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Type of publication: Journal Article
Type of document: Full Paper

Year: 2017

Authors: Kaltenecker, D; Mueller, KM; Benedikt, P; Feiler, U; Themanns, M; Schlederer, M; Kenner, L; Schweiger, M; Haemmerle, G; Moriggl, R

Title: Adipocyte STAT5 deficiency promotes adiposity and impairs lipid mobilisation in mice.

Source: Diabetologia (60), 2 296-305.

Authors Vetmeduni Vienna:

Kaltenecker Doris
Kenner Lukas
Moriggl Richard
Müller Kristina
Themanns Madeleine

Vetmed Research Units
Institute of Pathology, Pathology of Laboratory Animals
Institute of Animal Breeding and Genetics, Unit for Functional Cancer Genomics

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.

Keywords Pubmed: 3T3-L1 Cells
Blotting, Western
Chromatin Immunoprecipitation
Electrophoretic Mobility Shift Assay
Insulin Resistancegeneticsphysiology
Lipid Metabolismgeneticsphysiology
Lipid Mobilizationgeneticsphysiology
Quality of Life
Real-Time Polymerase Chain Reaction
STAT5 Transcription Factorgeneticsmetabolism

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