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Integrative Biology

Diet-induced weight loss decreases adipose tissue oxygen tension with parallel changes in adipose tissue phenotype and insulin sensitivity in overweight humans

International Journal of Obesity volume 41, pages 722–728 (2017)Cite this article

Subjects

Abstract

BACKGROUND/OBJECTIVES:

Although adipose tissue (AT) hypoxia is present in rodent models of obesity, evidence for this in humans is limited. Here, we investigated the effects of diet-induced weight loss (WL) on abdominal subcutaneous AT oxygen tension (pO2), AT blood flow (ATBF), AT capillary density, AT morphology and transcriptome, systemic inflammatory markers and insulin sensitivity in humans.

SUBJECTS/METHODS:

Fifteen overweight and obese individuals underwent a dietary intervention (DI), consisting of a 5-week very-low-calorie diet (VLCD, 500 kcal day−1; WL), and a subsequent 4-week weight stable diet (WS). Body composition, AT pO2 (optochemical monitoring), ATBF (133Xe washout), and whole-body insulin sensitivity were determined, and AT biopsies were collected at baseline, end of WL (week 5) and end of WS (week 9).

RESULTS:

Body weight, body fat percentage and adipocyte size decreased significantly during the DI period. The DI markedly decreased AT pO2 and improved insulin sensitivity, but did not alter ATBF. Finally, the DI increased AT gene expression of pathways related to mitochondrial biogenesis and non-mitochondrial oxygen consumption.

CONCLUSIONS:

VLCD-induced WL markedly decreases abdominal subcutaneous AT pO2, which is paralleled by a reduction in adipocyte size, increased AT gene expression of mitochondrial biogenesis markers and non-mitochondrial oxygen consumption pathways, and improved whole-body insulin sensitivity in humans.

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References

  1. Rosen ED, Spiegelman BM . What we talk about when we talk about fat. Cell 2014; 156: 20–44.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Kloting N, Bluher M . Adipocyte dysfunction, inflammation and metabolic syndrome. Rev Endocr Metab Disord 2014; 15: 277–287.

    Article  Google Scholar 

  4. Goossens GH, Blaak EE . Adipose tissue oxygen tension: implications for chronic metabolic and inflammatory diseases. Curr Opin Clin Nutr Metab Care 2012; 15: 539–546.

    Article  CAS  Google Scholar 

  5. Yin J, Gao Z, He Q, Zhou D, Guo Z, Ye J . Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue. Am J Physiol Endocrinol Metab 2009; 296: E333–E342.

    Article  CAS  Google Scholar 

  6. Trayhurn P . Hypoxia and adipose tissue function and dysfunction in obesity. Physiol Rev 2013; 93: 1–21.

    Article  CAS  Google Scholar 

  7. Blaak EE, van Baak MA, Kemerink GJ, Pakbiers MT, Heidendal GA, Saris WH . Beta-adrenergic stimulation and abdominal subcutaneous fat blood flow in lean, obese, and reduced-obese subjects. Metabolism 1995; 44: 183–187.

    Article  CAS  Google Scholar 

  8. Goossens GH, Jocken JW, Blaak EE, Schiffers PM, Saris WH, van Baak MA . Endocrine role of the renin-angiotensin system in human adipose tissue and muscle: effect of beta-adrenergic stimulation. Hypertension 2007; 49: 542–547.

    Article  CAS  Google Scholar 

  9. Trayhurn P, Wood IS . Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 2004; 92: 347–355.

    Article  CAS  Google Scholar 

  10. Ye J, Gao Z, Yin J, He Q . Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab 2007; 293: E1118–E1128.

    Article  CAS  Google Scholar 

  11. Rausch ME, Weisberg S, Vardhana P, Tortoriello DV . Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int J Obes (Lond) 2008; 32: 451–463.

    Article  CAS  Google Scholar 

  12. Hodson L, Humphreys SM, Karpe F, Frayn KN . Metabolic signatures of human adipose tissue hypoxia in obesity. Diabetes 2013; 62: 1417–1425.

    Article  CAS  Google Scholar 

  13. Pasarica M, Sereda OR, Redman LM, Albarado DC, Hymel DT, Roan LE et al. Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes 2009; 58: 718–725.

    Article  CAS  Google Scholar 

  14. Goossens GH, Bizzarri A, Venteclef N, Essers Y, Cleutjens JP, Konings E et al. Increased adipose tissue oxygen tension in obese compared with lean men is accompanied by insulin resistance, impaired adipose tissue capillarization, and inflammation. Circulation 2011; 124: 67–76.

    Article  CAS  Google Scholar 

  15. Yin X, Lanza IR, Swain JM, Sarr MG, Nair KS, Jensen MD . Adipocyte mitochondrial function is reduced in human obesity independent of fat cell size. J Clin Endocrinol Metab 2014; 99: E209–E216.

    Article  CAS  Google Scholar 

  16. Heinonen S, Buzkova J, Muniandy M, Kaksonen R, Ollikainen M, Ismail K et al. Impaired mitochondrial biogenesis in adipose tissue in acquired obesity. Diabetes 2015; 64: 3135–3145.

    Article  CAS  Google Scholar 

  17. Vink RG, Roumans NJ, Arkenbosch LA, Mariman EC, van Baak MA . The effect of rate of weight loss on long-term weight regain in adults with overweight and obesity. Obesity (Silver Spring) 2016; 24: 321–327.

    Article  CAS  Google Scholar 

  18. Cajlakovic MM, Bizzarri A, Goossens GH, Knez I, Suppan M, Ovcina I et al. Advances in Chemical Sensors: Optochemical Sensor Systems for In-vivo Continuous Monitoring of Blood Gases in Adipose Tissue in Vital Organs. InTech Publisher: Rijeka, Croatia, Advances in Chemical Sensors, 2012.

  19. Samra JS, Frayn KN, Giddings JA, Clark ML, Macdonald IA . Modification and validation of a commercially available portable detector for measurement of adipose tissue blood flow. Clin Physiol 1995; 15: 241–248.

    Article  CAS  Google Scholar 

  20. Timmers S, Konings E, Bilet L, Houtkooper RH, van de Weijer T, Goossens GH et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab 2011; 14: 612–622.

    Article  CAS  Google Scholar 

  21. Lin K, Kools H, de Groot PJ, Gavai AK, Basnet RK, Cheng F et al. MADMAX - Management and analysis database for multiple ~omics experiments. J Integr Bioinform 2011; 8: 160.

    Google Scholar 

  22. Hansen M, Lund MT, Gregers E, Kraunsoe R, Van Hall G, Helge JW et al. Adipose tissue mitochondrial respiration and lipolysis before and after a weight loss by diet and RYGB. Obesity (Silver Spring) 2015; 23: 2022–2029.

    Article  CAS  Google Scholar 

  23. Ganesan G, Warren RV, Leproux A, Compton M, Cutler K, Wittkopp S et al. Diffuse optical spectroscopic imaging of subcutaneous adipose tissue metabolic changes during weight loss. Int J Obes (Lond) 2016; 40: 1292–1300.

    Article  CAS  Google Scholar 

  24. Lecoultre V, Peterson CM, Covington JD, Ebenezer PJ, Frost EA, Schwarz JM et al. Ten nights of moderate hypoxia improves insulin sensitivity in obese humans. Diabetes Care 2013; 36: e197–e198.

    Article  Google Scholar 

  25. Goossens GH, Blaak EE . Adipose tissue dysfunction and impaired metabolic health in human obesity: a matter of oxygen? Front Endocrinol 2015; 6: 55.

    Article  Google Scholar 

  26. Xue Y, Petrovic N, Cao R, Larsson O, Lim S, Chen S et al. Hypoxia-independent angiogenesis in adipose tissues during cold acclimation. Cell Metab 2009; 9: 99–109.

    Article  CAS  Google Scholar 

  27. Hausman GJ, Richardson RL . Adipose tissue angiogenesis. J Animal Sci 2004; 82: 925–934.

    Article  CAS  Google Scholar 

  28. Fischer B, Schottl T, Schempp C, Fromme T, Hauner H, Klingenspor M et al. Inverse relationship between body mass index and mitochondrial oxidative phosphorylation capacity in human subcutaneous adipocytes. Am J Physiol Endocrinol Metab 2015; 309: E380–E387.

    Article  CAS  Google Scholar 

  29. Duivenvoorde LP, van Schothorst EM, Bunschoten A, Keijer J . Dietary restriction of mice on a high-fat diet induces substrate efficiency and improves metabolic health. J Mol Endocrinol 2011; 47: 81–97.

    Article  CAS  Google Scholar 

  30. Civitarese AE, Carling S, Heilbronn LK, Hulver MH, Ukropcova B, Deutsch WA et al. Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med 2007; 4: e76.

    Article  Google Scholar 

  31. Nisoli E, Tonello C, Cardile A, Cozzi V, Bracale R, Tedesco L et al. Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 2005; 310: 314–317.

    Article  CAS  Google Scholar 

  32. Ozer A, Bruick RK . Non-heme dioxygenases: cellular sensors and regulators jelly rolled into one? Nat Chem Biol 2007; 3: 144–153.

    Article  CAS  Google Scholar 

  33. McDonough MA, Loenarz C, Chowdhury R, Clifton IJ, Schofield CJ . Structural studies on human 2-oxoglutarate dependent oxygenases. Curr Opin Struct Biol 2010; 20: 659–672.

    Article  CAS  Google Scholar 

  34. Ames BN, Shigenaga MK, Hagen TM . Mitochondrial decay in aging. Biochim Biophys Acta 1995; 1271: 165–170.

    Article  Google Scholar 

  35. Rolfe DF, Brown GC . Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev 1997; 77: 731–758.

    Article  CAS  Google Scholar 

  36. Kosteli A, Sugaru E, Haemmerle G, Martin JF, Lei J, Zechner R et al. Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue. J Clin Invest 2010; 120: 3466–3479.

    Article  CAS  Google Scholar 

  37. Capel F, Klimcakova E, Viguerie N, Roussel B, Vitkova M, Kovacikova M et al. Macrophages and adipocytes in human obesity: adipose tissue gene expression and insulin sensitivity during calorie restriction and weight stabilization. Diabetes 2009; 58: 1558–1567.

    Article  CAS  Google Scholar 

  38. Johansson LE, Danielsson AP, Parikh H, Klintenberg M, Norstrom F, Groop L et al. Differential gene expression in adipose tissue from obese human subjects during weight loss and weight maintenance. Am J Clin Nutr 2012; 96: 196–207.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Laura Arkenbosch (Department of Human Biology, Maastricht University Medical Centre+, Maastricht, The Netherlands) for excellent dietary guidance, and Judith Sluimer (Department of Pathology, Maastricht University Medical Centre+, Maastricht, The Netherlands) and Michael Suppan (Joanneum Research Forschungsgesellschaft mbH, Weiz, Austria) for technical support. We thank the participants for their contribution to the study. This study was funded by the European Foundation for the Study of Diabetes (EFSD; Clinical Research Grant (to GHG)) and The Netherlands Organization for Scientific Research (NWO; TOP 200500001 to MAvB and ECM). Trial registration: www.clinicaltrials.gov (NCT01559415).

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Authors and Affiliations

  1. Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands

    R G Vink, N J Roumans, M A A Vogel, E E Blaak, E C Mariman, M A van Baak & G H Goossens

  2. Joanneum Research Forschungsgesellschaft mbH, MATERIALS - Institute for Surface Technologies and Photonic, Sensorsystems, Weiz, Austria

    M Čajlaković

  3. Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre+, Maastricht, The Netherlands

    J P M Cleutjens

  4. Division of Human Nutrition, Nutrition, Metabolism and Genomics Group, Wageningen University, Wageningen, The Netherlands

    M V Boekschoten & P Fazelzadeh

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  1. R G Vink
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Correspondence to G H Goossens.

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Vink, R., Roumans, N., Čajlaković, M. et al. Diet-induced weight loss decreases adipose tissue oxygen tension with parallel changes in adipose tissue phenotype and insulin sensitivity in overweight humans. Int J Obes 41, 722–728 (2017). https://doi.org/10.1038/ijo.2017.38

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