title: Adipose-specific deletion of Src homology phosphatase 2 does not significantly alter systemic glucose homeostasis.
abstract: The SH2 domain-containing protein-tyrosine phosphatase Src homology phosphatase 2 (Shp2) has been implicated in a variety of growth factor signaling pathways, but its metabolic role in some peripheral insulin-responsive tissues remains unknown. To address the metabolic function of Shp2 in adipose tissue, we generated mice with adipose-specific Shp2 deletion using adiponectin-Cre transgenic mice. We then analyzed insulin sensitivity, glucose tolerance, and body mass in adipose-specific Shp2-deficient and control mice on regular chow and high-fat diet (HFD). Control mice on HFD exhibited increased Shp2 expression in various adipose depots compared with those on regular chow. Adiponectin-Cre mice enabled efficient and specific deletion of Shp2 in adipose tissue. However, adipose Shp2 deletion did not significantly alter body mass in mice on chow or HFD. In addition, mice with adipose Shp2 deletion exhibited comparable insulin sensitivity and glucose tolerance compared with controls. Consistent with this, basal and insulin-stimulated Erk and Akt phosphorylations were comparable in adipose tissue of Shp2-deficient and control mice. Our findings indicate that adipose-specific Shp2 deletion does not significantly alter systemic insulin sensitivity and glucose homeostasis.
authors.affiliation: Nutrition Department, University of California Davis, Davis, CA 95616, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Bettaieb
authors.forename: Kosuke
authors.initials: K
authors.lastname: Matsuo
authors.forename: Izumi
authors.initials: I
authors.lastname: Matsuo
authors.forename: Naoto
authors.initials: N
authors.lastname: Nagata
authors.forename: Samah
authors.initials: S
authors.lastname: Chahed
authors.forename: Siming
authors.initials: S
authors.lastname: Liu
authors.forename: Fawaz G
authors.initials: FG
authors.lastname: Haj
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics*; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D007328:Insulin; D051057:Proto-Oncogene Proteins c-akt; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D005947:Glucose