Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.
Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China.
Biochem Biophys Res Commun. 2023 Jul 23;666:146-153. doi: 10.1016/j.bbrc.2023.05.015. Epub 2023 May 4.
People living in plains tend to decrease in body weight or body fat percentage after entering the plateau. Previous studies have found that plateau animals can burn fat and release calories through white adipose tissues (WATs) browning. However, these studies have focused on the effect of cold stimulation that induced WATs browning while there's hardly study on the effect of hypoxia. In this study, we investigate that whether and how hypoxia contributes to WATs browning in rats from acute to chronic hypoxia. We constructed hypobaric hypoxic rat models by exposing 9-week-old male SD rats to a hypobaric hypoxic chamber for 1, 3, 14 and 28 days (Group H) under simulated environment at altitude of 5000 m. We also established normoxic control groups for each time period (Group C), as well as paired 1-day and 14-day normoxic food-restriction rats that were fed the same amount of food as the hypoxic group ate (Group R). We then observed the growth status of rats and recorded dynamic changes in histologic, cellular and molecular levels of perirenal WATs (PWAT), epididymal WATs (EWAT) and subcutaneous WATs (SWAT) in each group. Results showed that (1) Hypoxic rats had lower food intake, significantly lower body weight than control rats, and showed lower WATs index. (2) In group H14, ASC1 mRNA expressions of PWAT and EWAT in rats were lower than that in group C14, and PAT2 mRNA expression of EWAT was higher than that in both group C14 and R14. In group R14, however, ASC1 mRNA expressions of PWAT and EWAT in rats were higher than both group C14 and H14, and that of SWAT was also significantly higher than group C14. (3) In group H3, both the mRNA and protein levels of uncoupling protein 1 (UCP1) of PWAT in rats were significantly increased than group C3. And in group H14, those of EWAT in rats were significantly increased than group C14. (4) In plasma of rats, norepinephrine (NE) level was significantly increased in group H3 than group C3, and free fatty acids (FFAs) level was significantly increased in group H14 than both group C14 and R14. In group R1, FASN mRNA expressions of PWAT and EWAT in rats were down-regulated than group C1. In group H3, FASN mRNA expressions of PWAT and EWAT in rats were down-regulated while ATGL mRNA expression of EWAT was up-regulated than group C3. Conversely, in group R14, FASN mRNA expressions of PWAT and EWAT in rats were significantly up-regulated than group C14 and H14. These results suggested that hypoxia promoted different WATs browning in rats under simulated environment at altitude of 5000 m and changed the lipid metabolism in WATs. Furthermore, rats in the chronic hypoxic group showed a completely different lipid metabolism of WATs from that in paired food-restriction group.
居住在平原地区的人进入高原后，体重或体脂百分比往往会下降。先前的研究发现，高原动物可以通过白色脂肪组织（WAT）褐变来燃烧脂肪并释放热量。然而，这些研究主要集中在冷刺激诱导 WAT 褐变的效果上，而对于缺氧的影响几乎没有研究。在这项研究中，我们研究了急性到慢性缺氧过程中，缺氧是否以及如何促进大鼠 WAT 褐变。我们通过将 9 周龄雄性 SD 大鼠置于模拟海拔 5000 米的低压缺氧室中 1、3、14 和 28 天（H 组），构建了低压缺氧大鼠模型。我们还为每个时间段建立了正常氧对照（C 组），以及配对的 1 天和 14 天正常氧限食大鼠，这些大鼠摄入与缺氧组相同量的食物（R 组）。然后，我们观察了大鼠的生长状况，并记录了各组肾周 WAT（PWAT）、附睾 WAT（EWAT）和皮下 WAT（SWAT）在组织学、细胞和分子水平上的动态变化。结果表明：（1）缺氧大鼠的食物摄入量较低，体重明显低于对照组，WATs 指数也较低。（2）在 H14 组中，大鼠 PWAT 和 EWAT 的 ASC1mRNA 表达低于 C14 组，而 EWAT 的 PAT2mRNA 表达高于 C14 组和 R14 组。然而，在 R14 组中，大鼠 PWAT 和 EWAT 的 ASC1mRNA 表达均高于 C14 组和 H14 组，SWAT 的表达也明显高于 C14 组。（3）在 H3 组中，大鼠 PWAT 的解偶联蛋白 1（UCP1）的 mRNA 和蛋白水平均明显高于 C3 组。在 H14 组中，大鼠 EWAT 的 UCP1 的 mRNA 和蛋白水平均明显高于 C14 组。（4）在大鼠的血浆中，H3 组的去甲肾上腺素（NE）水平明显高于 C3 组，H14 组的游离脂肪酸（FFAs）水平明显高于 C14 组和 R14 组。在 R1 组中，大鼠 PWAT 和 EWAT 的 FASNmRNA 表达低于 C1 组。在 H3 组中，大鼠 PWAT 和 EWAT 的 FASNmRNA 表达低于 C3 组，而 EWAT 的 ATGLmRNA 表达高于 C3 组。相反，在 R14 组中，大鼠 PWAT 和 EWAT 的 FASNmRNA 表达明显高于 C14 组和 H14 组。这些结果表明，在模拟海拔 5000 米的环境下，缺氧促进了大鼠不同部位 WAT 的褐变，并改变了 WAT 的脂质代谢。此外，慢性缺氧组大鼠的 WAT 脂质代谢与配对限食组完全不同。
