Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Integrative Biology

Adipose tissue gene expression is differentially regulated with different rates of weight loss in overweight and obese humans

International Journal of Obesity volume 41, pages 309–316 (2017)Cite this article

Subjects

Abstract

Background/Objectives:

Moderate weight loss (WL) can ameliorate adverse health effects associated with obesity, reflected by an improved adipose tissue (AT) gene expression profile. However, the effect of rate of WL on the AT transcriptome is unknown. We investigated the global AT gene expression profile before and after two different rates of WL that resulted in similar total WL, and after a subsequent weight stabilization period.

Subjects/Methods:

In this randomized controlled trial, 25 male and 28 female individuals (body mass index (BMI): 28–35 kg m−2) followed either a low-calorie diet (LCD; 1250 kcal day−1) for 12 weeks or a very-low-calorie diet (VLCD; 500 kcal day−1) for 5 weeks (WL period) and a subsequent weight stable (WS) period of 4 weeks. The WL period and WS period together is termed dietary intervention (DI) period. Abdominal subcutaneous AT biopsies were collected for microarray analysis and gene expression changes were calculated for all three periods in the LCD group, VLCD group and between diets (ΔVLCD−ΔLCD).

Results:

WL was similar between groups during the WL period (LCD: −8.1±0.5 kg, VLCD: −8.9±0.4 kg, difference P=0.25). Overall, more genes were significantly regulated and changes in gene expression appeared more pronounced in the VLCD group compared with the LCD group. Gene sets related to mitochondrial function, adipogenesis and immunity/inflammation were more strongly upregulated on a VLCD compared with a LCD during the DI period (positive ΔVLCD−ΔLCD). Neuronal and olfactory-related gene sets were decreased during the WL period and DI period in the VLCD group.

Conclusions:

The rate of WL (LCD vs VLCD), with similar total WL, strongly regulates AT gene expression. Increased mitochondrial function, angiogenesis and adipogenesis on a VLCD compared with a LCD reflect potential beneficial diet-induced changes in AT, whereas differential neuronal and olfactory regulation suggest functions of these genes beyond the current paradigm.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

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. Hajer GR, van Haeften TW, Visseren FL . Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J 2008; 29: 2959–2971.

    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. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001; 344: 1343–1350.

    Article  CAS  Google Scholar 

  5. Brown T, Avenell A, Edmunds LD, Moore H, Whittaker V, Avery L et al. Systematic review of long-term lifestyle interventions to prevent weight gain and morbidity in adults. Obes Rev 2009; 10: 627–638.

    Article  CAS  Google Scholar 

  6. 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 

  7. 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 

  8. 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 

  9. 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 

  10. Jahansouz C, Serrot FJ, Frohnert BI, Foncea RE, Dorman RB, Slusarek B et al. Roux-en-Y gastric bypass acutely decreases protein carbonylation and increases expression of mitochondrial biogenesis genes in subcutaneous adipose tissue. Obes Surg 2015; 25: 2376–2385.

    Article  Google Scholar 

  11. You T, Nicklas BJ . Chronic inflammation: role of adipose tissue and modulation by weight loss. Curr Diabetes Rev 2006; 2: 29–37.

    Article  Google Scholar 

  12. Capel F, Viguerie N, Vega N, Dejean S, Arner P, Klimcakova E et al. Contribution of energy restriction and macronutrient composition to changes in adipose tissue gene expression during dietary weight-loss programs in obese women. J Clin Endocrinol Metab 2008; 93: 4315–4322.

    Article  CAS  Google Scholar 

  13. 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 2016; 24: 321–327.

    Article  CAS  Google Scholar 

  14. Smyth GK . Limma: linear models for microarray data. In: Gentleman R et al. (eds). Bioinformatics and Computational Biology Solutions Using R and Bioconductor. Springer: New York, NY, USA, 2005, pp 397–420.

    Chapter  Google Scholar 

  15. Benjamini Y, Hochberg Y . Controlling the false discovery rate—a practical and powerful approach to multiple testing. J R Stat Soc B Met 1995; 57: 289–300.

    Google Scholar 

  16. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 2005; 102: 15545–15550.

    Article  CAS  Google Scholar 

  17. Smilde AK, Jansen JJ, Hoefsloot HC, Lamers RJ, van der Greef J, Timmerman ME . ANOVA-simultaneous component analysis (ASCA): a new tool for analyzing designed metabolomics data. Bioinformatics 2005; 21: 3043–3048.

    Article  CAS  Google Scholar 

  18. Vis DJ, Westerhuis JA, Smilde AK, van der Greef J . Statistical validation of megavariate effects in ASCA. BMC Bioinformatics 2007; 8: 322.

    Article  Google Scholar 

  19. 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 

  20. Hotamisligil GS . Inflammation and metabolic disorders. Nature 2006; 444: 860–867.

    Article  CAS  Google Scholar 

  21. Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C et al. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 2005; 54: 2277–2286.

    Article  CAS  Google Scholar 

  22. 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 

  23. Rossmeislova L, Malisova L, Kracmerova J, Tencerova M, Kovacova Z, Koc M et al. Weight loss improves the adipogenic capacity of human preadipocytes and modulates their secretory profile. Diabetes 2013; 62: 1990–1995.

    Article  CAS  Google Scholar 

  24. Cristancho AG, Lazar MA . Forming functional fat: a growing understanding of adipocyte differentiation. Nature Rev Mol Cell Biol 2011; 12: 722–734.

    Article  CAS  Google Scholar 

  25. Bartness TJ, Liu Y, Shrestha YB, Ryu V . Neural innervation of white adipose tissue and the control of lipolysis. Front Neuroendocrinol 2014; 35: 473–493.

    Article  CAS  Google Scholar 

  26. Patel JN, Coppack SW, Goldstein DS, Miles JM, Eisenhofer G . Norepinephrine spillover from human adipose tissue before and after a 72- hour fast. J Clin Endocrinol Metab 2002; 87: 3373–3377.

    Article  CAS  Google Scholar 

  27. Cleland TA . Construction of odor representations by olfactory bulb microcircuits. Prog Brain Res 2014; 208: 177–203.

    Article  Google Scholar 

  28. Palouzier-Paulignan B, Lacroix MC, Aime P, Baly C, Caillol M, Congar P et al. Olfaction under metabolic influences. Chem Senses 2012; 37: 769–797.

    Article  CAS  Google Scholar 

  29. Stafford LD, Whittle A . Obese individuals have higher preference and sensitivity to odor of chocolate. Chem Senses 2015; 40: 279–284.

    Article  CAS  Google Scholar 

  30. van Helden YG, Godschalk RW, Heil SG, Bunschoten A, Hessel S, Amengual J et al. Downregulation of Fzd6 and Cthrc1 and upregulation of olfactory receptors and protocadherins by dietary beta-carotene in lungs of Bcmo1-/- mice. Carcinogenesis 2010; 31: 1329–1337.

    Article  CAS  Google Scholar 

  31. Primeaux SD, Braymer HD, Bray GA . High fat diet differentially regulates the expression of olfactory receptors in the duodenum of obesity-prone and obesity-resistant rats. Dig Dis Sci 2013; 58: 72–76.

    Article  CAS  Google Scholar 

  32. Mariman EC, Szklarczyk R, Bouwman FG, Aller EE, van Baak MA, Wang P . Olfactory receptor genes cooperate with protocadherin genes in human extreme obesity. Genes Nutr 2015; 10: 465.

    Article  Google Scholar 

  33. Henegar C, Tordjman J, Achard V, Lacasa D, Cremer I, Guerre-Millo M et al. Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity. Genome Biol 2008; 9: R14.

    Article  Google Scholar 

  34. Kolehmainen M, Salopuro T, Schwab US, Kekalainen J, Kallio P, Laaksonen DE et al. Weight reduction modulates expression of genes involved in extracellular matrix and cell death: the GENOBIN study. Int J Obes 2008; 32: 292–303.

    Article  CAS  Google Scholar 

  35. Divoux A, Tordjman J, Lacasa D, Veyrie N, Hugol D, Aissat A et al. Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss. Diabetes 2010; 59: 2817–2825.

    Article  CAS  Google Scholar 

  36. Mariman EC, Wang P . Adipocyte extracellular matrix composition, dynamics and role in obesity. Cell Mol Life Sci 2010; 67: 1277–1292.

    Article  CAS  Google Scholar 

  37. Divoux A, Clement K . Architecture and the extracellular matrix: the still unappreciated components of the adipose tissue. Obes Rev 2011; 12: e494–e503.

    Article  CAS  Google Scholar 

  38. Gaj S, Eijssen L, Mensink RP, Evelo CT . Validating nutrient-related gene expression changes from microarrays using RT(2) PCR-arrays. Genes Nutr 2008; 3: 153–157.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the study participants for their contribution to the trial. We also like to thank Martina Kutmon and Michiel Adriaens from Maastricht Centre for Systems Biology (MaCSBio) for their suggestions and assistance. This project/research has been made possible with support of the Dutch Province of Limburg. This study was supported by the Netherlands Organisation for Scientific Research TOP, Grant Number: 200500001.

Author information

Author notes

  1. R G Vink and N J Roumans: These authors contributed equally to this work.

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 van Baak & E C Mariman

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

    P Fazelzadeh & M V Boekschoten

  3. Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands

    S H K Tareen

Authors
  1. R G Vink
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N J Roumans
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P Fazelzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S H K Tareen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M V Boekschoten
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M A van Baak
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E C Mariman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R G Vink.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on International Journal of Obesity website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vink, R., Roumans, N., Fazelzadeh, P. et al. Adipose tissue gene expression is differentially regulated with different rates of weight loss in overweight and obese humans. Int J Obes 41, 309–316 (2017). https://doi.org/10.1038/ijo.2016.201

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2016.201

This article is cited by

Search

Advanced search

Quick links