体重减轻与白色脂肪组织中NAD(+)/SIRT1表达增加但PARP活性降低有关。
Weight Loss Is Associated With Increased NAD(+)/SIRT1 Expression But Reduced PARP Activity in White Adipose Tissue.
作者信息
Rappou Elisabeth, Jukarainen Sakari, Rinnankoski-Tuikka Rita, Kaye Sanna, Heinonen Sini, Hakkarainen Antti, Lundbom Jesper, Lundbom Nina, Saunavaara Virva, Rissanen Aila, Virtanen Kirsi A, Pirinen Eija, Pietiläinen Kirsi H
机构信息
Obesity Research Unit (E.R., S.J., S.K., S.H., A.R., K.H.P.), Research Programs Unit, University of Helsinki, 00014 Helsinki, Finland; Research Program for Molecular Neurology (R.R.-T., E.P.), University of Helsinki, 00014 Helsinki, Finland; Helsinki Medical Imaging Center (A.H., J.L., N.L.), Radiology, University of Helsinki, 00290 Helsinki, Finland; Institute for Clinical Diabetology (J.L.), German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, 40225 Düsseldorf, Germany; Turku Positron Emission Tomography Center (V.S., K.A.V.), Turku University Hospital and University of Turku, 20521 Turku, Finland; Institute for Molecular Medicine Finland (K.H.P.), Institute for Molecular Medicine Finland, University of Helsinki, 00014 Helsinki, Finland; Endocrinology (K.H.P.), Abdominal Center, Helsinki University Hospital, University of Helsinki, 00014 Helsinki, Finland.
出版信息
J Clin Endocrinol Metab. 2016 Mar;101(3):1263-73. doi: 10.1210/jc.2015-3054. Epub 2016 Jan 13.
CONTEXT
Sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs) are 2 important nicotinamide adenine dinucleotide (NAD)(+)-dependent enzyme families with opposing metabolic effects. Energy shortage increases NAD(+) biosynthesis and SIRT activity but reduces PARP activity in animals. Effects of energy balance on these pathways in humans are unknown.
OBJECTIVE
We compared NAD(+)/SIRT pathway expressions and PARP activities in sc adipose tissue (SAT) between lean and obese subjects and investigated their change in the obese subjects during a 12-month weight loss.
DESIGN, SETTING AND PARTICIPANTS: SAT biopsies were obtained from 19 clinically healthy obese subjects (mean ± SE body mass index, 34.6 ± 2.7 kg/m(2)) during a weight-loss intervention (0, 5, and 12 mo) and from 19 lean reference subjects (body mass index, 22.7 ± 1.1 kg/m(2)) at baseline.
MAIN OUTCOME MEASURES
SAT mRNA expressions of SIRTs 1-7 and the rate-limiting gene in NAD(+) biosynthesis, nicotinamide phosphoribosyltransferase (NAMPT) were measured by Affymetrix, and total PARP activity by ELISA kit.
RESULTS
SIRT1, SIRT3, SIRT7, and NAMPT expressions were significantly lower, whereas total PARP activity was increased in obese compared with lean subjects. SIRT1 and NAMPT expressions increased in obese subjects between 0 and 5 months, after a mean weight loss of 11.7%. In subjects who continued to lose weight between 5 and 12 months, SIRT1 expression increased progressively, whereas in subjects with weight regain, SIRT1 reverted to baseline levels. PARP activity significantly decreased in all subjects upon weight loss.
CONCLUSIONS
Calorie restriction is an attractive strategy to improve the NAD(+)/SIRT pathway and decrease PARPs in SAT in human obesity.
背景
沉默调节蛋白（SIRTs）和聚（ADP - 核糖）聚合酶（PARPs）是两个重要的烟酰胺腺嘌呤二核苷酸（NAD）（+）依赖性酶家族，具有相反的代谢作用。能量短缺会增加动物体内NAD（+）的生物合成和SIRT活性，但会降低PARP活性。能量平衡对人类这些途径的影响尚不清楚。
目的
我们比较了瘦人和肥胖受试者皮下脂肪组织（SAT）中NAD（+）/SIRT途径的表达和PARP活性，并研究了肥胖受试者在12个月体重减轻期间这些指标的变化。
设计、地点和参与者：在体重减轻干预期间（0、5和12个月），从19名临床健康的肥胖受试者（平均±标准误体重指数，34.6±2.7kg/m²）获取SAT活检样本，并在基线时从19名瘦对照受试者（体重指数，22.7±1.1kg/m²）获取样本。
主要观察指标
通过Affymetrix检测SIRTs 1 - 7的SAT mRNA表达以及NAD（+）生物合成中的限速基因烟酰胺磷酸核糖基转移酶（NAMPT），并通过ELISA试剂盒检测总PARP活性。
结果
与瘦人相比，肥胖受试者的SIRT1、SIRT3、SIRT7和NAMPT表达显著降低，而总PARP活性增加。肥胖受试者在0至5个月期间，平均体重减轻11.7%后，SIRT1和NAMPT表达增加。在5至12个月继续减肥的受试者中，SIRT1表达逐渐增加，而在体重反弹的受试者中，SIRT1恢复到基线水平。所有受试者体重减轻后PARP活性显著降低。
结论
热量限制是改善人类肥胖中SAT的NAD（+）/SIRT途径并降低PARP的一种有吸引力的策略。
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