Skip to main content
SpringerLink
Log in

Dietary fat may modulate adipose tissue homeostasis through the processes of autophagy and apoptosis

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

Obesity increases the risk of cardiovascular disease, type 2 diabetes mellitus and cancer development. Autophagy and apoptosis are critical processes for development and homeostasis in multicellular organisms and have been linked to a variety of disorders. We aimed to investigate whether the quantity and quality of dietary fat can influence these processes in the adipose tissue of obese people.

Methods

A randomized, controlled trial within the LIPGENE study assigned 39 obese people with metabolic syndrome to 1 of 4 diets: (a) a high-saturated fatty acid diet, (b) a high-monounsaturated fatty acid (HMUFA) diet, and (c, d) two low-fat, high-complex carbohydrate diets supplemented with long-chain n-3 polyunsaturated fatty acids (LFHCC n-3) or placebo (LFHCC), for 12 weeks each.

Results

We found an increase in the expression of autophagy-related BECN1 and ATG7 genes after the long-term consumption of the HMUFA diet (p = 0.001 and p = 0.004, respectively) and an increase in the expression of the apoptosis-related CASP3 gene after the long-term consumption of the LFHCC and LFHCC n-3 diets (p = 0.001 and p = 0.029, respectively). CASP3 and CASP7 gene expression changes correlated with HOMA index.

Conclusion

Our results suggest that the processes of autophagy and apoptosis in adipose tissue may be modified by diet and that the consumption of a diet rich in monounsaturated fat may contribute to adipose tissue homeostasis by increasing autophagy. They also reinforce the notion that apoptosis in adipose tissue is linked to insulin resistance.

Clinical Trial Registration Number

ClinicalTrials.gov NCT00429195.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. James WP (2008) WHO recognition of the global obesity epidemic. Int J Obes 32(Suppl 7):S120–S126

    Article  Google Scholar 

  2. Haslam DW, James WP (2005) Obes Lancet 366:1197–1209

    Article  Google Scholar 

  3. Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C (2004) Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Arterioscler Thromb Vasc Biol 24:e13–e18

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  5. Suganami T, Tanaka M, Ogawa Y (2012) Adipose tissue inflammation and ectopic lipid accumulation. Endocr J 59:849–857

    Article  CAS  Google Scholar 

  6. Tinahones FJ, Coin Araguez L, Murri M, Oliva Olivera W, Mayas Torres MD, Barbarroja N, Gomez Huelgas R, Malagon MM, El Bekay R (2012) Caspase induction and BCL2 inhibition in human adipose tissue: a potential relationship with insulin signaling alteration. Diabetes Care 36:513–521

    Article  Google Scholar 

  7. Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 116:205–219

    Article  CAS  Google Scholar 

  8. Finkel T, Serrano M, Blasco MA (2007) The common biology of cancer and ageing. Nature 448:767–774

    Article  CAS  Google Scholar 

  9. Dong C, Zheng H, Huang S, You N, Xu J, Ye X, Zhu Q, Feng Y, You Q, Miao H, Ding D, Lu Y (2015) Heme oxygenase-1 enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis. Exp Cell Res 337:146–159

    Article  CAS  Google Scholar 

  10. Mitani T, Minami M, Harada N, Ashida H, Yamaji R (2015) Autophagic degradation of the androgen receptor mediated by increased phosphorylation of p62 suppresses apoptosis in hypoxia. Cell Signal 27:1994–2001

    Article  CAS  Google Scholar 

  11. Savill J, Fadok V (2000) Corpse clearance defines the meaning of cell death. Nature 407:784–788

    Article  CAS  Google Scholar 

  12. Jung HS, Chung KW, Won Kim J, Kim J, Komatsu M, Tanaka K, Nguyen YH, Kang TM, Yoon KH, Kim JW, Jeong YT, Han MS, Lee MK, Kim KW, Shin J, Lee MS (2008) Loss of autophagy diminishes pancreatic beta cell mass and function with resultant hyperglycemia. Cell Metab 8:318–324

    Article  CAS  Google Scholar 

  13. Ebato C, Uchida T, Arakawa M, Komatsu M, Ueno T, Komiya K, Azuma K, Hirose T, Tanaka K, Kominami E, Kawamori R, Fujitani Y, Watada H (2008) Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet. Cell Metab 8:325–332

    Article  CAS  Google Scholar 

  14. Yang L, Li P, Fu S, Calay ES, Hotamisligil GS (2010) Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance. Cell Metab 11:467–478

    Article  CAS  Google Scholar 

  15. Keuper M, Bluher M, Schon MR, Moller P, Dzyakanchuk A, Amrein K, Debatin KM, Wabitsch M, Fischer-Posovszky P (2011) An inflammatory micro-environment promotes human adipocyte apoptosis. Mol Cell Endocrinol 339:105–113

    Article  CAS  Google Scholar 

  16. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Wang S, Fortier M, Greenberg AS, Obin MS (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46:2347–2355

    Article  CAS  Google Scholar 

  17. Young MM, Takahashi Y, Khan O, Park S, Hori T, Yun J, Sharma AK, Amin S, Hu CD, Zhang J, Kester M, Wang HG (2012) Autophagosomal membrane serves as platform for intracellular death-inducing signaling complex (iDISC)-mediated caspase-8 activation and apoptosis. J Biol Chem 287:12455–12468

    Article  CAS  Google Scholar 

  18. Riserus U, Willett WC, Hu FB (2009) Dietary fats and prevention of type 2 diabetes. Prog Lipid Res 48:44–51

    Article  CAS  Google Scholar 

  19. Buttar HS, Li T, Ravi N (2005) Prevention of cardiovascular diseases: role of exercise, dietary interventions, obesity and smoking cessation. Exp Clin Cardiol 10:229–249

    CAS  Google Scholar 

  20. Camargo A, Meneses ME, Rangel-Zuniga OA, Perez-Martinez P, Marin C, Delgado-Lista J, Paniagua JA, Tinahones FJ, Roche H, Malagon MM, Perez-Jimenez F, Lopez-Miranda J (2013) Endoplasmic reticulum stress in adipose tissue determines postprandial lipoprotein metabolism in metabolic syndrome patients. Mol Nutr Food Res 57:2166–2176

    Article  CAS  Google Scholar 

  21. Meneses ME, Camargo A, Perez-Martinez P, Delgado-Lista J, Cruz-Teno C, Jimenez-Gomez Y, Paniagua JA, Gutierrez-Mariscal FM, Tinahones FJ, Vidal-Puig A, Roche HM, Perez-Jimenez F, Malagon MM, Lopez-Miranda J (2011) Postprandial inflammatory response in adipose tissue of patients with metabolic syndrome after the intake of different dietary models. Mol Nutr Food Res 55:1759–1770

    Article  CAS  Google Scholar 

  22. Pena-Orihuela P, Camargo A, Rangel-Zuniga OA, Perez-Martinez P, Cruz-Teno C, Delgado-Lista J, Yubero-Serrano EM, Paniagua JA, Tinahones FJ, Malagon MM, Roche HM, Perez-Jimenez F, Lopez-Miranda J (2013) Antioxidant system response is modified by dietary fat in adipose tissue of metabolic syndrome patients. J Nutr Biochem 24:1717–1723

    Article  CAS  Google Scholar 

  23. Levonen AL, Hill BG, Kansanen E, Zhang J, Darley-Usmar VM (2014) Redox regulation of antioxidants, autophagy, and the response to stress: implications for electrophile therapeutics. Free Radic Biol Med 71:196–207

    Article  CAS  Google Scholar 

  24. Shaw DI, Tierney AC, McCarthy S, Upritchard J, Vermunt S, Gulseth HL, Drevon CA, Blaak EE, Saris WH, Karlstrom B, Helal O, Defoort C, Gallego R, Lopez-Miranda J, Siedlecka D, Malczewska-Malec M, Roche HM, Lovegrove JA (2009) LIPGENE food-exchange model for alteration of dietary fat quantity and quality in free-living participants from eight European countries. Br J Nutr 101:750–759

    Article  CAS  Google Scholar 

  25. Camargo A, Meneses ME, Perez-Martinez P, Delgado-Lista J, Jimenez-Gomez Y, Cruz-Teno C, Tinahones FJ, Paniagua JA, Perez-Jimenez F, Roche HM, Malagon MM, Lopez-Miranda J (2014) Dietary fat differentially influences the lipids storage on the adipose tissue in metabolic syndrome patients. Eur J Nutr 53:617–626

    Article  CAS  Google Scholar 

  26. Hotamisligil GS (2007) Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140:900–917

    Article  Google Scholar 

  27. Ogata M, Hino S, Saito A, Morikawa K, Kondo S, Kanemoto S, Murakami T, Taniguchi M, Tanii I, Yoshinaga K, Shiosaka S, Hammarback JA, Urano F, Imaizumi K (2006) Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol 26:9220–9231

    Article  CAS  Google Scholar 

  28. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402:672–676

    Article  CAS  Google Scholar 

  29. Pattingre S, Espert L, Biard-Piechaczyk M, Codogno P (2008) Regulation of macroautophagy by mTOR and Beclin 1 complexes. Biochimie 90:313–323

    Article  CAS  Google Scholar 

  30. Ryter SW, Choi AM (2013) Regulation of autophagy in oxygen-dependent cellular stress. Curr Pharm Des 19:2747–2756

    Article  CAS  Google Scholar 

  31. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114:1752–1761

    Article  CAS  Google Scholar 

  32. Fulda S, Gorman AM, Hori O, Samali A (2010) Cellular stress responses: cell survival and cell death. Int J Cell Biol 2010:214074

    Google Scholar 

  33. Wang L, Yu C, Lu Y, He P, Guo J, Zhang C, Song Q, Ma D, Shi T, Chen Y (2007) TMEM166, a novel transmembrane protein, regulates cell autophagy and apoptosis. Apoptosis 12:1489–1502

    Article  CAS  Google Scholar 

  34. Benbrook DM, Long A (2012) Integration of autophagy, proteasomal degradation, unfolded protein response and apoptosis. Exp Oncol 34:286–297

    CAS  Google Scholar 

Download references

Acknowledgments

The CIBEROBN is an initiative of the Instituto de Salud Carlos III, Madrid, Spain. This work was supported in part by Research Grants from the European Union (LIPGENE European Integrated Project-505944), from the Ministerio de Ciencia e Innovacion [Grant Numbers AGL2004-07907, AGL2006-01979, AGL2009-2270 (to J.L.-M.)]; Ministerio de Economia y Competitividad [AGL2012/39615, PIE14/00005, PIE 14/00031 (to J L-M)]; CIBER Fisiopatologia de la Obesidad y Nutricion [Grant Number CB06/03/0047]; Consejeria de Innovacion, Ciencia y Empresa, Junta de Andalucia [Grant Number P06- CTS-01425 and CVI-7450 (to J.L.-M.); and Consejeria de Salud, Junta de Andalucia [Grant Numbers 06/128, 07/43, PI-0193 (to J.L.-M.)].); Fondo Europeo de Desarrollo Regional (FEDER). Antonio Camargo is supported by an Instituto de Salud Carlos III research contract (Programa Miguel-Servet CP14/00114). Author contributions: AC, P P-M, HM R, and JL-M designed research; AC, OAR-Z, J A-D, J D-L, F G-D, S G-C, CM, YA, EM Y-S, and J L-M conducted research; AC, OAR-Z, J D-L, FJ T, and P P-M analyzed data or performed statistical analysis; AC wrote paper; AC, P P-M, HM R, and JL-M had primary responsibility for final content.

Author information

Authors and Affiliations

  1. Lipids and Atherosclerosis Unit, IMIBIC, Reina Sofia University Hospital, University of Cordoba, Av. Menendez Pidal, s/n, 14004, Córdoba, Spain

    A. Camargo, O. A. Rangel-Zúñiga, J. Alcalá-Díaz, F. Gomez-Delgado, J. Delgado-Lista, S. García-Carpintero, C. Marín, Y. Almadén, E. M. Yubero-Serrano, J. López-Moreno, P. Pérez-Martínez & J. López-Miranda

  2. CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Córdoba, Spain

    A. Camargo, O. A. Rangel-Zúñiga, J. Alcalá-Díaz, F. Gomez-Delgado, J. Delgado-Lista, S. García-Carpintero, C. Marín, Y. Almadén, E. M. Yubero-Serrano, J. López-Moreno, F. J. Tinahones, P. Pérez-Martínez & J. López-Miranda

  3. Endocrinology and Nutrition Service, Hospital Virgen de la Victoria, Malaga, Spain

    F. J. Tinahones

  4. UCD Institute of Food and Health, UCD Conway Institute, School of Public Health and Population Sciences, University College Dublin, Dublin, UK

    H. M. Roche

Authors
  1. A. Camargo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. A. Rangel-Zúñiga
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Alcalá-Díaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. Gomez-Delgado
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Delgado-Lista
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. García-Carpintero
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C. Marín
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Y. Almadén
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E. M. Yubero-Serrano
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J. López-Moreno
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. F. J. Tinahones
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. P. Pérez-Martínez
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. H. M. Roche
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. J. López-Miranda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. López-Miranda.

Ethics declarations

Conflict of interest

None of the authors has any conflict of interests that could affect the performance of the work or the interpretation of the data.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 13 kb)

Supplementary material 2 (DOCX 13 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Camargo, A., Rangel-Zúñiga, O.A., Alcalá-Díaz, J. et al. Dietary fat may modulate adipose tissue homeostasis through the processes of autophagy and apoptosis. Eur J Nutr 56, 1621–1628 (2017). https://doi.org/10.1007/s00394-016-1208-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-016-1208-y

Keywords

Search

Navigation