Rydén M, Bäckdahl J, Petrus P, Thorell A, Gao H, Coue M, Langin D, Moro C, Arner P
Department of Medicine-H7, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Department of Surgery, Karolinska Institutet, Ersta Hospital, Stockholm, Sweden.
Int J Obes (Lond). 2016 Apr;40(4):714-20. doi: 10.1038/ijo.2015.222. Epub 2015 Oct 26.
Catecholamines and natriuretic peptides (NPs) are the only hormones with pronounced lipolytic effects in human white adipose tissue. Although catecholamine-induced lipolysis is well known to be impaired in obesity and insulin resistance, it is not known whether the effect of NPs is also altered.
Catecholamine- and atrial NP (ANP)-induced lipolysis was investigated in abdominal subcutaneous adipocytes in vitro and in situ by microdialysis.
In a cohort of 122 women, both catecholamine- and ANP-induced lipolysis in vitro was markedly attenuated in obesity (n=87), but normalized after substantial body weight loss (n=52). The impairment of lipolysis differed between the two hormones when expressing lipolysis per lipid weight, the ratio of stimulated over basal (spontaneous) lipolysis rate or per number of adipocytes. Thus, while the response to catecholamines was lower when expressed as the former two measures, it was higher when expressed per cell number, a consequence of the significantly larger fat cell size in obesity. In contrast, although ANP-induced lipolysis was also attenuated when expressed per lipid weight or the ratio stimulated/basal, it was similar between non-obese and obese subjects when expressed per cell number suggesting that the lipolytic effect of ANP may be even more sensitive to the effects of obesity than catecholamines. Obesity was characterized by a decrease in the protein expression of the signaling NP A receptor (NPRA) and a trend toward increased levels of the clearance receptor NPRC. The impairment in ANP-induced lipolysis observed in vitro was corroborated by microdialysis experiments in situ in a smaller cohort of lean and overweight men.
ANP- and catecholamine-induced lipolysis is reversibly attenuated in obesity. The pro-lipolytic effects of ANP are relatively more impaired compared with that of catecholamines, which may in part be due to specific changes in NP receptor expression.
儿茶酚胺和利钠肽（NPs）是人类白色脂肪组织中仅有的具有显著脂解作用的激素。尽管众所周知，儿茶酚胺诱导的脂解在肥胖和胰岛素抵抗中受损，但尚不清楚NPs的作用是否也会改变。
通过微透析在体外和原位研究腹部皮下脂肪细胞中儿茶酚胺和心房利钠肽（ANP）诱导的脂解。
在122名女性队列中，肥胖者（n = 87）体外儿茶酚胺和ANP诱导的脂解均明显减弱，但在体重显著减轻后恢复正常（n = 52）。当以每脂质重量、刺激与基础（自发）脂解速率之比或每脂肪细胞数来表示脂解时，两种激素的脂解受损情况有所不同。因此，以前两种指标表示时，对儿茶酚胺的反应较低，但以每细胞数表示时则较高，这是肥胖中脂肪细胞显著增大的结果。相比之下，尽管以每脂质重量或刺激/基础比值表示时，ANP诱导的脂解也减弱，但以每细胞数表示时，非肥胖和肥胖受试者之间相似，这表明ANP的脂解作用可能比儿茶酚胺对肥胖的影响更敏感。肥胖的特征是信号利钠肽A受体（NPRA）的蛋白表达降低，清除受体NPRC水平有升高趋势。在较小的瘦和超重男性队列中进行的原位微透析实验证实了体外观察到的ANP诱导脂解的受损情况。
肥胖时ANP和儿茶酚胺诱导的脂解可逆性减弱。与儿茶酚胺相比，ANP的促脂解作用相对受损更严重，这可能部分归因于NP受体表达的特定变化。
