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.

  • Review Article
  • Published:

Mechanisms of weight regain after weight loss — the role of adipose tissue

Nature Reviews Endocrinology volume 15, pages 274–287 (2019)Cite this article

Subjects

Abstract

One of the biggest challenges in the management of obesity is the prevention of weight regain after successful weight loss. Weight regain after weight loss has large interindividual variation. Although many factors probably contribute to this variation, we hypothesize that variability in biological responses associated with weight loss-induced shrinking of subcutaneous adipocytes has an important role. In this Review, we show that weight loss-induced variations in cellular stress, extracellular matrix remodelling, inflammatory responses, adipokine secretion and lipolysis seem to be associated with the amount of weight that is regained after successful weight loss. Weight regain could therefore, at least in part, depend on a combination of these factors. Further research on the causality of these associations could aid the development of effective strategies to prevent weight regain after successful weight loss.

Key points

  • Weight regain after successful weight loss is a major problem for many individuals, and many factors are probably involved in driving weight regain.

  • Loss of fat mass induces shrinkage of adipocytes, which is accompanied by cell stress, inflammation, altered adipokine secretion and reduced lipolysis.

  • In the absence of extracellular matrix remodelling during adipocyte shrinkage, mechanical stress builds up between the cell and the oversized extracellular matrix, which inhibits lipolysis and the release of fatty acids from adipocytes.

  • Weight loss induces an inflammatory response in adipose tissue.

  • Evidence for the involvement of epigenetic modifications, in particular microRNAs, in weight regain is sparse.

  • Knowledge of weight regain after weight loss is mainly based on associations, and so research into the causality of such associated factors is needed.

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

Fig. 1: Potential adipose tissue-related mechanisms involved in weight regain after weight loss.
Fig. 2: Adipocyte diameter distribution in different phases of weight loss and weight regain.
Fig. 3: Model of resolution of weight loss-induced adipocyte stress.
Fig. 4: Structure of the focal adhesion as the centre for mechanical stress.
Fig. 5: Working model for the role of weight loss-induced changes in adipose tissue in weight regain.

Similar content being viewed by others

References

  1. NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet 387, 1377–1396 (2016).

    Article  Google Scholar 

  2. Santos, I., Sniehotta, F. F., Marques, M. M., Carraca, E. V. & Teixeira, P. J. Prevalence of personal weight control attempts in adults: a systematic review and meta-analysis. Obes. Rev. 18, 32–50 (2017).

    Article  CAS  PubMed  Google Scholar 

  3. Anderson, J. W., Konz, E. C., Frederich, R. C. & Wood, C. L. Long-term weight-loss maintenance: a meta-analysis of US studies. Am. J. Clin. Nutr. 74, 579–584 (2001).

    Article  CAS  PubMed  Google Scholar 

  4. Look AHEAD Research Group. Eight-year weight losses with an intensive lifestyle intervention: the look AHEAD study. Obesity (Silver Spring) 22, 5–13 (2014).

    Article  Google Scholar 

  5. Christou, N. V., Look, D. & Maclean, L. D. Weight gain after short- and long-limb gastric bypass in patients followed for longer than 10 years. Ann. Surg. 244, 734–740 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Magro, D. O. et al. Long-term weight regain after gastric bypass: a 5-year prospective study. Obes. Surg. 18, 648–651 (2008).

    Article  PubMed  Google Scholar 

  7. Odom, J. et al. Behavioral predictors of weight regain after bariatric surgery. Obes. Surg. 20, 349–356 (2010).

    Article  PubMed  Google Scholar 

  8. Schwartz, M. W. et al. Obesity pathogenesis: an Endocrine Society scientific statement. Endocr. Rev. 38, 267–296 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Hopkins, M. & Blundell, J. E. Energy balance, body composition, sedentariness and appetite regulation: pathways to obesity. Clin. Sci. 130, 1615–1628 (2016).

    Article  CAS  Google Scholar 

  10. MacLean, P. S., Blundell, J. E., Mennella, J. A. & Batterham, R. L. Biological control of appetite: a daunting complexity. Obesity (Silver Spring) 25 (Suppl. 1), S8–S16 (2017).

    Article  Google Scholar 

  11. Dulloo, A. G., Jacquet, J., Miles-Chan, J. L. & Schutz, Y. Passive and active roles of fat-free mass in the control of energy intake and body composition regulation. Eur. J. Clin. Nutr. 71, 353–357 (2017).

    Article  CAS  PubMed  Google Scholar 

  12. Melby, C. L., Paris, H. L., Foright, R. M. & Peth, J. Attenuating the biologic drive for weight regain following weight loss: must what goes down always go back up? Nutrients 9, 468 (2017).

    Article  PubMed Central  CAS  Google Scholar 

  13. Ochner, C. N., Barrios, D. M., Lee, C. D. & Pi-Sunyer, F. X. Biological mechanisms that promote weight regain following weight loss in obese humans. Physiol. Behav. 120, 106–113 (2013).

    Article  CAS  PubMed  Google Scholar 

  14. Sumithran, P. & Proietto, J. The defence of body weight: a physiological basis for weight regain after weight loss. Clin. Sci. 124, 231–241 (2013).

    Article  Google Scholar 

  15. Mariman, E. C. Human biology of weight maintenance after weight loss. J. Nutrigenet. Nutrigenomics 5, 13–25 (2012).

    Article  PubMed  Google Scholar 

  16. Sumithran, P. et al. Long-term persistence of hormonal adaptations to weight loss. N. Engl. J. Med. 365, 1597–1604 (2011).

    Article  CAS  PubMed  Google Scholar 

  17. Munzberg, H., Laque, A., Yu, S., Rezai-Zadeh, K. & Berthoud, H. R. Appetite and body weight regulation after bariatric surgery. Obes. Rev. 16 (Suppl. 1), 77–90 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Lean, M. E. & Malkova, D. Altered gut and adipose tissue hormones in overweight and obese individuals: cause or consequence? Int. J. Obes. (Lond.) 40, 622–632 (2016).

    Article  CAS  Google Scholar 

  19. Verhoef, S. P., Camps, S. G., Bouwman, F. G., Mariman, E. C. & Westerterp, K. R. Physiological response of adipocytes to weight loss and maintenance. PLOS ONE 8, e58011 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Haczeyni, F., Bell-Anderson, K. S. & Farrell, G. C. Causes and mechanisms of adipocyte enlargement and adipose expansion. Obes. Rev. 19, 406–420 (2018).

    Article  CAS  PubMed  Google Scholar 

  21. Park, K. W., Halperin, D. S. & Tontonoz, P. Before they were fat: adipocyte progenitors. Cell Metab. 8, 454–457 (2008).

    Article  CAS  PubMed  Google Scholar 

  22. Engin, A. Fat cell and fatty acid turnover in obesity. Adv. Exp. Med. Biol. 960, 135–160 (2017).

    Article  CAS  PubMed  Google Scholar 

  23. Spalding, K. L. et al. Dynamics of fat cell turnover in humans. Nature 453, 783–787 (2008).

    Article  CAS  PubMed  Google Scholar 

  24. Tchoukalova, Y. D. et al. Regional differences in cellular mechanisms of adipose tissue gain with overfeeding. Proc. Natl Acad. Sci. USA 107, 18226–18231 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Arner, E. et al. Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes 59, 105–109 (2010).

    Article  CAS  PubMed  Google Scholar 

  26. Jonker, J. W. et al. A PPARgamma-FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis. Nature 485, 391–394 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Arner, P., Andersson, D. P., Backdahl, J., Dahlman, I. & Ryden, M. Weight gain and impaired glucose metabolism in women are predicted by inefficient subcutaneous fat cell lipolysis. Cell Metab. 28, 45–54 (2018).

    Article  CAS  PubMed  Google Scholar 

  28. Khan, T. et al. Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol. Cell. Biol. 29, 1575–1591 (2009).

    Article  CAS  PubMed  Google Scholar 

  29. Henegar, C. et al. Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity. Genome Biol. 9, R14 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Muir, L. A. et al. Adipose tissue fibrosis, hypertrophy, and hyperplasia: correlations with diabetes in human obesity. Obesity (Silver Spring) 24, 597–605 (2016).

    Article  CAS  Google Scholar 

  31. Divoux, A. et al. Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss. Diabetes 59, 2817–2825 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Trayhurn, P. Hypoxia and adipocyte physiology: implications for adipose tissue dysfunction in obesity. Annu. Rev. Nutr. 34, 207–236 (2014).

    Article  CAS  PubMed  Google Scholar 

  33. Sun, K., Tordjman, J., Clement, K. & Scherer, P. E. Fibrosis and adipose tissue dysfunction. Cell Metab. 18, 470–477 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lin, N. & Simon, M. C. Hypoxia-inducible factors: key regulators of myeloid cells during inflammation. J. Clin. Invest. 126, 3661–3671 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Lin, Q. & Yun, Z. The hypoxia-inducible factor pathway in adipocytes: the role of HIF-2 in adipose inflammation and hypertrophic cardiomyopathy. Front. Endocrinol. (Lausanne) 6, 39 (2015).

    Google Scholar 

  36. Pasarica, M. et al. Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes 58, 718–725 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Goossens, G. H. 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 124, 67–76 (2011).

    Article  CAS  PubMed  Google Scholar 

  38. Vink, R. G. 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. (Lond.) 41, 722–728 (2017).

    Article  CAS  Google Scholar 

  39. Ellulu, M. S., Patimah, I., Khaza’ai, H., Rahmat, A. & Abed, Y. Obesity and inflammation: the linking mechanism and the complications. Arch. Med. Sci. 13, 851–863 (2017).

    Article  CAS  PubMed  Google Scholar 

  40. Domenis, R. et al. Pro inflammatory stimuli enhance the immunosuppressive functions of adipose mesenchymal stem cells-derived exosomes. Sci. Rep. 8, 13325 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Engin, A. B. Adipocyte-macrophage cross-talk in obesity. Adv. Exp. Med. Biol. 960, 327–343 (2017).

    Article  CAS  PubMed  Google Scholar 

  42. Fantuzzi, G. Adipose tissue, adipokines, and inflammation. J. Allergy Clin. Immunol. 115, 911–919 (2005).

    Article  CAS  PubMed  Google Scholar 

  43. Rosen, E. D. & Spiegelman, B. M. What we talk about when we talk about fat. Cell 156, 20–44 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kratz, M. et al. Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages. Cell Metab. 20, 614–625 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Alligier, M. et al. Subcutaneous adipose tissue remodeling during the initial phase of weight gain induced by overfeeding in humans. J. Clin. Endocrinol. Metab. 97, E183–E192 (2012).

    Article  CAS  PubMed  Google Scholar 

  46. Shimobayashi, M. et al. Insulin resistance causes inflammation in adipose tissue. J. Clin. Invest. 128, 1538–1550 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Maclean, P. S., Bergouignan, A., Cornier, M. A. & Jackman, M. R. Biology’s response to dieting: the impetus for weight regain. Am. J. Physiol. Regul. Integr. Comp. Physiol. 301, R581–R600 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Vink, R. G., Roumans, N. J., Arkenbosch, L. A., Mariman, E. C. & van Baak, M. A. The effect of rate of weight loss on long-term weight regain in adults with overweight and obesity. Obesity (Silver Spring) 24, 321–327 (2016).

    Article  CAS  Google Scholar 

  49. Lenz, M. et al. Estimating real cell size distribution from cross-section microscopy imaging. Bioinformatics 32, i396–i404 (2016).

    Article  CAS  PubMed  Google Scholar 

  50. Isakson, P., Hammarstedt, A., Gustafson, B. & Smith, U. Impaired preadipocyte differentiation in human abdominal obesity: role of Wnt, tumor necrosis factor-alpha, and inflammation. Diabetes 58, 1550–1557 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Rossmeislova, L. et al. Weight loss improves the adipogenic capacity of human preadipocytes and modulates their secretory profile. Diabetes 62, 1990–1995 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Vink, R. G., Roumans, N. J., Mariman, E. C. & van Baak, M. A. Dietary weight loss-induced changes in RBP4, FFA, and ACE predict weight regain in people with overweight and obesity. Physiol. Rep. 5, e13450 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Rosenbaum, M., Kissileff, H. R., Mayer, L. E., Hirsch, J. & Leibel, R. L. Energy intake in weight-reduced humans. Brain Res. 1350, 95–102 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Bouwman, F., Renes, J. & Mariman, E. A combination of protein profiling and isotopomer analysis using matrix-assisted laser desorption/ionization-time of flight mass spectrometry reveals an active metabolism of the extracellular matrix of 3T3-L1 adipocytes. Proteomics 4, 3855–3863 (2004).

    Article  CAS  PubMed  Google Scholar 

  55. Wang, P. et al. Insulin modulates the secretion of proteins from mature 3T3-L1 adipocytes: a role for transcriptional regulation of processing. Diabetologia 49, 2453–2462 (2006).

    Article  CAS  PubMed  Google Scholar 

  56. Mariman, E. C. & Wang, P. Adipocyte extracellular matrix composition, dynamics and role in obesity. Cell. Mol. Life Sci. 67, 1277–1292 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Rossmeislova, L., Malisova, L., Kracmerova, J. & Stich, V. Adaptation of human adipose tissue to hypocaloric diet. Int. J. Obes. (Lond.) 37, 640–650 (2013).

    Article  CAS  Google Scholar 

  58. Duncan, R. E., Ahmadian, M., Jaworski, K., Sarkadi-Nagy, E. & Sul, H. S. Regulation of lipolysis in adipocytes. Annu. Rev. Nutr. 27, 79–101 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Liu, Y. et al. Accumulation and changes in composition of collagens in subcutaneous adipose tissue after bariatric surgery. J. Clin. Endocrinol. Metab. 101, 293–304 (2016).

    Article  CAS  PubMed  Google Scholar 

  60. Schwarz, U. S. et al. Calculation of forces at focal adhesions from elastic substrate data: the effect of localized force and the need for regularization. Biophys. J. 83, 1380–1394 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Mutch, D. M. et al. A distinct adipose tissue gene expression response to caloric restriction predicts 6-mo weight maintenance in obese subjects. Am. J. Clin. Nutr. 94, 1399–1409 (2011).

    Article  CAS  PubMed  Google Scholar 

  62. Roumans, N. J. et al. Weight loss-induced stress in subcutaneous adipose tissue is related to weight regain. Br. J. Nutr. 115, 913–920 (2016).

    Article  CAS  PubMed  Google Scholar 

  63. Schneider, G. B., Hamano, H. & Cooper, L. F. In vivo evaluation of hsp27 as an inhibitor of actin polymerization: hsp27 limits actin stress fiber and focal adhesion formation after heat shock. J. Cell. Physiol. 177, 575–584 (1998).

    Article  CAS  PubMed  Google Scholar 

  64. Roumans, N. J. T. et al. Weight loss-induced cellular stress in subcutaneous adipose tissue and the risk for weight regain in overweight and obese adults. Int. J. Obes. (Lond.) 41, 894–901 (2017).

    Article  CAS  Google Scholar 

  65. Roumans, N. J. et al. Variation in extracellular matrix genes is associated with weight regain after weight loss in a sex-specific manner. Genes Nutr. 10, 56 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Veit, G. et al. Collagen XXIII, novel ligand for integrin α2β1 in the epidermis. J. Biol. Chem. 286, 27804–27813 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Schluterman, M. K. et al. Loss of fibulin-5 binding to β1 integrins inhibits tumor growth by increasing the level of ROS. Dis. Model. Mech. 3, 333–342 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Roumans, N. J., Vink, R. G., Fazelzadeh, P., van Baak, M. A. & Mariman, E. C. A role for leukocyte integrins and extracellular matrix remodeling of adipose tissue in the risk of weight regain after weight loss. Am. J. Clin. Nutr. 105, 1054–1062 (2017).

    Article  CAS  PubMed  Google Scholar 

  69. Roumans, N. J. T., Wang, P., Vink, R. G., van Baak, M. A. & Mariman, E. C. M. Combined analysis of stress- and ECM-related genes in their effect on weight regain. Obesity (Silver Spring) 26, 492–498 (2018).

    Article  CAS  Google Scholar 

  70. MacLean, P. S., Higgins, J. A., Giles, E. D., Sherk, V. D. & Jackman, M. R. The role for adipose tissue in weight regain after weight loss. Obes. Rev. 16 (Suppl. 1), 45–54 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Ge, F. et al. Facilitated long chain fatty acid uptake by adipocytes remains upregulated relative to BMI for more than a year after major bariatric surgical weight loss. Obesity (Silver Spring) 24, 113–122 (2016).

    Article  CAS  Google Scholar 

  72. Grenier-Larouche, T. et al. Fatty acid metabolic remodeling during type 2 diabetes remission after bariatric surgery. Diabetes 66, 2743–2755 (2017).

    Article  CAS  PubMed  Google Scholar 

  73. Bouwman, F. G., Wang, P., van Baak, M., Saris, W. H. & Mariman, E. C. Increased β-oxidation with improved glucose uptake capacity in adipose tissue from obese after weight loss and maintenance. Obesity (Silver Spring) 22, 819–827 (2014).

    Article  CAS  Google Scholar 

  74. Eastman, Q. Very low calorie diet makes adipocytes “scream”. J. Proteome Res. 8, 5408 (2009).

    Article  CAS  PubMed  Google Scholar 

  75. Vink, R. G. et al. Adipose tissue meal-derived fatty acid uptake before and after diet-induced weight loss in adults with overweight and obesity. Obesity (Silver Spring) 25, 1391–1399 (2017).

    Article  CAS  Google Scholar 

  76. Santosa, S., Hensrud, D. D., Votruba, S. B. & Jensen, M. D. The influence of sex and obesity phenotype on meal fatty acid metabolism before and after weight loss. Am. J. Clin. Nutr. 88, 1134–1141 (2008).

    Article  CAS  PubMed  Google Scholar 

  77. Johansson, L. E. et al. Differential gene expression in adipose tissue from obese human subjects during weight loss and weight maintenance. Am. J. Clin. Nutr. 96, 196–207 (2012).

    Article  CAS  PubMed  Google Scholar 

  78. Van Pelt, D. W., Guth, L. M., Wang, A. Y. & Horowitz, J. F. Factors regulating subcutaneous adipose tissue storage, fibrosis, and inflammation may underlie low fatty acid mobilization in insulin-sensitive obese adults. Am. J. Physiol. Endocrinol. Metab. 313, E429–E439 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Schwartz, A. & Doucet, E. Relative changes in resting energy expenditure during weight loss: a systematic review. Obes. Rev. 11, 531–547 (2010).

    Article  CAS  PubMed  Google Scholar 

  80. Camps, S. G., Verhoef, S. P. & Westerterp, K. R. Weight loss, weight maintenance, and adaptive thermogenesis. Am. J. Clin. Nutr. 97, 990–994 (2013).

    Article  CAS  PubMed  Google Scholar 

  81. Hall, K. D. & Kahan, S. Maintenance of lost weight and long-term management of obesity. Med. Clin. North Am. 102, 183–197 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Camps, S. G. et al. Weight loss-induced changes in adipose tissue proteins associated with fatty acid and glucose metabolism correlate with adaptations in energy expenditure. Nutr. Metab. (Lond.) 12, 37 (2015).

    Article  CAS  Google Scholar 

  83. Bouwman, F. G. et al. The physiologic effects of caloric restriction are reflected in the in vivo adipocyte-enriched proteome of overweight/obese subjects. J. Proteome Res. 8, 5532–5540 (2009).

    Article  CAS  PubMed  Google Scholar 

  84. Jokinen, R. et al. Adipose tissue mitochondrial capacity associates with long-term weight loss success. Int. J. Obes. (Lond.) 42, 817–825 (2017).

    Article  CAS  Google Scholar 

  85. Marquez-Quinones, A. et al. Adipose tissue transcriptome reflects variations between subjects with continued weight loss and subjects regaining weight 6 mo after caloric restriction independent of energy intake. Am. J. Clin. Nutr. 92, 975–984 (2010).

    Article  CAS  PubMed  Google Scholar 

  86. Chen, Y., Yang, J., Nie, X., Song, Z. & Gu, Y. Effects of bariatric surgery on change of brown adipocyte tissue and energy metabolism in obese mice. Obes. Surg. 28, 820–830 (2018).

    Article  PubMed  Google Scholar 

  87. Vijgen, G. H. et al. Increase in brown adipose tissue activity after weight loss in morbidly obese subjects. J. Clin. Endocrinol. Metab. 97, E1229–E1233 (2012).

    Article  CAS  PubMed  Google Scholar 

  88. Dadson, P. et al. Brown adipose tissue lipid metabolism in morbid obesity: effect of bariatric surgery-induced weight loss. Diabetes Obes. Metab. 20, 1280–1288 (2018).

    Article  CAS  PubMed  Google Scholar 

  89. Barquissau, V. et al. Caloric restriction and diet-induced weight loss do not induce browning of human subcutaneous white adipose tissue in women and men with obesity. Cell Rep. 22, 1079–1089 (2018).

    Article  CAS  PubMed  Google Scholar 

  90. Neinast, M. D. et al. Activation of natriuretic peptides and the sympathetic nervous system following Roux-en-Y gastric bypass is associated with gonadal adipose tissues browning. Mol. Metab. 4, 427–436 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Fabbiano, S. et al. Caloric restriction leads to browning of white adipose tissue through type 2 immune signaling. Cell Metab. 24, 434–446 (2016).

    Article  CAS  PubMed  Google Scholar 

  92. Zhang, Y. et al. Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432 (1994).

    Article  CAS  PubMed  Google Scholar 

  93. Siiteri, P. K. Adipose tissue as a source of hormones. Am. J. Clin. Nutr. 45, 277–282 (1987).

    Article  CAS  PubMed  Google Scholar 

  94. Wang, P., Mariman, E., Renes, J. & Keijer, J. The secretory function of adipocytes in the physiology of white adipose tissue. J. Cell. Physiol. 216, 3–13 (2008).

    Article  CAS  PubMed  Google Scholar 

  95. Choi, C. H. J. & Cohen, P. Adipose crosstalk with other cell types in health and disease. Exp. Cell Res. 360, 6–11 (2017).

    Article  CAS  PubMed  Google Scholar 

  96. Hocking, S. L., Wu, L. E., Guilhaus, M., Chisholm, D. J. & James, D. E. Intrinsic depot-specific differences in the secretome of adipose tissue, preadipocytes, and adipose tissue-derived microvascular endothelial cells. Diabetes 59, 3008–3016 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Strohacker, K., McCaffery, J. M., MacLean, P. S. & Wing, R. R. Adaptations of leptin, ghrelin or insulin during weight loss as predictors of weight regain: a review of current literature. Int. J. Obes. (Lond.) 38, 388–396 (2014).

    Article  CAS  Google Scholar 

  98. Wang, P. et al. Blood profile of proteins and steroid hormones predicts weight change after weight loss with interactions of dietary protein level and glycemic index. PLOS ONE 6, e16773 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Wang, P. et al. Circulating ACE is a predictor of weight loss maintenance not only in overweight and obese women, but also in men. Int. J. Obes. (Lond.) 36, 1545–1551 (2012).

    Article  CAS  Google Scholar 

  100. Rosenbaum, M. et al. Effects of weight change on plasma leptin concentrations and energy expenditure. J. Clin. Endocrinol. Metab. 82, 3647–3654 (1997).

    CAS  PubMed  Google Scholar 

  101. Tamez, M. et al. Adipocyte size and leptin receptor expression in human subcutaneous adipose tissue after Roux-en-Y gastric bypass. Obes. Surg. 27, 3330–3332 (2017).

    PubMed  Google Scholar 

  102. Bluher, M. & Mantzoros, C. S. From leptin to other adipokines in health and disease: facts and expectations at the beginning of the 21st century. Metabolism 64, 131–145 (2015).

    Article  CAS  PubMed  Google Scholar 

  103. Qi, Y. et al. Adiponectin acts in the brain to decrease body weight. Nat. Med. 10, 524–529 (2004).

    Article  CAS  PubMed  Google Scholar 

  104. Park, S., Kim, D. S., Kwon, D. Y. & Yang, H. J. Long-term central infusion of adiponectin improves energy and glucose homeostasis by decreasing fat storage and suppressing hepatic gluconeogenesis without changing food intake. J. Neuroendocrinol. 23, 687–698 (2011).

    Article  CAS  PubMed  Google Scholar 

  105. Smith, U. & Kahn, B. B. Adipose tissue regulates insulin sensitivity: role of adipogenesis, de novo lipogenesis and novel lipids. J. Intern. Med. 280, 465–475 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Noy, N. Vitamin A in regulation of insulin responsiveness: mini review. Proc. Nutr. Soc. 75, 212–215 (2016).

    Article  CAS  PubMed  Google Scholar 

  107. Brestoff, J. R. & Artis, D. Immune regulation of metabolic homeostasis in health and disease. Cell 161, 146–160 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Bernstein, K. E. et al. A modern understanding of the traditional and nontraditional biological functions of angiotensin-converting enzyme. Pharmacol. Rev. 65, 1–46 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. McGregor, R. A. & Choi, M. S. microRNAs in the regulation of adipogenesis and obesity. Curr. Mol. Med. 11, 304–316 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Hilton, C., Neville, M. J. & Karpe, F. MicroRNAs in adipose tissue: their role in adipogenesis and obesity. Int. J. Obes. (Lond.) 37, 325–332 (2013).

    Article  CAS  Google Scholar 

  111. Valenti, M. T., Dalle Carbonare, L. & Mottes, M. Role of microRNAs in progenitor cell commitment and osteogenic differentiation in health and disease (review). Int. J. Mol. Med. 41, 2441–2449 (2018).

    CAS  PubMed  Google Scholar 

  112. Zaragosi, L. E. et al. Small RNA sequencing reveals miR-642a-3p as a novel adipocyte-specific microRNA and miR-30 as a key regulator of human adipogenesis. Genome Biol. 12, R64 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Chen, S. Z. et al. The miR-181d-regulated metalloproteinase Adamts1 enzymatically impairs adipogenesis via ECM remodeling. Cell Death Differ. 23, 1778–1791 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Liu, W. et al. LncRNA Gm15290 sponges miR-27b to promote PPARgamma-induced fat deposition and contribute to body weight gain in mice. Biochem. Biophys. Res. Commun. 493, 1168–1175 (2017).

    Article  CAS  PubMed  Google Scholar 

  115. Karbiener, M. et al. MicroRNA-26 family is required for human adipogenesis and drives characteristics of brown adipocytes. Stem Cells 32, 1578–1590 (2014).

    Article  CAS  PubMed  Google Scholar 

  116. Engin, A. B. MicroRNA and adipogenesis. Adv. Exp. Med. Biol. 960, 489–509 (2017).

    Article  CAS  PubMed  Google Scholar 

  117. Belarbi, Y. et al. MicroRNAs-361-5p and miR-574-5p associate with human adipose morphology and regulate EBF1 expression in white adipose tissue. Mol. Cell. Endocrinol. 472, 50–56 (2017).

    Article  PubMed  CAS  Google Scholar 

  118. Fatima, F. & Nawaz, M. Long distance metabolic regulation through adipose-derived circulating exosomal miRNAs: a trail for RNA-based therapies? Front. Physiol. 8, 545 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  119. Arner, P. & Kulyte, A. MicroRNA regulatory networks in human adipose tissue and obesity. Nat. Rev. Endocrinol. 11, 276–288 (2015).

    Article  CAS  PubMed  Google Scholar 

  120. Arner, E. et al. Adipose tissue microRNAs as regulators of CCL2 production in human obesity. Diabetes 61, 1986–1993 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Zhu, L. et al. MiR-335, an adipogenesis-related microRNA, is involved in adipose tissue inflammation. Cell Biochem. Biophys. 68, 283–290 (2014).

    Article  CAS  PubMed  Google Scholar 

  122. Ortega, F. J. et al. Surgery-induced weight loss is associated with the downregulation of genes targeted by MicroRNAs in adipose tissue. J. Clin. Endocrinol. Metab. 100, E1467–E1476 (2015).

    Article  CAS  PubMed  Google Scholar 

  123. Schroeder, M., Drori, Y., Ben-Efraim, Y. J. & Chen, A. Hypothalamic miR-219 regulates individual metabolic differences in response to diet-induced weight cycling. Mol. Metab. 9, 176–186 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Bollepalli, S. et al. Subcutaneous adipose tissue gene expression and DNA methylation respond to both short- and long-term weight loss. Int. J. Obes. (Lond.) 42, 412–423 (2018).

    Article  CAS  Google Scholar 

  125. Martinez, J. A., Milagro, F. I., Claycombe, K. J. & Schalinske, K. L. Epigenetics in adipose tissue, obesity, weight loss, and diabetes. Adv. Nutr. 5, 71–81 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Maurizi, G., Della Guardia, L., Maurizi, A. & Poloni, A. Adipocytes properties and crosstalk with immune system in obesity-related inflammation. J. Cell. Physiol. 233, 88–97 (2018).

    Article  CAS  PubMed  Google Scholar 

  127. Capel, F. 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. 93, 4315–4322 (2008).

    Article  CAS  PubMed  Google Scholar 

  128. Vink, R. G. et al. Adipose tissue gene expression is differentially regulated with different rates of weight loss in overweight and obese humans. Int. J. Obes. (Lond.) 41, 309–316 (2017).

    Article  CAS  Google Scholar 

  129. Capel, F. et al. Macrophages and adipocytes in human obesity: adipose tissue gene expression and insulin sensitivity during calorie restriction and weight stabilization. Diabetes 58, 1558–1567 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Schmitz, J. et al. Obesogenic memory can confer long-term increases in adipose tissue but not liver inflammation and insulin resistance after weight loss. Mol. Metab. 5, 328–339 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Snel, M. et al. Immediate and long-term effects of addition of exercise to a 16-week very low calorie diet on low-grade inflammation in obese, insulin-dependent type 2 diabetic patients. Food Chem. Toxicol. 49, 3104–3111 (2011).

    Article  CAS  PubMed  Google Scholar 

  132. Malisova, L. et al. Expression of inflammation-related genes in gluteal and abdominal subcutaneous adipose tissue during weight-reducing dietary intervention in obese women. Physiol. Res. 63, 73–82 (2014).

    Article  CAS  PubMed  Google Scholar 

  133. Zou, J. et al. CD4+T cells memorize obesity and promote weight regain. Cell. Mol. Immunol. 15, 630–639 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  134. Kong, L. C. et al. Insulin resistance and inflammation predict kinetic body weight changes in response to dietary weight loss and maintenance in overweight and obese subjects by using a Bayesian network approach. Am. J. Clin. Nutr. 98, 1385–1394 (2013).

    Article  CAS  PubMed  Google Scholar 

  135. Wang, H. & Ye, J. Regulation of energy balance by inflammation: common theme in physiology and pathology. Rev. Endocr. Metab. Disord. 16, 47–54 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. van den Berg, S. M., van Dam, A. D., Rensen, P. C., de Winther, M. P. & Lutgens, E. Immune modulation of brown(ing) adipose tissue in obesity. Endocr. Rev. 38, 46–68 (2017).

    Article  PubMed  Google Scholar 

  137. Armenise, C. et al. Transcriptome profiling from adipose tissue during a low-calorie diet reveals predictors of weight and glycemic outcomes in obese, nondiabetic subjects. Am. J. Clin. Nutr. 106, 736–746 (2017).

    CAS  PubMed  Google Scholar 

  138. Sumithran, P., Purcell, K., Kuyruk, S., Proietto, J. & Prendergast, L. A. Combining biological and psychosocial baseline variables did not improve prediction of outcome of a very-low-energy diet in a clinic referral population. Clin. Obes. 8, 30–38 (2018).

    Article  CAS  PubMed  Google Scholar 

  139. Caires, R. et al. Omega-3 fatty acids modulate TRPV4 function through plasma membrane remodeling. Cell Rep. 21, 246–258 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Sidossis, L. & Kajimura, S. Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis. J. Clin. Invest. 125, 478–486 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  141. Shen, W. & McIntosh, M. K. Nutrient regulation: conjugated linoleic acid’s inflammatory and browning properties in adipose tissue. Annu. Rev. Nutr. 36, 183–210 (2016).

    Article  CAS  PubMed  Google Scholar 

  142. Tsiloulis, T. et al. No evidence of white adipocyte browning after endurance exercise training in obese men. Int. J. Obes. (Lond.) 42, 721–727 (2017).

    Article  CAS  Google Scholar 

  143. Norheim, F. et al. The effects of acute and chronic exercise on PGC-1alpha, irisin and browning of subcutaneous adipose tissue in humans. FEBS J. 281, 739–749 (2014).

    Article  CAS  PubMed  Google Scholar 

  144. Nakhuda, A. et al. Biomarkers of browning of white adipose tissue and their regulation during exercise- and diet-induced weight loss. Am. J. Clin. Nutr. 104, 557–565 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Pino, M. F., Parsons, S. A., Smith, S. R. & Sparks, L. M. Active individuals have high mitochondrial content and oxidative markers in their abdominal subcutaneous adipose tissue. Obesity (Silver Spring) 24, 2467–2470 (2016).

    Article  CAS  Google Scholar 

  146. Steig, A. J. et al. Exercise reduces appetite and traffics excess nutrients away from energetically efficient pathways of lipid deposition during the early stages of weight regain. Am. J. Physiol. Regul. Integr. Comp. Physiol. 301, R656–R667 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Giles, E. D. et al. Exercise decreases lipogenic gene expression in adipose tissue and alters adipocyte cellularity during weight regain after weight loss. Frontiers Physiol. 7, 32 (2016).

    Article  Google Scholar 

  148. Bartus, R. T. et al. β2-adrenoceptor agonists as novel, safe and potentially effective therapies for amyotrophic lateral sclerosis (ALS). Neurobiol. Dis. 85, 11–24 (2016).

    Article  CAS  PubMed  Google Scholar 

  149. Esser, N., Paquot, N. & Scheen, A. J. Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease. Expert Opin. Investig. Drugs 24, 283–307 (2015).

    Article  CAS  PubMed  Google Scholar 

  150. Poulsen, M. M. et al. Resveratrol and inflammation: challenges in translating pre-clinical findings to improved patient outcomes. Biochim. Biophys. Acta 1852, 1124–1136 (2015).

    Article  CAS  PubMed  Google Scholar 

  151. Gleeson, M. et al. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat. Rev. Immunol. 11, 607–615 (2011).

    Article  CAS  PubMed  Google Scholar 

  152. Lancaster, G. I. & Febbraio, M. A. The immunomodulating role of exercise in metabolic disease. Trends Immunol. 35, 262–269 (2014).

    Article  CAS  PubMed  Google Scholar 

  153. Auerbach, P. et al. Differential effects of endurance training and weight loss on plasma adiponectin multimers and adipose tissue macrophages in younger, moderately overweight men. Am. J. Physiol. Regul. Integr. Comp. Physiol. 305, R490–R498 (2013).

    Article  CAS  PubMed  Google Scholar 

  154. van Baak, M. A. et al. Leisure-time activity is an important determinant of long-term weight maintenance after weight loss in the Sibutramine Trial on Obesity Reduction and Maintenance (STORM trial). Am. J. Clin. Nutr. 78, 209–214 (2003).

    Article  PubMed  Google Scholar 

  155. Kerns, J. C. et al. Increased physical activity associated with less weight regain six years after “the biggest loser” competition. Obesity (Silver Spring) 25, 1838–1843 (2017).

    Article  Google Scholar 

  156. Ostendorf, D. M. et al. Objectively measured physical activity and sedentary behavior in successful weight loss maintainers. Obesity (Silver Spring) 26, 53–60 (2018).

    Article  Google Scholar 

  157. de Luis, D. A. et al. Biochemical, anthropometric and lifestyle factors related with weight maintenance after weight loss secondary to a hypocaloric mediterranean diet. Ann. Nutr. Metab. 71, 217–223 (2017).

    Article  PubMed  CAS  Google Scholar 

  158. Kjaer, T. N. et al. Resveratrol reduces the levels of circulating androgen precursors but has no effect on, testosterone, dihydrotestosterone, PSA levels or prostate volume. A 4-month randomised trial in middle-aged men. Prostate 75, 1255–1263 (2015).

    Article  CAS  PubMed  Google Scholar 

  159. Calder, P. C. Long-chain fatty acids and inflammation. Proc. Nutr. Soc. 71, 284–289 (2012).

    Article  PubMed  CAS  Google Scholar 

  160. Shivappa, N. et al. Associations between dietary inflammatory index and inflammatory markers in the Asklepios Study. Br. J. Nutr. 113, 665–671 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Shivappa, N., Steck, S. E., Hurley, T. G., Hussey, J. R. & Hebert, J. R. Designing and developing a literature-derived, population-based dietary inflammatory index. Publ. Health Nutr. 17, 1689–1696 (2014).

    Article  Google Scholar 

  162. Ramallal, R. et al. Inflammatory potential of diet, weight gain, and incidence of overweight/obesity: the SUN Cohort. Obesity 25, 997–1005 (2017).

    Article  PubMed  Google Scholar 

  163. Muhammad, H. F. L. et al. Dietary intake after weight loss and the risk of weight regain: macronutrient composition and inflammatory properties of the diet. Nutrients 9, 1205 (2017).

    Article  PubMed Central  CAS  Google Scholar 

  164. Ravussin, E. et al. Enhanced weight loss with pramlintide/metreleptin: an integrated neurohormonal approach to obesity pharmacotherapy. Obesity (Silver Spring) 17, 1736–1743 (2009).

    Article  CAS  Google Scholar 

  165. Aller, E. E. et al. Weight loss maintenance in overweight subjects on ad libitum diets with high or low protein content and glycemic index: the DIOGENES trial 12-month results. Int. J. Obes. (Lond.) 38, 1511–1517 (2014).

    Article  CAS  Google Scholar 

  166. Johansson, K., Neovius, M. & Hemmingsson, E. Effects of anti-obesity drugs, diet, and exercise on weight-loss maintenance after a very-low-calorie diet or low-calorie diet: a systematic review and meta-analysis of randomized controlled trials. Am. J. Clin. Nutr. 99, 14–23 (2014).

    Article  CAS  PubMed  Google Scholar 

  167. The STORM Study Group. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. Lancet 356, 2119–2125 (2000).

    Article  Google Scholar 

  168. Richelsen, B. et al. Effect of orlistat on weight regain and cardiovascular risk factors following a very-low-energy diet in abdominally obese patients: a 3-year randomized, placebo-controlled study. Diabetes Care 30, 27–32 (2007).

    Article  CAS  PubMed  Google Scholar 

  169. Wadden, T. A. et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int. J. Obes. (Lond.) 37, 1443–1451 (2013).

    Article  CAS  Google Scholar 

  170. Vazquez, C. et al. Meal replacement with a low-calorie diet formula in weight loss maintenance after weight loss induction with diet alone. Eur. J. Clin. Nutr. 63, 1226–1232 (2009).

    Article  CAS  PubMed  Google Scholar 

  171. Westerterp-Plantenga, M. S., Lejeune, M. P. & Kovacs, E. M. Body weight loss and weight maintenance in relation to habitual caffeine intake and green tea supplementation. Obes. Res. 13, 1195–1204 (2005).

    Article  CAS  PubMed  Google Scholar 

  172. Dutton, G. R. et al. Comparison of an alternative schedule of extended care contacts to a self-directed control: a randomized trial of weight loss maintenance. Int. J. Behav. Nutr. Phys. Act. 14, 107 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  173. Voils, C. I. et al. Maintenance of weight loss after initiation of nutrition training: a randomized trial. Ann. Intern. Med. 166, 463–471 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  174. Crain, A. L., Sherwood, N. E., Martinson, B. C. & Jeffery, R. W. Mediators of weight loss maintenance in the Keep It Off trial. Ann. Behav. Med. 52, 9–18 (2017).

    Article  PubMed Central  Google Scholar 

  175. Ryan, A. S., Serra, M. C. & Goldberg, A. P. Metabolic benefits of prior weight loss with and without exercise on subsequent 6-month weight regain. Obesity (Silver Spring) 26, 37–44 (2018).

    Article  CAS  Google Scholar 

  176. Wong, M. H. et al. Caloric restriction induces changes in insulin and body weight measurements that are inversely associated with subsequent weight regain. PLOS ONE 7, e42858 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Hanvold, S. E. et al. Plasma amino acids, adiposity, and weight change after gastric bypass surgery: are amino acids associated with weight regain? Eur. J. Nutr. 57, 2629–2637 (2017).

    Article  PubMed  CAS  Google Scholar 

  178. Sawamoto, R. et al. Predictors of successful long-term weight loss maintenance: a two-year follow-up. Biopsychosoc. Med. 11, 14 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  179. Calugi, S., Marchesini, G., El Ghoch, M., Gavasso, I. & Dalle Grave, R. The influence of weight-loss expectations on weight loss and of weight-loss satisfaction on weight maintenance in severe obesity. J. Acad. Nutr. Diet 117, 32–38 (2017).

    Article  PubMed  Google Scholar 

  180. Greenberg, I., Stampfer, M. J., Schwarzfuchs, D., Shai, I. & Group, D. Adherence and success in long-term weight loss diets: the dietary intervention randomized controlled trial (DIRECT). J. Am. Coll. Nutr. 28, 159–168 (2009).

    Article  CAS  PubMed  Google Scholar 

  181. Vogels, N. & Westerterp-Plantenga, M. S. Categorical strategies based on subject characteristics of dietary restraint and physical activity, for weight maintenance. Int. J. Obes. (Lond.) 29, 849–857 (2005).

    Article  CAS  Google Scholar 

  182. Fabricatore, A. N. et al. Predictors of attrition and weight loss success: results from a randomized controlled trial. Behav. Res. Ther. 47, 685–691 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  183. Lillis, J. et al. Weight loss intervention for individuals with high internal disinhibition: design of the Acceptance Based Behavioral Intervention (ABBI) randomized controlled trial. BMC Psychol. 3, 17 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  184. Butryn, M. L., Thomas, J. G. & Lowe, M. R. Reductions in internal disinhibition during weight loss predict better weight loss maintenance. Obesity (Silver Spring) 17, 1101–1103 (2009).

    Article  Google Scholar 

  185. Abu Dayyeh, B. K., Jirapinyo, P. & Thompson, C. C. Plasma ghrelin levels and weight regain after Roux-en-Y gastric bypass surgery. Obes. Surg. 27, 1031–1036 (2017).

    Article  PubMed  Google Scholar 

  186. Brock, D. W. et al. Perception of exercise difficulty predicts weight regain in formerly overweight women. Obesity (Silver Spring) 18, 982–986 (2010).

    Article  Google Scholar 

  187. Price, D. W. et al. Depression as a predictor of weight regain among successful weight losers in the diabetes prevention program. Diabetes Care 36, 216–221 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  188. Larsen, L. H. et al. Analyses of single nucleotide polymorphisms in selected nutrient-sensitive genes in weight-regain prevention: the DIOGENES study. Am. J. Clin. Nutr. 95, 1254–1260 (2012).

    Article  CAS  PubMed  Google Scholar 

  189. Nicklas, B. J. et al. Genetic variation in the peroxisome proliferator-activated receptor-gamma2 gene (Pro12Ala) affects metabolic responses to weight loss and subsequent weight regain. Diabetes 50, 2172–2176 (2001).

    Article  CAS  PubMed  Google Scholar 

  190. McCaffery, J. M. et al. FTO predicts weight regain in the Look AHEAD clinical trial. Int. J. Obes. (Lond.) 37, 1545–1552 (2013).

    Article  CAS  Google Scholar 

  191. Delahanty, L. M. et al. Genetic predictors of weight loss and weight regain after intensive lifestyle modification, metformin treatment, or standard care in the Diabetes Prevention Program. Diabetes Care 35, 363–366 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Masuo, K. et al. Rebound weight gain as associated with high plasma norepinephrine levels that are mediated through polymorphisms in the β2-adrenoceptor. Am. J. Hypertens. 18, 1508–1516 (2005).

    Article  CAS  PubMed  Google Scholar 

  193. Crujeiras, A. B. et al. Association of weight regain with specific methylation levels in the NPY and POMC promoters in leukocytes of obese men: a translational study. Regul. Pept. 186, 1–6 (2013).

    Article  CAS  PubMed  Google Scholar 

Download references

Reviewer information

Nature Reviews Endocrinology thanks José Fernandez-Real and other anonymous reviewers for their contribution to the peer review of this work.

Author information

Authors and Affiliations

  1. NUTRIM School for Nutrition and Translational Research in Metabolism, Department of Human Biology, Maastricht University, Maastricht, Netherlands

    Marleen A. van Baak & Edwin C. M. Mariman

Authors
  1. Marleen A. van Baak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Edwin C. M. Mariman
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to Marleen A. van Baak.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

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

Glossary

Energy balance

The balance between energy intake and energy expenditure.

Fasting fatty acid rate of appearance

The rate of release of fattyacids into the plasma in thefasting state, which can bedetermined by measuring thedilution of an infused fatty acidtracer in plasma.

Weight cycling

The repeated loss and regain of body weight.

Bayesian analysis

A statistical paradigm that answers research questions about unknown parameters using probability statements.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

van Baak, M.A., Mariman, E.C.M. Mechanisms of weight regain after weight loss — the role of adipose tissue. Nat Rev Endocrinol 15, 274–287 (2019). https://doi.org/10.1038/s41574-018-0148-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41574-018-0148-4

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing