Treatment of obesity and physiological regulationNew findings on the set-point theoryArticle in several languages: deutsch | English
29 December 2017 (online)
According to the World Health Organization (WHO), the number of obese persons worldwide increases constantly, and a downwards trend is not in sight. The body weight is stabilized by hormonal and neurochemical processes, and attempts to reduce the body weight fail in most persons. After an initially successful weight reduction, significant weight regain over subsequent years to the level of its previous “set-point” is nearly universal. Only a detailed knowledge about the precise mechanism of body weight regulation can open up the field of research for sustainably acting treatments for obesity. Results from current research suggest that the “set-point” is stored in hypothalamic regions of the brain, which is ‘defended’ by neurochemical processes triggered by weight loss. This seems to be the main reasons why, in the long-term, weight regain is more likely to occur than weight loss. To understand the mechanisms why in some persons any attempts to reduce weight permanently fail, while others remain lean, is one of the key areas of current obesity research. The present article gives an overview of the current state of research in the field of set-point theory.
- 1 Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J. et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999; 257 (01) 79-83.
- 2 Badman MK, Flier JS. The gut and energy balance: visceral allies in the obesity wars. Science 2005; 307 5717 1909-1914.
- 3 Batterham RL, Le Roux CW, Cohen MA, Park AJ, Ellis SM, Patterson M. et al. Pancreatic polypeptide reduces appetite and food intake in humans. J Clin Endocrinol Metab 2003; 88 (08) 3989-3992.
- 4 Bray GA, Frühbeck G, Ryan DH, Wilding JP. Management of obesity. Lancet 2016; 387 10031 1947-1956.
- 5 Chelikani PK, Haver AC, Reidelberger RD. Intravenous infusion of peptide YY(3–36) potently inhibits food intake in rats. Endocrinology 2005; 146 (02) 879-888.
- 6 Chhabra KH, Adams JM, Jones GL, Yamashita M, Schlapschy M, Skerra A. et al. Reprogramming the body weight set point by a reciprocal interaction of hypothalamic leptin sensitivity and Pomc gene expression reverts extreme obesity. Mol Metab 2016; 05 (10) 869-881.
- 7 Clark A, Nilsson MR. Islet amyloid: a complication of islet dysfunction or an aetiological factor in Type 2 diabetes?. Diabetologia 2004; 47 (02) 157-169.
- 8 De Jonghe BC, Hayes MR, Bence KK. Melanocortin control of energy balance: evidence from rodent models. Cellular and Molecular Life Sciences 2011; 68 (15) 2569e-2588.
- 9 Deutsche Adipositas Gesellschaft (DAG). Interdisziplinäre Leitlinie der Qualität S3 zur Prävention und Therapie der Adipositas, Version 2.0 (April 2014). URL: http://www.adipositas-gesellschaft.de/fileadmin/PDF/Leitlinien/050–001l_S3_Adipositas_Praevention_Therapie_2014–11.pdf [letzter Zugriff am 7.11.2016].
- 10 Doucet E, Imbeault P, St-Pierre S, Alméras N, Mauriège P, Richard D, Tremblay A. Appetite after weight loss by energy restriction and a low-fat diet-exercise follow-up. Int J Obes Relat Metab Disord 2000; 24 (07) 906-914.
- 11 Drucker DJ, Nauck MA. The Incretin System: Glucagon-like Peptide-1 Receptor Agonists and Dipeptidyl peptidase-4 Inhibitors in Type 2 Diabetes. 2006; 368: 1696-1705.
- 12 EMA Draft Guideline on clinical evaluation of medicinal products used in weight control EMA/ CHMP/3118, 26 June 2014. Verfügbar unter: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/07/WC500170278.pdf [letzter Zugriff am 7.11.2016].
- 13 Ferguson C, David S, Divine L. et al. George Washington University, School of Public Health and Health Services, Department of Health Policy. Obesity Drug Outcome Measures: A Consensus Report of Considerations Regarding Pharmacologic Intervention. https://publichealth.gwu.edu/pdf/obesitydrugmeasures.pdf (letzter Zugriff 7.11.2016].
- 14 Gault VA, O’Harte FP, Flatt PR. Glucose-dependent insulinotropic polypeptide (GIP): anti-diabetic and anti-obesity potential?. Neuropeptides 2003; 37 (05) 253-263.
- 15 Greenberg JA, Boozer CN. The leptin-fat ratio is constant, and leptin may be part of two feedback mechanisms for maintaining the body fat set point in non-obese male Fischer 344 rats. Horm Metab Res 1999; 31 (09) 525-532.
- 16 Kälin S, Heppner FL, Bechmann I, Prinz M, Tschöp MH, Yi CX. Hypothalamic innate immune reaction in obesity. Nat Rev Endocrinol 2015; Jun 11 (06) 339-351.
- 17 Kennedy GC. The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc Lond B Biol Sci 1953; 140 (901) 578-596.
- 18 Kim YJ, Bi S. Knockdown of neuropeptide Y in the dorsomedial hypothalamus reverses high-fat dietinduced obesity and impaired glucose tolerance in rats. Am J Physiol Regul Integr Comp Physiol 2016; Jan 15 310 (02) R134-142.
- 19 Levin BE, Keesey RE. Defense of differing body weight set points in diet-induced obese and resistant rats. Am J Physiol 1998; 274 2 Pt 2 R412-419.
- 20 Luchtman DW, Chee MJ, Doslikova B, Marks DL, Baracos VE, Colmers WF. Defense of Elevated Body Weight Setpoint in Diet-Induced Obese Rats on Low Energy Diet Is Mediated by Loss of Melanocortin Sensitivity in the Paraventricular Hypothalamic Nucleus. PLoS One 2015; 10 (10) e0139462.
- 21 Mann T, Tomiyama AJ, Westling E, Lew AM, Samuels B, Chatman J. Medicare’s search for effective obesity treatments: diets are not the answer. Am Psychol 2007; 62 (03) 220-233.
- 22 Marx J. Cellular warriors at the battle of the bulge. Science 2003; 299 5608 846-849.
- 23 McTernan PG, Kusminski CM, Kumar S. Resistin. Curr Opin Lipidol 2006; 17 (02) 170-175.
- 24 OECD. 2014 Health at a Glance: Europe 2014. OECD Publishing. Verfügbar unter: http://dx.doi.org/10.1787/health_glance_eur-2014-en [letzter Zugriff am 7.11.2016]
- 25 OECD Obesity update. 2014 verfügbar unter: http://www.oecd.org/els/health-systems/Obesity- Update-2014.pdf [letzter Zugriff am 7.11.2016].
- 26 Sakata I, Nakamura K, Yamazaki M, Matsubara M, Hayashi Y, Kangawa K, Sakai T. Ghrelin-producing cells exist as two types of cells, closed- and opened-type cells, in the rat gastrointestinal tract. Peptides 2002; 23 (03) 531-536.
- 27 Schwartz A, Doucet E. Relative changes in resting energy expenditure during weight loss: a systematic review. Obes Rev 2010; 11 (07) 531-547.
- 28 Secher A, Jelsing J, Baquero AF, Hecksher-Sørensen J, Cowley MA, Dalbøge LS. et al. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J Clin Invest 2014; 124 (10) 4473-4488.
- 29 Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A. et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med 2011; 365 (17) 1597-1604.
- 30 Tilg H, Moschen AR. Role of adiponectin and PBEF/visfatin as regulators of inflammation: involvement in obesity-associated diseases. Clin Sci (Lond) 2008; 114 (04) 275-288.
- 31 Wadden TA. Treatment of obesity by moderate and severe caloric restriction. Results of clinical research trials. Ann Intern Med 1993; 119 7 Pt 2 688-693.
- 32 Woods SC, Seeley RJ. Understanding the physiology of obesity: review of recent developments in obesity research. Int J Obes Relat Metab Disord 2002; 26 (Suppl. 04) S8-S10.
- 33 World Health Organization, WHO Fact Sheet. Obesity and overweight; Updated June 2016. Verfügbar unter: http://www.who.int/mediacentre/factsheets/fs311/en/ [letzter Zugriff am 7.11.2016].
- 34 World Health Organization. Obesity: Preventing and Managing the Global Epidemic. World Health Organization; Geneva, Switzerland; 1998
- 35 Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. J Endocrinol 2005; 184 (02) 291-318.
- 36 Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372 6505 425-432.