Sengenes C, Stich V, Berlan M, Hejnova J, Lafontan M, Pariskova Z, Galitzky J
INSERM Unité 317, Laboratory of Medical and Clinical Pharmacology, Faculty of Medicine, Toulouse, France.
Int J Obes Relat Metab Disord. 2002 Jan;26(1):24-32. doi: 10.1038/sj.ijo.0801845.
We recently demonstrated that natriuretic peptides (NP) are involved in a pathway inducing lipolysis in human adipose tissue. Atrial NP (ANP) and brain NP (BNP) operate via a cGMP-dependent pathway which does not involve phosphodiesterase-3B inhibition or cAMP. The study was performed to evaluate the effect of ANP on lipid mobilization in obese women and secondly to examine the possible effect of a low-calorie diet (LCD) on the lipolytic response of subcutaneous abdominal fat cells to NP and on the lipid mobilization induced by ANP infusion (1 microg/m(2) min for 60 min).
Ten obese women from 40.5+/-3.4 y old were selected for this study. Their body weight was 96.4+/-5.7 kg and their BMI was 35.3+/-1.7 kg/m(2). They received a 2.5-2.9 MJ/day formula diet for 28 days.
Before and during the LCD, an adipose tissue biospy was performed for in vitro studies and, moreover, ANP was perfused i.v. to evaluate its lipid mobilizing action in toto and in situ in subcutaneous abdominal adipose tissue (SCAAT) using microdialysis.
The lipolytic effects of isoproterenol, ANP, BNP and bromo-cGMP (an analogue of cGMP) on fat cells increased by about 80-100% during LCD. The lipid mobilization during i.v. ANP infusion, assessed by plasma non-esterified fatty acids (NEFA) increase was enhanced during the LCD. However, during LCD, ANP infusion induced a biphasic effect on glycerol concentration in plasma and interstitial fluid of SCAAT; a significant increase was observed in glycerol levels during the first 30 min infusion period, followed by a steady decrease. The concentration of glycerol was lower during the post-infusion period than during the baseline period. This effect was stronger in obese subjects submitted to the LCD with a low-carbohydrate composition. Other plasma parameters were weakly increased (noradrenaline) or not modified (insulin, glucose) by ANP infusion and no difference was found before and during LCD treatment.
The present study shows that NP are powerful lipolytic agents in subcutaneous fat cells and that both isoproterenol- and NP-induced lipolysis increase during LCD, in obese women. These changes seem to be associated with an improvement of the lipolytic pathway at a post-receptor level. Moreover, i.v. administration of ANP induced a lipid mobilizing effect which was enhanced by a LCD in these objects.
我们最近证明利钠肽(NP)参与诱导人体脂肪组织脂肪分解的途径。心房利钠肽(ANP)和脑利钠肽(BNP)通过不涉及磷酸二酯酶-3B抑制或环磷酸腺苷(cAMP)的环磷酸鸟苷(cGMP)依赖性途径发挥作用。本研究旨在评估ANP对肥胖女性脂质动员的影响,其次研究低热量饮食(LCD)对皮下腹部脂肪细胞对NP的脂解反应以及对ANP输注(1微克/平方米·分钟,持续60分钟)诱导的脂质动员的可能影响。
本研究选取了10名年龄在40.5±3.4岁的肥胖女性。她们的体重为96.4±5.7千克,体重指数(BMI)为35.3±1.7千克/平方米。她们接受了为期28天、每天2.5 - 2.9兆焦耳的配方饮食。
在LCD之前和期间,进行脂肪组织活检以进行体外研究,此外,静脉灌注ANP,使用微透析评估其在皮下腹部脂肪组织(SCAAT)中整体和原位的脂质动员作用。
在LCD期间,异丙肾上腺素、ANP、BNP和溴化cGMP(cGMP类似物)对脂肪细胞的脂解作用增加了约80 - 100%。通过血浆非酯化脂肪酸(NEFA)增加评估的静脉输注ANP期间的脂质动员在LCD期间增强。然而,在LCD期间,ANP输注对SCAAT血浆和组织间液中甘油浓度产生双相作用;在输注的前30分钟期间甘油水平显著增加,随后稳定下降。输注后期间甘油浓度低于基线期。在接受低碳水化合物组成的LCD的肥胖受试者中这种作用更强。ANP输注对其他血浆参数(去甲肾上腺素)的影响微弱增加,(胰岛素、葡萄糖)未改变,并且在LCD治疗之前和期间未发现差异。
本研究表明NP是皮下脂肪细胞中强大的脂解剂,并且在肥胖女性中,异丙肾上腺素和NP诱导的脂解在LCD期间均增加。这些变化似乎与受体后水平脂解途径的改善有关。此外,静脉注射ANP诱导脂质动员作用,在这些受试者中LCD可增强该作用。