期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 101, 期 3, 页码 1263-1273出版社
ENDOCRINE SOC
DOI: 10.1210/jc.2015-3054
关键词
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资金
- Helsinki University Hospital Research Funds
- Novo Nordisk Foundation
- Diabetes Research Foundation
- Jalmari and Rauha Ahokas Foundation
- Finnish Foundation for Cardivascular Research
- Academy of Finland [266286, 272376, 285963]
- Emil Aaltonen Foundatin
- Orion-Farmos Research Foundation
- Maud Kuistila Foumdation
- Finnish Medical Foundation
- Biocentrum Helsinki
- Sigrid Juselius Foundation
- Academy of Finland (AKA) [266286, 266286] Funding Source: Academy of Finland (AKA)
- Novo Nordisk Fonden [NNF10OC1013354] Funding Source: researchfish
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.
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