Resveratrol regulates human adipocyte number and function in a Sirt1-dependent manner.
BACKGROUND
Caloric restriction leads to retardation of the aging processes and to longer life in many organisms. This effect of caloric restriction can be mimicked by resveratrol, a natural plant product present in grapes and red wine, which is known as a potent activator of sirtuin 1 [silent mating type information regulation 2 homolog 1 (Sirt1)].


OBJECTIVE
One main effect of caloric restriction in mammals is a reduction of body fat from white adipose tissue. We sought to identify the effects of resveratrol on fat cell biology and to elucidate whether Sirt1 is involved in resveratrol-mediated changes.


METHODS
Human Simpson-Golabi-Behmel syndrome preadipocytes and adipocytes were used to study proliferation, adipogenic differentiation, glucose uptake, de novo lipogenesis, and adipokine secretion. Sirt1-deficient human preadipocytes were generated by using a lentiviral small hairpin RNA system to study the role of Sirt1 in resveratrol-mediated changes.


RESULTS
Resveratrol inhibited preadipocyte proliferation and adipogenic differentiation in a Sirt1-dependent manner. In human adipocytes, resveratrol stimulated basal and insulin-stimulated glucose uptake. De novo lipogenesis was inhibited in parallel with a down-regulation of lipogenic gene expression. Furthermore, resveratrol down-regulated the expression and secretion of interleukin-6 and interleukin-8. Sirt1 was only partially responsible for the regulation of resveratrol-mediated changes in adipokine secretion.


CONCLUSIONS
Taken together, our data suggest that resveratrol influences adipose tissue mass and function in a way that may positively interfere with the development of obesity-related comorbidities. Thus, our findings open up the new perspective that resveratrol-induced intracellular pathways could be a target for prevention or treatment of obesity-associated endocrine and metabolic adverse effects.
Fischer-Posovszky
Pamela
P
Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany.
Kukulus
Vera
V
Tews
Daniel
D
Unterkircher
Thomas
T
Debatin
Klaus-Michael
KM
Fulda
Simone
S
Wabitsch
Martin
M
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D000273:Adipose Tissue / Q000033:anatomy & histology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D031204:Caloric Restriction / Q000706:statistics & numerical data; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D018389:Codon, Nonsense; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers; D004261:DNA Replication; D005947:Glucose / Q000378:metabolism; D006801:Humans; D055029:Inverted Repeat Sequences; D012313:RNA / Q000235:genetics; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D027843:Vitis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018389:Codon, Nonsense; D016207:Cytokines; D017931:DNA Primers; D013267:Stilbenes; D012313:RNA; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D005947:Glucose; D000077185:Resveratrol; D013936:Thymidine