Pharmacological inhibition of adipose triglyceride lipase corrects high-fat diet-induced insulin resistance and hepatosteatosis in mice

Martina Schweiger (), Matthias Romauch, Renate Schreiber, Gernot F. Grabner, Sabrina Hütter, Petra Kotzbeck, Pia Benedikt, Thomas O. Eichmann, Sohsuke Yamada, Oskar Knittelfelder, Clemens Diwoky, Carina Doler, Nicole Mayer, Werner De Cecco, Rolf Breinbauer, Robert Zimmermann () and Rudolf Zechner ()
Additional contact information
Martina Schweiger: Institute of Molecular Biosciences, University of Graz
Matthias Romauch: Institute of Molecular Biosciences, University of Graz
Renate Schreiber: Institute of Molecular Biosciences, University of Graz
Gernot F. Grabner: Institute of Molecular Biosciences, University of Graz
Sabrina Hütter: Institute of Molecular Biosciences, University of Graz
Petra Kotzbeck: Institute of Molecular Biosciences, University of Graz
Pia Benedikt: Institute of Molecular Biosciences, University of Graz
Thomas O. Eichmann: Institute of Molecular Biosciences, University of Graz
Sohsuke Yamada: Institute of Molecular Biosciences, University of Graz
Oskar Knittelfelder: Institute of Molecular Biosciences, University of Graz
Clemens Diwoky: Institute of Molecular Biosciences, University of Graz
Carina Doler: Institute of Organic Chemistry, Graz University of Technology
Nicole Mayer: Institute of Organic Chemistry, Graz University of Technology
Werner De Cecco: Institute of Chemistry, University of Graz
Rolf Breinbauer: Institute of Organic Chemistry, Graz University of Technology
Robert Zimmermann: Institute of Molecular Biosciences, University of Graz
Rudolf Zechner: Institute of Molecular Biosciences, University of Graz

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: Abstract Elevated circulating fatty acids (FAs) contribute to the development of obesity-associated metabolic complications such as insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD). Hence, reducing adipose tissue lipolysis to diminish the mobilization of FAs and lower their respective plasma concentrations represents a potential treatment strategy to counteract obesity-associated disorders. Here we show that specific inhibition of adipose triglyceride lipase (Atgl) with the chemical inhibitor, Atglistatin, effectively reduces adipose tissue lipolysis, weight gain, IR and NAFLD in mice fed a high-fat diet. Importantly, even long-term treatment does not lead to lipid accumulation in ectopic tissues such as the skeletal muscle or heart. Thus, the severe cardiac steatosis and cardiomyopathy that is observed in genetic models of Atgl deficiency does not occur in Atglistatin-treated mice. Our data validate the pharmacological inhibition of Atgl as a potentially powerful therapeutic strategy to treat obesity and associated metabolic disorders.

Date: 2017
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/ncomms14859 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14859

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms14859

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().