Institute of Physical Science and Information Technology, Institute of Health Sciences Anhui University, Hefei, Anhui 230601, PR China.
School of Life Science, Anhui University, Hefei, Anhui 230601, PR China.
Biochim Biophys Acta Mol Cell Biol Lipids. 2023 Oct;1868(10):159369. doi: 10.1016/j.bbalip.2023.159369. Epub 2023 Aug 14.
Brown adipose tissue (BAT) is thermogenic, expressing high levels of uncoupling protein-1 to convert nutrient energy to heat energy, bypassing ATP synthesis. BAT is a promising therapeutic target for treatment of obesity and type 2 diabetes since it converts fatty acids into heat but mechanisms controlling brown adipogenesis remain unclear. Knockdown of acetyl-Coenzyme A acetyltransferase 1 (ACAT1) in C3H10T1/2 cells suppressed brown adipocyte maturation during the current study and ACAT1 overexpression promoted brown adipocyte maturation. The downstream target of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1-α (PGC1α), was involved in the action of ACAT1 on brown adipocyte maturation. ACAT1 overexpression enhanced AMPK phosphorylation and promoted PGC1α expression. It is suggested that ACAT1 promotes brown adipocyte maturation by activating the AMPK-PGC1α signaling pathway.
棕色脂肪组织(BAT)是产热组织,表达高水平的解偶联蛋白 1 将营养能转化为热能,绕过 ATP 合成。BAT 是治疗肥胖症和 2 型糖尿病的有前途的治疗靶点,因为它将脂肪酸转化为热量,但控制棕色脂肪生成的机制仍不清楚。在本研究中,ACAT1 的乙酰辅酶 A 乙酰转移酶 1(ACAT1)的敲低抑制了 C3H10T1/2 细胞中棕色脂肪细胞的成熟,而 ACAT1 的过表达促进了棕色脂肪细胞的成熟。AMP 激活的蛋白激酶(AMPK)的下游靶标,过氧化物酶体增殖物激活受体γ共激活因子 1-α(PGC1α),参与了 ACAT1 对棕色脂肪细胞成熟的作用。ACAT1 的过表达增强了 AMPK 的磷酸化并促进了 PGC1α 的表达。提示 ACAT1 通过激活 AMPK-PGC1α 信号通路促进棕色脂肪细胞成熟。