title: Adipocyte STAT5 deficiency promotes adiposity and impairs lipid mobilisation in mice.
abstract: Dysfunction of lipid metabolism in white adipose tissue can substantially interfere with health and quality of life, for example in obesity and associated metabolic diseases. Therefore, it is important to characterise pathways that regulate lipid handling in adipocytes and determine how they affect metabolic homeostasis. Components of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway are involved in adipocyte physiology and pathophysiology. However, the exact physiological importance of the STAT family member STAT5 in white adipose tissue is yet to be determined. Here, we aimed to delineate adipocyte STAT5 functions in the context of lipid metabolism in white adipose tissue.
  
  
  
  We generated an adipocyte specific knockout of Stat5 in mice using the Adipoq-Cre recombinase transgene followed by in vivo and in vitro biochemical and molecular studies.
  
  
  
  Adipocyte-specific deletion of Stat5 resulted in increased adiposity, while insulin resistance and gluconeogenic capacity was decreased, indicating that glucose metabolism can be improved by interfering with adipose STAT5 function. Basal lipolysis and fasting-induced lipid mobilisation were diminished upon STAT5 deficiency, which coincided with reduced levels of the rate-limiting lipase of triacylglycerol hydrolysis, adipose triglyceride lipase (ATGL, encoded by Pnpla2) and its coactivator comparative gene identification 58 (CGI-58). In a mechanistic analysis, we identified a functional STAT5 response element within the Pnpla2 promoter, indicating that Pnpla2 is transcriptionally regulated by STAT5.
  
  
  
  Our findings reveal an essential role for STAT5 in maintaining lipid homeostasis in white adipose tissue and provide a rationale for future studies into the potential of STAT5 manipulation to improve outcomes in metabolic diseases.
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.|Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210, Vienna, Austria.
authors.forename: Doris
authors.initials: D
authors.lastname: Kaltenecker
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.|Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210, Vienna, Austria.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Mueller
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors.forename: Pia
authors.initials: P
authors.lastname: Benedikt
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors.forename: Ursula
authors.initials: U
authors.lastname: Feiler
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.|Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210, Vienna, Austria.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Themanns
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.|Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Schlederer
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.|Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.|Unit of Pathology of Laboratory Animals, University of Veterinary Medicine Vienna, Vienna, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Kenner
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Schweiger
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors.forename: Guenter
authors.initials: G
authors.lastname: Haemmerle
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria. richard.moriggl@lbicr.lbg.ac.at.|Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210, Vienna, Austria. richard.moriggl@lbicr.lbg.ac.at.|Medical University of Vienna, Vienna, Austria. richard.moriggl@lbicr.lbg.ac.at.
authors.forename: Richard
authors.initials: R
authors.lastname: Moriggl
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D050154:Adiposity / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology; D008053:Lipid Mobilization / Q000235:genetics / Q000502:physiology; D008066:Lipolysis / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D011788:Quality of Life; D060888:Real-Time Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D050799:STAT5 Transcription Factor; D005947:Glucose
keywords: Adipose tissue; Energy metabolism; Lipolysis; STAT5