Weight Loss Is Associated With Increased NAD(+)/SIRT1 Expression But Reduced PARP Activity in White Adipose Tissue

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.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, White / metabolism*
  • Adult
  • Counseling
  • Cytokines / genetics
  • Cytokines / metabolism
  • Diet, Reducing
  • Down-Regulation
  • Female
  • Humans
  • Male
  • NAD / metabolism*
  • Nicotinamide Phosphoribosyltransferase / genetics
  • Nicotinamide Phosphoribosyltransferase / metabolism
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / therapy
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Signal Transduction / genetics
  • Sirtuin 1 / genetics*
  • Sirtuin 1 / metabolism
  • Sirtuins / genetics
  • Sirtuins / metabolism
  • Subcutaneous Fat / metabolism
  • Up-Regulation / genetics
  • Weight Loss / physiology*


  • Cytokines
  • NAD
  • Nicotinamide Phosphoribosyltransferase
  • nicotinamide phosphoribosyltransferase, human
  • Poly(ADP-ribose) Polymerases
  • SIRT1 protein, human
  • Sirtuin 1
  • Sirtuins