Decreased adipocyte glucose transporter 4 (GLUT4) and aquaglyceroporin-7 (AQP7) in adults with morbid obesity: possible early markers of metabolic dysfunction
Morbid obesity (BMI > 40) is often accompanied by metabolic disorders. In adipose tissue, serine/threonine kinase PKBβ/AktΙΙ plays a role in glucose uptake, mediated by glucose transporter 4 (GLUT4). The insulin pathway also affects aquaglyceroporin-7 (AQP7), which mediates lipolysis-derived glycerol efflux into the bloodstream. The aim of our study was to investigate the molecular mechanisms in adipocytes of adults with morbid obesity that may lead to insulin resistance (IR) and diabetes mellitus type 2 (DM2) in morbid obesity.
Primary in vitro adipocyte cultures were developed from surgical biopsies from visceral (Visc), abdominal (Sub), and gluteal subcutaneous (Glut) fat depots, from 20 lean adults and 36 adults with morbid obesity (OB), divided into two groups: 20 without (MOW) and 16 with DM2 (MODM). mRNA and protein expression (PE) of AktΙΙ, AQP7, and GLUT4 were studied with RT-PCR and Western immunoblotting (WI), respectively.
The PE of (1) AktII and basal phosphorylated AktII (pAktII) showed no difference within the groups, (2) the 37 kDa and 34 kDa isoforms of AQP7 were decreased in Visc/Sub from OB/MOW/MODM, (3) GLUT4 was decreased in Visc/Sub from OB/MOW/MODM, and (4) the 34 kDa isoform of AQP7 was decreased in Sub of MODM compared with MOW.
Decreased 37 kDa (presented in this study as a novel isoform) and 34 kDa isoforms of AQP7 in MOW and MODM may cause reduced lipolysis, enhancement of adipocyte hypertrophy, and impairment of insulin, signaling possibly reflected by low GLUT4 expression. This may potentially cause systemic IR, since decreased adipose GLUT4 expression may affect whole-body insulin sensitivity, increasing the risk for DM2. Furthermore, decreased subcutaneous AQP7 34 kDa could represent an early marker of IR.
KeywordsObesity GLUT4 AktII AQP7 Adipocytes
Funding was provided by the University of Patras, School of Medicine, Patras, Greece.
Compliance with ethical standards
Informed consent was obtained from all subjects. The study was approved by the Ethical Committee of the University Hospital of Patras, Greece.
Conflict of interest
The authors declare that they have no conflict of interest.
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