Lafontan Max, Moro Cédric, Berlan Michel, Crampes François, Sengenes Coralie, Galitzky Jean
Inserm (Institut National de la Santé et de la Recherche Médicale) U858, I2MR-Institut de Médecine Moléculaire de Rangueil, BP 84225, Toulouse CEDEX 4, France.
Trends Endocrinol Metab. 2008 May-Jun;19(4):130-7. doi: 10.1016/j.tem.2007.11.006. Epub 2008 Mar 11.
Human fat cell lipolysis was, until recently, thought to be mediated exclusively by a cAMP-dependent protein kinase (PKA)-regulated pathway under the control of catecholamines and insulin. We have shown that atrial- and B-type natriuretic peptides (ANP and BNP respectively) stimulate lipolysis in human fat cells through a cGMP-dependent protein kinase (PKG) signaling pathway independent of cAMP production and PKA activity. Pharmacological or physiological (exercise) increases in plasma ANP levels stimulate lipid mobilization in humans. This pathway becomes important during chronic treatment with beta-adrenoceptor antagonists, which inhibit catecholamine-induced lipolysis but enhance cardiac ANP release. These findings have metabolic implications and point to potential problems when natriuretic peptide secretion is altered or during therapeutic use of recombinant BNP.
直到最近，人们还认为人类脂肪细胞的脂解作用完全由儿茶酚胺和胰岛素控制下的一种依赖环磷酸腺苷（cAMP）的蛋白激酶（PKA）调节途径介导。我们已经表明，心房利钠肽和B型利钠肽（分别为ANP和BNP）通过一种不依赖cAMP生成和PKA活性的依赖环磷酸鸟苷（cGMP）的蛋白激酶（PKG）信号通路刺激人类脂肪细胞的脂解作用。血浆ANP水平的药理学或生理学（运动）升高会刺激人类的脂质动员。在使用β-肾上腺素能受体拮抗剂进行长期治疗期间，该途径变得很重要，β-肾上腺素能受体拮抗剂会抑制儿茶酚胺诱导的脂解作用，但会增强心脏ANP的释放。这些发现具有代谢意义，并指出了当利钠肽分泌改变时或在重组BNP的治疗应用期间可能存在的问题。
