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

• Published in: The journal of clinical endocrinology and metabolism Vol. 101; no. 3; pp. 1263 - 1273
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.03.2016; Copyright by The Endocrine Society
• Subjects: Adipose tissue; Adipose Tissue, White - metabolism; Adult; Biopsy; Biosynthesis; Body fat; Body mass index; Body weight loss; Counseling; Cytokines - genetics; Cytokines - metabolism; Diet, Reducing; Down-Regulation; Energy balance; Enzyme-linked immunosorbent assay; Female; Humans; Male; mRNA; NAD; NAD - metabolism; Nicotinamide phosphoribosyltransferase; Nicotinamide Phosphoribosyltransferase - genetics; Nicotinamide Phosphoribosyltransferase - metabolism; Nutrient deficiency; Obesity; Obesity - genetics; Obesity - metabolism; Obesity - therapy; Phosphoribosyltransferase; Poly(ADP-ribose); Poly(ADP-ribose) polymerase; Poly(ADP-ribose) Polymerases - metabolism; Signal Transduction - genetics; SIRT1 protein; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Sirtuins; Sirtuins - genetics; Sirtuins - metabolism; Subcutaneous Fat - metabolism; Up-Regulation - genetics; Weight Loss - physiology
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2015-3054

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/m2) during a weight-loss intervention (0, 5, and 12 mo) and from 19 lean reference subjects (body mass index, 22.7 ± 1.1 kg/m2) 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.