Department Chemistry and Molecular Biology, Univ. Gothenburg, Box 462, 405 30, Gothenburg, Sweden.
Department Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, Univ. of Gothenburg, 405 30, Gothenburg, Sweden.
Lipids Health Dis. 2021 Nov 28;20(1):173. doi: 10.1186/s12944-021-01600-y.
AdipoR1 and AdipoR2 (AdipoRs) are plasma membrane proteins often considered to act as adiponectin receptors with a ceramidase activity. Additionally, the AdipoRs and their yeast and C. elegans orthologs are emerging as membrane homeostasis regulators that counter membrane rigidification by promoting fatty acid desaturation and incorporation of unsaturated fatty acids into phospholipids, thus restoring fluidity.
Using cultured cells, the effects of AdipoR silencing or over-expression on the levels and composition of several sphingolipid classes were examined.
AdipoR2 silencing in the presence of exogenous palmitic acid potently causes increased levels of dihydroceramides, a ceramide precursor in the de novo ceramide synthesis pathway. Conversely, AdipoR2 over-expression caused a depletion of dihydroceramides.
The results are consistent with AdipoR2 silencing leading to increased intracellular supply of palmitic acid that in turn leads to increased dihydroceramide synthesis via the rate-limiting serine palmitoyl transferase step. In agreement with this model, inhibiting the desaturase SCD or SREBF1/2 (positive regulators of SCD) also causes a strong increase in dihydroceramide levels.
脂联素受体 1 和 2（AdipoRs）是常被认为具有神经酰胺酶活性的作为脂联素受体的质膜蛋白。此外，AdipoRs 及其酵母和秀丽隐杆线虫的同源物正作为膜稳态调节剂出现，通过促进脂肪酸去饱和和将不饱和脂肪酸掺入磷脂中来对抗膜刚性化，从而恢复流动性。
使用培养的细胞，研究了 AdipoR 沉默或过表达对几种神经鞘脂类水平和组成的影响。
在存在外源性棕榈酸的情况下，AdipoR2 沉默强烈导致二氢神经酰胺水平升高，二氢神经酰胺是从头合成神经酰胺途径中的神经酰胺前体。相反，AdipoR2 过表达导致二氢神经酰胺耗竭。
这些结果与 AdipoR2 沉默导致细胞内棕榈酸供应增加一致，而棕榈酸供应增加又通过限速丝氨酸棕榈酰转移酶步骤导致二氢神经酰胺合成增加。与该模型一致，抑制去饱和酶 SCD 或 SREBF1/2（SCD 的正调节剂）也会导致二氢神经酰胺水平的强烈增加。
