Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
Mol Med Rep. 2017 Nov;16(5):6771-6779. doi: 10.3892/mmr.2017.7461. Epub 2017 Sep 11.
It has previously been demonstrated that apolipoprotein A5 (apoA5) can be internalized by human adipocytes and significantly decreases intracellular triglyceride content. In the present study, endocytosis of apoA5 by adipocytes under different conditions, and the underlying mechanism by which apoA5 regulates cellular triglyceride storage, was investigated. The results revealed that the apoA5 protein was detected in human subcutaneous abdominal adipose tissues. In addition, the uptake of apoA5 was attenuated in human obese adipose tissues and in cultured adipocytes with hypertrophy or insulin resistance. Low‑density lipoprotein receptor protein 1 (LRP1) knockdown in adipocytes resulted in a decrease in internalized apoA5 content, suggesting that LRP1 serves a role in apoA5 uptake. Treatment of adipocytes with apoA5 decreased the expression of the lipid droplet‑associated proteins such as cidec and perilipin. ApoA5‑treated adipocytes demonstrated an increase in lipolysis activity and expression of uncoupling protein 1, which is the molecular effector of thermogenesis in brown adipocytes. These results suggested that decreased triglyceride accumulation in adipocytes induced by apoA5 may be associated with enhanced lipolysis and energy expenditure, which may result from reduced expression of cidec and perilipin. In conclusion, the present study demonstrated a novel role of apoA5 in regulating the intracellular triglyceride metabolism of adipocytes. The results of the present study suggested that apoA5 may serve as a potential therapeutic target for the treatment of obesity and its related disorders.
先前已有研究表明，载脂蛋白 A5（apoA5）可被人类脂肪细胞内化，并显著降低细胞内甘油三酯含量。本研究旨在探究脂肪细胞在不同条件下内化 apoA5 的情况，以及 apoA5 调节细胞内甘油三酯储存的潜在机制。结果表明，apoA5 蛋白在人体皮下腹部脂肪组织中被检测到。此外，在肥胖脂肪组织和发生肥大或胰岛素抵抗的培养脂肪细胞中，apoA5 的摄取被减弱。脂肪细胞中 LDL 受体蛋白 1（LRP1）的敲低导致内化 apoA5 含量减少，表明 LRP1 参与 apoA5 的摄取。apoA5 处理脂肪细胞后，脂滴相关蛋白如 cidec 和 perilipin 的表达减少。apoA5 处理的脂肪细胞表现出脂肪分解活性和解偶联蛋白 1 的表达增加，解偶联蛋白 1 是棕色脂肪细胞产热的分子效应物。这些结果表明，apoA5 诱导脂肪细胞内甘油三酯积累减少可能与增强的脂肪分解和能量消耗有关，这可能是由于 cidec 和 perilipin 的表达减少所致。综上所述，本研究证明了 apoA5 在调节脂肪细胞内甘油三酯代谢方面的新作用。本研究结果表明，apoA5 可能成为治疗肥胖及其相关疾病的潜在治疗靶点。
