SpringerLink
Log in

Decreased adipocyte glucose transporter 4 (GLUT4) and aquaglyceroporin-7 (AQP7) in adults with morbid obesity: possible early markers of metabolic dysfunction

  • Original Article
  • Published:
Hormones Aims and scope Submit manuscript

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. James WP (2008) The epidemiology of obesity: the size of the problem. J Intern Med 263:336–352

    Article  CAS  PubMed  Google Scholar 

  2. Goossens GH (2008) The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance. Physiol Behav 94:206–218

    Article  CAS  PubMed  Google Scholar 

  3. Sun K, Kusminski CM, Scherer PE (2011) Adipose tissue remodeling and obesity. J Clin Invest 121:2094–2101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kohn AD, Summers SA, Birnbaum MJ, Roth RA (1996) Expression of a constitutively active Akt Ser/Thr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation. J Biol Chem 271:31372–31378

    Article  CAS  PubMed  Google Scholar 

  5. Su X, Lodhi IJ, Saltiel AR, Stahl PD (2006) Insulin-stimulated interaction between insulin receptor substrate 1 and p85alpha and activation of protein kinase B/Akt require Rab5. J Biol Chem 281:27982–27990

    Article  CAS  PubMed  Google Scholar 

  6. Deepa SS, Dong LQ (2009) APPL1: role in adiponectin signaling and beyond. Am J Physiol Endocrinol Metab 296:E22–E36

    Article  CAS  PubMed  Google Scholar 

  7. Collins JM, Neville MJ, Pinnick KE, Hodson L, Ruyter B, van Dijk TH et al (2011) De novo lipogenesis in the differentiating human adipocyte can provide all fatty acids necessary for maturation. J Lipid Res 52:1683–1692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kahn BB, Rossetti L, Lodish HF, Charron MJ (1991) Decreased in vivo glucose uptake but normal expression of GLUT1 and GLUT4 in skeletal muscle of diabetic rats. J Clin Invest 87:2197–2206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Abel ED, Peroni O, Kim JK, Kim YB, Boss O, Hadro E et al (2001) Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature. 409:729–733

    Article  CAS  PubMed  Google Scholar 

  10. Bernat-Karpinska M, Czech A, Piatkiewicz P, Wierzbicki P, Gorski A (2010) Cellular glucose transport disturbances as a marker of the pre-diabetic state - pathogenetic and clinical significance of the assessment of GLUT4 expression. Endokrynol Pol 61:269–274

    CAS  PubMed  Google Scholar 

  11. Rodriguez A, Catalan V, Gomez-Ambrosi J, Fruhbeck G (2011) Aquaglyceroporins serve as metabolic gateways in adiposity and insulin resistance control. Cell Cycle 10:1548–1556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gambert S, Helies-Toussaint C, Grynberg A (2007) Extracellular glycerol regulates the cardiac energy balance in a working rat heart model. Am J Physiol Heart Circ Physiol 292:H1600–H1606

    Article  CAS  PubMed  Google Scholar 

  13. Matsumura K, Chang BH, Fujimiya M, Chen W, Kulkarni RN, Eguchi Y et al (2007) Aquaporin 7 is a beta-cell protein and regulator of intraislet glycerol content and glycerol kinase activity, beta-cell mass, and insulin production and secretion. Mol Cell Biol 27:6026–6037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Rodriguez A, Catalan V, Gomez-Ambrosi J, Garcia-Navarro S, Rotellar F, Valenti V et al (2011) Insulin- and leptin-mediated control of aquaglyceroporins in human adipocytes and hepatocytes is mediated via the PI3K/Akt/mTOR signaling cascade. J Clin Endocrinol Metab 96:E586–E597

    Article  CAS  PubMed  Google Scholar 

  15. Marrades MP, Milagro FI, Martinez JA, Moreno-Aliaga MJ (2006) Differential expression of aquaporin 7 in adipose tissue of lean and obese high fat consumers. Biochem Biophys Res Commun 339:785–789

    Article  CAS  PubMed  Google Scholar 

  16. Oikonomou E, Kostopoulou E, Rojas-Gil AP, Georgiou G, Spiliotis BE (2018) Adipocyte aquaporin 7 (AQP7) expression in lean children and children with obesity. Possible involvement in molecular mechanisms of childhood obesity. J Pediatr Endocrinol Metab

  17. Lebeck J, Ostergard T, Rojek A, Fuchtbauer EM, Lund S, Nielsen S et al (2012) Gender-specific effect of physical training on AQP7 protein expression in human adipose tissue. Acta Diabetol 49(Suppl 1):S215–S226

    Article  PubMed  Google Scholar 

  18. Shen FX, Gu X, Pan W, Li WP, Li W, Ye J et al (2012) Over-expression of AQP7 contributes to improve insulin resistance in adipocytes. Exp Cell Res 318:2377–2384

    Article  CAS  PubMed  Google Scholar 

  19. Laforenza U, Gastaldi G, Grazioli M, Cova E, Tritto S, Faelli A et al (2005) Expression and immunolocalization of aquaporin-7 in rat gastrointestinal tract. Biol Cell 97:605–613

    Article  CAS  PubMed  Google Scholar 

  20. McAuley KA, Williams SM, Mann JI, Walker RJ, Lewis-Barned NJ, Temple LA et al (2001) Diagnosing insulin resistance in the general population. Diabetes Care 24:460–464

    Article  CAS  PubMed  Google Scholar 

  21. Mifflin MD, St Jeor ST, Hill LA, Scott BJ, Daugherty SA, Koh YO (1990) A new predictive equation for resting energy expenditure in healthy individuals. Am J Clin Nutr 51:241–247

    Article  CAS  PubMed  Google Scholar 

  22. Karvela A, Rojas-Gil AP, Samkinidou E, Papadaki H, Pappa A, Georgiou G et al (2010) Endocannabinoid (EC) receptor, CB1, and EC enzymes’ expression in primary adipocyte cultures of lean and obese pre-pubertal children in relation to adiponectin and insulin. J Pediatr Endocrinol Metab 23:1011–1024

    Article  CAS  PubMed  Google Scholar 

  23. Kurowski TG, Lin Y, Luo Z, Tsichlis PN, Buse MG, Heydrick SJ et al (1999) Hyperglycemia inhibits insulin activation of Akt/protein kinase B but not phosphatidylinositol 3-kinase in rat skeletal muscle. Diabetes. 48:658–663

    Article  CAS  PubMed  Google Scholar 

  24. Carvalho E, Eliasson B, Wesslau C, Smith U (2000) Impaired phosphorylation and insulin-stimulated translocation to the plasma membrane of protein kinase B/Akt in adipocytes from type II diabetic subjects. Diabetologia. 43:1107–1115

    Article  CAS  PubMed  Google Scholar 

  25. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 28:412–419

    Article  CAS  Google Scholar 

  26. Manolopoulos KN, Karpe F, Frayn KN (2010) Gluteofemoral body fat as a determinant of metabolic health. Int J Obes 34:949–959

    Article  CAS  Google Scholar 

  27. Wakayama Y, Hirako S, Ogawa T, Jimi T, Shioda S (2014) Upregulated expression of AQP 7 in the skeletal muscles of obese ob/ob mice. Acta Histochem Cytochem 47:27–33

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lebeck J, Sondergaard E, Nielsen S (2018) Increased AQP7 abundance in skeletal muscle from obese men with type 2 diabetes. Am J Physiol Endocrinol Metab 315:E367–EE73

    Article  CAS  PubMed  Google Scholar 

  29. Fruhbeck G, Lopez M, Dieguez C (2007) Role of caveolins in body weight and insulin resistance regulation. Trends Endocrinol Metab 18:177–182

    Article  PubMed  Google Scholar 

  30. Parton RG, del Pozo MA (2013) Caveolae as plasma membrane sensors, protectors and organizers. Nat Rev Mol Cell Biol 14:98–112

    Article  CAS  PubMed  Google Scholar 

  31. Le Lay S, Krief S, Farnier C, Lefrere I, Le Liepvre X, Bazin R et al (2001) Cholesterol, a cell size-dependent signal that regulates glucose metabolism and gene expression in adipocytes. J Biol Chem 276:16904–16910

    Article  PubMed  Google Scholar 

  32. Cifuentes M, Albala C, Rojas CV (2008) Differences in lipogenesis and lipolysis in obese and non-obese adult human adipocytes. Biol Res 41:197–204

    Article  PubMed  Google Scholar 

Download references

Funding

Funding was provided by the University of Patras, School of Medicine, Patras, Greece.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Research Laboratory of the Division of Pediatric Endocrinology and Diabetes, University of Patras School of Medicine, Patras, Greece

    Roza Mourelatou, Eirini Kostopoulou & Bessie E. Spiliotis

  2. Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, Laboratory of Biochemistry, University of Peloponnese, Sparta, Lakonias, Greece

    Andrea Paola Rojas-Gil

  3. Department of Surgery, Morbid Obesity Unit, University Hospital of Patras, University of Patras School of Medicine, Patras, Greece

    Ioannis Kehagias & Fotis E. Kalfarentzos

  4. Fifth Surgical Clinic, Eugenideio Hospital, University of Athens School of Medicine, Athens, Greece

    Dimitris Linos

Authors
  1. Roza Mourelatou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eirini Kostopoulou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrea Paola Rojas-Gil
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ioannis Kehagias
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dimitris Linos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fotis E. Kalfarentzos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bessie E. Spiliotis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bessie E. Spiliotis.

Ethics declarations

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.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mourelatou, R., Kostopoulou, E., Rojas-Gil, A.P. et al. Decreased adipocyte glucose transporter 4 (GLUT4) and aquaglyceroporin-7 (AQP7) in adults with morbid obesity: possible early markers of metabolic dysfunction. Hormones 18, 297–306 (2019). https://doi.org/10.1007/s42000-019-00130-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42000-019-00130-8

Keywords

Search

Navigation