PMID- 26015978
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150527
LR  - 20201001
IS  - 2329-0501 (Print)
IS  - 2329-0501 (Electronic)
IS  - 2329-0501 (Linking)
VI  - 1
DP  - 2014
TI  - AAV8-mediated Sirt1 gene transfer to the liver prevents high carbohydrate 
      diet-induced nonalcoholic fatty liver disease.
PG  - 14039
LID - 10.1038/mtm.2014.39 [doi]
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disease 
      worldwide, and evidence suggests that it promotes insulin resistance and type 2 
      diabetes. Caloric restriction (CR) is the only available strategy for NAFLD 
      treatment. The protein deacetylase Sirtuin1 (SIRT1), which is activated by CR, 
      increases catabolic metabolism and decreases lipogenesis and inflammation, both 
      involved in the development of NAFLD. Here we show that adeno-associated viral 
      vectors of serotype 8 (AAV8)-mediated liver-specific Sirt1 gene transfer prevents 
      the development of NAFLD induced by a high carbohydrate (HC) diet. Long-term 
      hepatic SIRT1 overexpression led to upregulation of key hepatic genes involved in 
      beta-oxidation, prevented HC diet-induced lipid accumulation and reduced liver 
      inflammation. AAV8-Sirt1-treated mice showed improved insulin sensitivity, 
      increased oxidative capacity in skeletal muscle and reduced white adipose tissue 
      inflammation. Moreover, HC feeding induced leptin resistance, which was also 
      attenuated in AAV8-Sirt1-treated mice. Therefore, AAV-mediated gene transfer to 
      overexpress SIRT1 specifically in the liver may represent a new gene therapy 
      strategy to counteract NAFLD and related diseases such as type 2 diabetes.
FAU - Vila, Laia
AU  - Vila L
AD  - Center of Animal Biotechnology and Gene Therapy, School of Veterinary Medicine, 
      Universitat Autonoma de Barcelona , Bellaterra, Spain ; Department of 
      Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat 
      Autonoma de Barcelona , Bellaterra, Spain ; Centro de Investigacion Biomedica en 
      Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM) , Barcelona, 
      Spain.
FAU - Elias, Ivet
AU  - Elias I
AD  - Center of Animal Biotechnology and Gene Therapy, School of Veterinary Medicine, 
      Universitat Autonoma de Barcelona , Bellaterra, Spain ; Department of 
      Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat 
      Autonoma de Barcelona , Bellaterra, Spain ; Centro de Investigacion Biomedica en 
      Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM) , Barcelona, 
      Spain.
FAU - Roca, Carles
AU  - Roca C
AD  - Center of Animal Biotechnology and Gene Therapy, School of Veterinary Medicine, 
      Universitat Autonoma de Barcelona , Bellaterra, Spain ; Department of 
      Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat 
      Autonoma de Barcelona , Bellaterra, Spain ; Centro de Investigacion Biomedica en 
      Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM) , Barcelona, 
      Spain.
FAU - Ribera, Albert
AU  - Ribera A
AD  - Center of Animal Biotechnology and Gene Therapy, School of Veterinary Medicine, 
      Universitat Autonoma de Barcelona , Bellaterra, Spain ; Department of 
      Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat 
      Autonoma de Barcelona , Bellaterra, Spain ; Centro de Investigacion Biomedica en 
      Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM) , Barcelona, 
      Spain.
FAU - Ferre, Tura
AU  - Ferre T
AD  - Center of Animal Biotechnology and Gene Therapy, School of Veterinary Medicine, 
      Universitat Autonoma de Barcelona , Bellaterra, Spain ; Centro de Investigacion 
      Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM) , 
      Barcelona, Spain.
FAU - Casellas, Alba
AU  - Casellas A
AD  - Center of Animal Biotechnology and Gene Therapy, School of Veterinary Medicine, 
      Universitat Autonoma de Barcelona , Bellaterra, Spain ; Centro de Investigacion 
      Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM) , 
      Barcelona, Spain.
FAU - Lage, Ricardo
AU  - Lage R
AD  - Center of Animal Biotechnology and Gene Therapy, School of Veterinary Medicine, 
      Universitat Autonoma de Barcelona , Bellaterra, Spain ; Department of 
      Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat 
      Autonoma de Barcelona , Bellaterra, Spain.
FAU - Franckhauser, Sylvie
AU  - Franckhauser S
AD  - Center of Animal Biotechnology and Gene Therapy, School of Veterinary Medicine, 
      Universitat Autonoma de Barcelona , Bellaterra, Spain ; Centro de Investigacion 
      Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM) , 
      Barcelona, Spain.
FAU - Bosch, Fatima
AU  - Bosch F
AD  - Center of Animal Biotechnology and Gene Therapy, School of Veterinary Medicine, 
      Universitat Autonoma de Barcelona , Bellaterra, Spain ; Department of 
      Biochemistry and Molecular Biology, School of Veterinary Medicine, Universitat 
      Autonoma de Barcelona , Bellaterra, Spain ; Centro de Investigacion Biomedica en 
      Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM) , Barcelona, 
      Spain.
LA  - eng
PT  - Journal Article
DEP - 20141001
PL  - United States
TA  - Mol Ther Methods Clin Dev
JT  - Molecular therapy. Methods & clinical development
JID - 101624857
PMC - PMC4362360
EDAT- 2014/01/01 00:00
MHDA- 2014/01/01 00:01
PMCR- 2014/10/01
CRDT- 2015/05/28 06:00
PHST- 2014/03/19 00:00 [received]
PHST- 2014/06/26 00:00 [revised]
PHST- 2014/07/18 00:00 [accepted]
PHST- 2015/05/28 06:00 [entrez]
PHST- 2014/01/01 00:00 [pubmed]
PHST- 2014/01/01 00:01 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - S2329-0501(16)30106-1 [pii]
AID - 10.1038/mtm.2014.39 [doi]
PST - epublish
SO  - Mol Ther Methods Clin Dev. 2014 Oct 1;1:14039. doi: 10.1038/mtm.2014.39. 
      eCollection 2014.