Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan; College of Gastronomy Management, Ritsumeikan University, Shiga, Japan.
Graduate School of Human Development and Environment, Kobe University, Kobe, Japan.
Biochem Biophys Res Commun. 2020 Jul 30;528(3):612-619. doi: 10.1016/j.bbrc.2020.05.136. Epub 2020 Jun 3.
Substantial evidence has linked dehydroepiandrosterone (DHEA) levels to the anti-obesity and anti-diabetic effects of exercise. While 5'-adenosine monophosphate-activated protein kinase (AMPK) is a negative regulator of adipocyte differentiation and lipid accumulation, activation of mammalian target of rapamycin complex 1 (mTORC1), which is inhibited by AMPK, is required for adipocyte differentiation and positively regulates lipid accumulation. DHEA treatment activates the AMPK pathway in C2C12 myotubes. Hence, DHEA addition to preadipocytes and adipocytes might activate AMPK and inhibit mTORC1, resulting in the inhibition of adipogenesis and lipid accumulation. Therefore, we investigated the effect of DHEA on the AMPK pathway, mTORC1 activity, adipocyte differentiation, and lipid accumulation in 3T3-L1 cells. DHEA suppressed lipid accumulation and adipogenic marker expression during differentiation. It also activated AMPK signaling in preadipocytes and adipocytes and suppressed mTORC1 activity during differentiation. These results suggest that the activation of the AMPK pathway and inhibition of mTORC1 activity may mediate the anti-obesity effect of DHEA, providing novel molecular-level insights into its physiological functions.
大量证据表明脱氢表雄酮（DHEA）水平与运动的抗肥胖和抗糖尿病作用有关。虽然 5'-腺苷单磷酸激活蛋白激酶（AMPK）是脂肪细胞分化和脂质积累的负调节剂，但需要激活哺乳动物雷帕霉素靶蛋白复合物 1（mTORC1），AMPK 抑制 mTORC1 的活性，这对于脂肪细胞分化是必需的，并正向调节脂质积累。DHEA 处理可激活 C2C12 肌管中的 AMPK 途径。因此，DHEA 可能会添加到前体脂肪细胞和脂肪细胞中，从而激活 AMPK 并抑制 mTORC1，导致脂肪生成和脂质积累受到抑制。因此，我们研究了 DHEA 对 3T3-L1 细胞中 AMPK 途径、mTORC1 活性、脂肪细胞分化和脂质积累的影响。DHEA 在分化过程中抑制脂质积累和脂肪生成标志物的表达。它还在前体脂肪细胞和脂肪细胞中激活 AMPK 信号，并在分化过程中抑制 mTORC1 活性。这些结果表明，AMPK 途径的激活和 mTORC1 活性的抑制可能介导 DHEA 的抗肥胖作用，为其生理功能提供了新的分子水平的见解。
