenced by increased BAT hypertrophy, steatosis and upregulation of the lipogenic factors , and . AQP7 was detected in BAT capillary endothelial cells and brown adipocytes, and its expression was upregulated by DIO. Interestingly, AQP7 gene and protein expressions were downregulated after cold exposure (4 °C) for 1 week or one month after sleeve gastrectomy in parallel to the improvement of BAT whitening. Moreover, mRNA expression was positively associated with transcripts of the lipogenic factors , and and regulated by lipogenic (ghrelin) and lipolytic (isoproterenol and leptin) signals. Together, the upregulation of AQP7 in DIO might contribute to glycerol influx used for triacylglycerol synthesis in brown adipocytes, and hence, BAT whitening. This process is reversible by cold exposure and bariatric surgery, thereby suggesting the potential of targeting BAT AQP7 as an anti-obesity therapy.
甘油是胰岛素敏感组织中脂质积累的关键代谢物。我们研究了水通道蛋白-7(AQP7)在改善棕色脂肪组织(BAT)白化中的作用,AQP7 是脂肪细胞中主要的甘油通道。在饮食诱导肥胖(DIO)的雄性 Wistar 大鼠中,冷暴露或减肥手术(=229)后,BAT 会发生白化,即棕色脂肪细胞分化为类似白色的单房细胞。DIO 促进了 BAT 的白化,表现为 BAT 肥大、脂肪变性和脂生成因子 和 的上调。AQP7 存在于 BAT 毛细血管内皮细胞和棕色脂肪细胞中,并且其表达在 DIO 中上调。有趣的是,冷暴露(4°C)1 周或袖状胃切除术后 1 个月后,AQP7 基因和蛋白表达均下调,与 BAT 白化的改善平行。此外,mRNA 表达与脂生成因子 和 的转录物呈正相关,并且受到脂生成(ghrelin)和脂解(异丙肾上腺素和瘦素)信号的调节。总之,DIO 中 AQP7 的上调可能有助于甘油流入棕色脂肪细胞以合成三酰甘油,从而导致 BAT 白化。该过程可通过冷暴露和减肥手术逆转,因此提示靶向 BAT AQP7 作为肥胖治疗的潜在可能性。