Abstract
Obesity, often referred to as the "tsunami of the 21st century", is a chronic, incurable disease prone to relapses. The crucial intervention aimed at reducing body weight for health benefits is lifestyle modification, but unfortunately, in most cases after the initial period of weight loss, a recurrence of overweight or obesity is observed. A similar process occurs in patients after bariatric surgery. It should be understood that the reason for this phenomenon does not necessarily must be associated with the lack of the patient adherence, but is a consequence of the activation of a strong objective mechanism - metabolic adaptation, i.e. changes in energy homeostasis to counteract lossing of energy. The article briefly describes the most important mechanisms of metabolic adaptation and presents the ways to counteract it.
References
Olszaniecka-Glinianowicz M, Mazur A, Chudek J, et al. Obesity in Adults: Position Statement of Polish Association for the Study on Obesity, Polish Association of Endocrinology, Polish Association of Cardiodiabetology, Polish Psychiatric Association, Section of Metabolic and Bariatric Surgery of the Association of Polish Surgeons, and the College of Family Physicians in Poland. Nutrients 2023; 15:1641. doi.org/10.3390/nu15071641.
Badman MK, Flier JS. The gut and energy balance: visceral allies in the obesity wars. Science 2005; 307(5717):1909-14. DOI:10.1126/science.1109951.
Theilade S, Christensen MB, Vilsbøll T, et al. An overview of obesity mechanisms in humans: Endocrine regulation of food intake, eating behavior and common determinants of body weight. Diabetes Obes Metab 2021; 23(Supp.1):17-35. DOI:10.1111/dom.14270.
Martinez JA. Body-weight regulation: causes of obesity. Proc Nutr Soc 2000; 59(3):337-45. DOI:10.1017/s0029665100000380.
Gainetdinov RR. Mesolimbic dopamine in obesity and diabetes. Am J Physiol Regul Integr Comp Physiol 2007; 293(2):R601-2. DOI:10.1152/ajpregu.00450.2007.
Naef L, Pitman KA, Borgland SL. Mesolimbic dopamine and its neuromodulators in obesity and binge eating. CNS Spectr 2015; 20(6):574-83. DOI:10.1017/S1092852915000693.
Martínez-Gómez MG, Roberts BM. Metabolic Adaptations to Weight Loss: A Brief Review. J Strength Cond Res 2022; 36(10):2970-2981. DOI:10.1519/JSC.0000000000003991.
Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes Metab 2022; 24 (8):1553-64.
Weintraub MA, D’Angelo D, Tchang BG, et. al. Five-year weight loss maintenance with obesity pharmacotherapy. J Clin Endocrinol Metab 2023; 108(9):e832-41.
Quarenghi M, Capelli S, Galligani G, et al. Weight Regain After Liraglutide, Semaglutide or Tirzepatide Interruption: A Narrative Review of Randomized Studies. J Clin Med 2025; 14(11):3791. DOI:10.3390/jcm14113791.
Noria SF, Shelby RD, Atkins KD, et al. Weight Regain After Bariatric Surgery: Scope of the Problem, Causes, Prevention, and Treatment. Curr Diab Rep 2023; 23(3):31-42. DOI:10.1007/s11892-023-01498-z.
Cooper TC, Simmons EB, Webb K, et al. Trends in weight regain following Roux-en-Y gastric bypass(RYGB) bariatric surgery. Obes Surg 2015; 25(8):1474-81. doi.org/10. 1007/s11695- 014- 1560-z.
Lauti M, Kularatna M, Hill AG, et al. Weight regain following sleeve gastrectomy-a systematic review. Obes Surg 2016; 26(6):1326-34. doi.org/10.1007/s11695-016-2152-x.
King WC, Hinerman AS, Belle SH, et al. Comparison of the performance of common measures of weight regain after bariatric surgery for association with clinical outcomes. JAMA 2018; 320(15):1560-9. https:/doi.org/10.1001/.
Müller MJ, Enderle J, Pourhassan M, et al. Metabolic adaptation to caloric restriction and subsequent refeeding: the Minnesota Starvation Experiment revisited. Am J Clin Nutr 2015; 102(4):807-19. DOI:10.3945/ajcn.115.109173.
Dabas J, Shunmukha Priya S, Alawani A, et al. What could be the reasons for not losing weight even after following a weight loss program? J Health Popul Nutr 2024; 43(1):37. DOI:10.1186/s41043-024-00516-4.
Schwartz A, Doucet E. Relative changes in resting energy expenditure during weight loss: a systematic review. Obes Rev 2010; 11(7):531-47. DOI:10.1111/j.1467-789X.2009.00654.x.
McInnis K, Brown JL, Finlayson G, et al. Appetite Changes in Weight Regain and Weight Maintenance After Roux-en-Y Gastric Bypass. Obes Surg 2022; 32(7):1-12. DOI:10.1007/s11695-022-06061-5.
Most J, Redman LM. Impact of calorie restriction on energy metabolism in humans. Exp Gerontol 2020; 133:110875. DOI:10.1016/j.exger.2020.110875.
Catenacci VA, Pan Z, Ostendorf D, et al. A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity. Obesity (Silver Spring) 2016; 24(9):1874-83. DOI:10.1002/oby.21581.
Stekovic S, Hofer SJ, Tripolt N, et al. Alternate Day Fasting Improves Physiological and Molecular Markers of Aging in Healthy, Non-obese Humans. Cell Metab 2019; 30(3):462-476.e6. DOI:10.1016/j.cmet.2019.07.016.
Busetto L, Bettini S, Makaronidis J, et al. Mechanisms of weight gain. Eur J Int Med 2021; 93:3-7.
Aronne LJ, Hall KD, Jakicic MJ, et al. Describing the Weight-Reduced State: Physiology, Behavior, and Interventions. Obesity (Silver Spring) 2021; 29(Supp. 1):S9-S24. DOI:10.1002/oby.23086.
Rosenbaum M, Goldsmith RL, Haddad F, et al. Triiodothyronine and leptin repletion in humans similarly reverse weight-loss-induced changes in skeletal muscle. Am J Physiol Endocrinol Metab 2018; 315(5):E771-E779. DOI:10.1152/ajpendo.00116.2018.
Löffler MC, Betz MJ, Blondin DP, et al. Challenges in tackling energy expenditure as obesity therapy: From preclinical models to clinical application. Mol Metab 2021; 51:101237. DOI:10.1016/j.molmet.2021.101237.
Bilski J, Pierzchalski P, Szczepanik M, et al. Multifactorial Mechanism of Sarcopenia and Sarcopenic Obesity. Role of Physical Exercise, Microbiota and Myokines. Cells 2022; 11:160. doi.org/10.3390/cells11010160.
Hunter GR, Singh H, Carter SJ, et al. Sarcopenia and Its Implications for Metabolic Health. J Obes 2019; 8031705. DOI:10.1155/2019/8031705.
Caturano A, Amaro A, Berra CC, et al. Sarcopenic obesity and weight loss-induced muscle mass loss. Curr Opin Clin Nutr Metab Care 2025; 28:339-350. DOI:10.1097/MCO.0000000000001131.
Kokura Y, Ueshima J, Saino Y, Maeda K. Enhanced protein intake on maintaining muscle mass, strength, and physical function in adults with overweight/obesity: a systematic review and meta-analysis. Clin Nutr ESPEN 2024; 63:417-426.
Smith GI, Yoshino J, Kelly SC, et al. High-protein intake during weight loss therapy eliminates the weight-loss-induced improvement in insulin action in obese postmenopausal women. Cell Rep 2016; 17:849-861.
Batsis JA, Batchek DJ, Petersen CL, et al. Protein supplementation may dampen positive effects of exercise on glucose homeostasis: a pilot weight loss intervention. Nutrients 2023; 15(23):4947. DOI:10.3390/nu15234947.
Hunter GR, Bickel CS, Fisher G, et al. Combined aerobic/strength training and energy expenditure in older women. Med Sci Sports Exerc 2013; 45(7):1386-93. DOI:10.1249/MSS.0b013e3182860099.
Bąk-Sosnowska M, Białkowska M, Bogdański P, i wsp. Zalecenia kliniczne dotyczące postępowania u chorych na otyłość 2024. Stanowisko Polskiego Towarzystwa Leczenia Otyłości. Medycyna Praktyczna. Wydanie specjalne, Wrzesień 2024.
Mousavi A, Shojaei S, Azarboo A, et al. The role of glucagon-like peptide-1 receptor agonists in weight regain treatment or prevention after bariatric surgery: a systematic review and meta-analysis. Eat Weight Disord 2025; 30(1):70. DOI:10.1007/s40519-025-01770-z.
Çalık Başaran N, Dotan I, Dicker D. Post metabolic bariatric surgery weight regain: the importance of GLP-1 levels. Int J Obes (Lond) 2025; 49(3):412-417. DOI:10.1038/s41366-024-01461-2.
Wharton S, Yin P, Burrows M, et al. Extended-release naltrexone/bupropion is safe and effective among subjects with type 2 diabetes already taking incretin agents: a post-hoc analysis of the LIGHT trial. Int J Obes (Lond) 2021; 45(8):1687-1695. DOI:10.1038/s41366-021-00831-4.
Dechelotte P, Breton J, Trotin-Picolo C, et al. The Probiotic Strain H. alvei HA4597® Improves Weight Loss in Overweight Subjects under Moderate Hypocaloric Diet: A Proof-of-Concept, Multicenter Randomized, Double-Blind Placebo-Controlled Study. Nutrients 2021; 13:1902. doi.org/10.3390/nu13061902.
Kang CH, Jung ES, Jung SJ, et al. Pasteurized Akkermansia muciniphila HB05 (HB05P) Improves Muscle Strength and Function: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients 2024; 16:4037. doi.org/10.3390/nu16234037.
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