Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
Physiol Rep. 2023 Sep;11(18):e15815. doi: 10.14814/phy2.15815.
While a definitive mechanism-of-action remains to be identified, recent findings indicate that ghrelin, particularly the unacylated form (UnAG), stimulates skeletal muscle fatty acid oxidation. The biological importance of UnAG-mediated increases in fat oxidation remains unclear, as UnAG peaks in the circulation before mealtimes, and decreases rapidly during the postprandial situation before increases in postabsorptive circulating lipids. Therefore, we aimed to determine if the UnAG-mediated stimulation of fat oxidation would persist long enough to affect the oxidation of meal-derived fatty acids, and if UnAG stimulated the translocation of fatty acid transporters to the sarcolemma as a mechanism-of-action. In isolated soleus muscle strips from male rats, short-term pre-treatment with UnAG elicited a persisting stimulus on fatty acid oxidation 2 h after the removal of UnAG. UnAG also caused an immediate phosphorylation of AMPK, but not an increase in plasma membrane FAT/CD36 or FABPpm. There was also no increase in AMPK signaling or increased FAT/CD36 or FABPpm content at the plasma membrane at 2 h which might explain the sustained increase in fatty acid oxidation. These findings confirm UnAG as a stimulator of fatty acid oxidation and provide evidence that UnAG may influence the handling of postprandial lipids. The underlying mechanisms are not known.
虽然作用机制仍未确定，但最近的研究结果表明，ghrelin，特别是未酰化形式（UnAG），可刺激骨骼肌脂肪酸氧化。UnAG 介导的脂肪氧化增加的生物学意义尚不清楚，因为 UnAG 在餐前循环中达到峰值，并且在餐后迅速下降，然后在吸收后循环脂质增加之前增加。因此，我们旨在确定 UnAG 介导的脂肪氧化刺激是否足够持久，以影响膳食来源的脂肪酸的氧化，以及 UnAG 是否通过将脂肪酸转运蛋白易位到肌膜作为作用机制来刺激脂肪酸氧化。在雄性大鼠的分离的比目鱼肌肌条中，UnAG 的短期预处理在去除 UnAG 后 2 小时引起脂肪酸氧化的持续刺激。UnAG 还立即引起 AMPK 的磷酸化，但不会增加质膜 FAT/CD36 或 FABPpm。在 2 小时时，质膜上也没有 AMPK 信号的增加或 FAT/CD36 或 FABPpm 含量的增加，这可能解释了脂肪酸氧化的持续增加。这些发现证实了 UnAG 是脂肪酸氧化的刺激剂，并提供了证据表明 UnAG 可能影响餐后脂质的处理。其潜在机制尚不清楚。
