Moro Cédric, Berlan Michel, Lafontan Max
Inserm, U586, Unité de Recherche sur les Obésités, F-31432 Toulouse.
J Soc Biol. 2006;200(1):67-76. doi: 10.1051/jbio:2006009.
We have demonstrated a potent and specific lipolytic effect of natriuretic peptides (NP) in human and primates' fat cells. The lipolytic effect of NP is mediated through intracellular production of cGMP and activation of the cGMP-dependent kinase 1alpha. Local infusion of atrial-NP (ANP), directly within the subcutaneous adipose tissue through a microdialysis catheter, increases lipolysis and stimulates blood flow through its vasodilating effect in lean healthy men. This effect is blunted in overweight men and can be recovered by endurance training. Intravenous infusion of physiological doses of ANP induces lipid mobilization. Higher concentrations of ANP that are encountered during heart failure also stimulate lipid oxidation. ANP activates lipolysis and free fatty acids release from adipose tissue during endurance exercise. This effect is paradoxically amplified when exercise is performed under beta-blockade treatment, because of an enhanced cardiac release of ANP. No gender differences in ANP-induced lipid mobilization during exercise have been found. Heart failure is associated with high circulating levels of NP that could participate to the progression toward cachexia. On contrary, a negative correlation between NP levels and body mass index is found in obese persons. The molecular basis of this inverse correlation is not yet demonstrated from a functional standpoint. Further studies are needed to clearly define the pathophysiological role of NP in obesity and heart failure.
我们已经证明了利钠肽(NP)在人类和灵长类动物脂肪细胞中具有强大且特异的脂解作用。NP的脂解作用是通过细胞内cGMP的产生以及cGMP依赖性蛋白激酶1α的激活来介导的。通过微透析导管将心房利钠肽(ANP)直接局部注入皮下脂肪组织,可增加脂解作用,并通过其对健康瘦男性的血管舒张作用刺激血流。超重男性的这种作用减弱,而耐力训练可使其恢复。静脉输注生理剂量的ANP可诱导脂质动员。心力衰竭时出现的较高浓度的ANP也能刺激脂质氧化。在耐力运动期间,ANP可激活脂解作用并促进脂肪组织释放游离脂肪酸。当在β受体阻滞剂治疗下进行运动时,由于ANP从心脏的释放增加,这种作用会反常地增强。尚未发现运动期间ANP诱导的脂质动员存在性别差异。心力衰竭与循环中高水平的NP有关,这可能参与了恶病质的进展。相反,在肥胖者中发现NP水平与体重指数呈负相关。从功能角度来看,这种负相关的分子基础尚未得到证实。需要进一步研究来明确NP在肥胖和心力衰竭中的病理生理作用。