Pancreatic fat cells of humans with type 2 diabetes display reduced adipogenic and lipolytic activity

  • Morgana Barroso Oquendo
    German Center for Diabetes Research (DZD e.V.), Tübingen, Germany
  • Dorothea Siegel-Axel
    German Center for Diabetes Research (DZD e.V.), Tübingen, Germany
  • Felicia Gerst
    German Center for Diabetes Research (DZD e.V.), Tübingen, Germany
  • Estela Lorza-Gil
    German Center for Diabetes Research (DZD e.V.), Tübingen, Germany
  • Anja Moller
    German Center for Diabetes Research (DZD e.V.), Tübingen, Germany
  • Robert Wagner
    German Center for Diabetes Research (DZD e.V.), Tübingen, Germany
  • Jürgen Machann
    German Center for Diabetes Research (DZD e.V.), Tübingen, Germany
  • Falko Fend
    Institute of Pathology and Neuropathology, University Hospital of Eberhard-Karls-University Tübingen, Tübingen, Germany
  • Alfred Königsrainer
    Department of General, Visceral and Transplant Surgery, University Hospital of Eberhard-Karls-University Tübingen, Tübingen, Germany
  • Martin Heni
    German Center for Diabetes Research (DZD e.V.), Tübingen, Germany
  • Hans-Ulrich Häring
    German Center for Diabetes Research (DZD e.V.), Tübingen, Germany
  • Susanne Ullrich
    German Center for Diabetes Research (DZD e.V.), Tübingen, Germany
  • Andreas L. Birkenfeld
    German Center for Diabetes Research (DZD e.V.), Tübingen, Germany

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<jats:p> Obesity, especially visceral fat accumulation, increases the risk of type 2 diabetes (T2D). The purpose of this study was to investigate the impact of T2D on the pancreatic fat depot. Pancreatic fat pads from 17 partial pancreatectomized patients (PPP) were collected, pancreatic preadipocytes isolated, and in vitro differentiated. Patients were grouped using HbA1c into normal glucose tolerant (NGT), prediabetic (PD), and T2D. Transcriptome profiles of preadipocytes and adipocytes were assessed by RNAseq. Insulin sensitivity was estimated by quantifying AKT phosphorylation on Western blots. Lipogenic capacity was assessed with oil red O staining, lipolytic activity via fatty acid release. Secreted factors were measured using ELISA. Comparative transcriptome analysis of preadipocytes and adipocytes indicates defective upregulation of genes governing adipogenesis ( NR1H3), lipogenesis ( FASN, SCD, ELOVL6, and FADS1), and lipolysis ( LIPE) during differentiation of cells from T2D–PPP. In addition, the ratio of leptin/adiponectin mRNA was higher in T2D than in NGT–PPP. Preadipocytes and adipocytes of NGT–PPP were more insulin sensitive than T2D–PPP cells in regard to AKT phosphorylation. Triglyceride accumulation was similar in NGT and T2D adipocytes. Despite a high expression of the receptors NPR1 and NPR2 in NGT and T2D adipocytes, lipolysis was stimulated by ANP 1.74-fold in NGT cells only. This stimulation was further increased by the PDE5 inhibitor dipyridamole (3.09-fold). Dipyridamole and forskolin increased lipolysis receptor independently 1.88-fold and 1.48-fold, respectively, solely in NGT cells. In conclusion, the metabolic status persistently affects differentiation and lipolysis of pancreatic adipocytes. These alterations could aggravate the development of T2D. </jats:p>

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