title: Selective enhancement of insulin sensitivity in the mature adipocyte is sufficient for systemic metabolic improvements.
abstract: Dysfunctional adipose tissue represents a hallmark of type 2 diabetes and systemic insulin resistance, characterized by fibrotic deposition of collagens and increased immune cell infiltration within the depots. Here we generate an inducible model of loss of function of the protein phosphatase and tensin homologue (PTEN), a phosphatase critically involved in turning off the insulin signal transduction cascade, to assess the role of enhanced insulin signalling specifically in mature adipocytes. These mice gain more weight on chow diet and short-term as well as long-term high-fat diet exposure. Despite the increase in weight, they retain enhanced insulin sensitivity, show improvements in oral glucose tolerance tests, display reduced adipose tissue inflammation and maintain elevated adiponectin levels. These improvements also lead to reduced hepatic steatosis and enhanced hepatic insulin sensitivity. Prolonging insulin action selectively in the mature adipocyte is therefore sufficient to maintain normal systemic metabolic homeostasis.
authors.affiliation: Department of Internal Medicine, Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-8549, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Morley
authors.affiliation: Department of Internal Medicine, Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-8549, USA.
authors.forename: Jonathan Y
authors.initials: JY
authors.lastname: Xia
authors.affiliation: Department of Internal Medicine, Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-8549, USA.|Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-8549, USA.
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D052242:Adiponectin / Q000097:blood*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D004734:Energy Metabolism; D055786:Gene Knockout Techniques; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation
chemical_list: D052242:Adiponectin; D007328:Insulin; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse