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Role of acetoacetyl-CoA synthetase in glucose uptake by HepG2 cells

Role of acetoacetyl-CoA synthetase in glucose uptake by HepG2 cells

来源:bioRxiv_logobioRxiv
英文摘要

Accelerated glucose metabolism is a common feature of cancer cells and represents a potential therapeutic target. Recent studies have revealed that lipid metabolism is related to glucose me-tabolism, especially glucose uptake. Acetoacetyl-CoA synthetase (AACS) converts acetoacetate, a ketone body, to acetoacetyl-CoA, which is incorporated into cholesterol and fatty acids. The AACS gene is highly expressed in HepG2 cells but not in the human normal liver. These results suggest a correlation between AACS and glucose metabolism. Therefore, we examined the relationship between AACS and glucose uptake in hepatocellular carcinoma (HepG2) cells. The expression of AACS was significantly upregulated when HepG2 cells were exposed to high concentrations of glucose. Lentiviruses, which code for shRNA against AACS (shAACS), were used to determine whether AACS knockdown affects the glucose uptake in HepG2 cells. AACS knockdown significantly reduced glucose uptake and increased the concentration of ketone bodies in the media, and treatment with beta-hydroxybutyrate, a ketone body, attenuated glucose uptake. Moreover, the knockdown of AACS, i.e., the increased concentration of the intracellular ketone body, slightly attenuated cell proliferation and significantly increased the sensitivity to the anticancer agent sorafenib. These results suggest that AACS plays an important role in glucose uptake and cell proliferation and that ketone bodies may compete with glucose as an important energy source for cancer cells.

Takahashi Noriko、Hasegawa Shinya、Imai Masahiko

10.1101/2023.02.04.527056

基础医学生物化学肿瘤学

Takahashi Noriko,Hasegawa Shinya,Imai Masahiko.Role of acetoacetyl-CoA synthetase in glucose uptake by HepG2 cells[EB/OL].(2025-03-28)[2025-04-27].https://www.biorxiv.org/content/10.1101/2023.02.04.527056.点此复制

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