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The interactions between obesity, metabolism and the brain

Appetite regulation

Obesity occurs when there is an imbalance between energy intake and energy expenditure, and our brains are at centre of it. Under normal circumstances, long term energy balance is centrally regulated by the brain receiving peripheral input.1-3 The imbalance in energy intake and expenditure can result from changes in these peripheral signals, as well as other factors such as genetic predisposition and the impact of medications. 1-3

Environmental, societal and psychological factors – together with the pleasure we derive from food (hedonic factors) – can also influence energy balance, which in turn can lead to weight gain. 1 Once established, powerful neuro-hormonal factors effectively defend the body against weight loss, thereby often making obesity a lifelong problem, where weight regain (or relapse) is the rule, rather than the exception. 1

Infographic showing regulation of energy balance.

Metabolic adaptations to weight loss

Our bodies are programmed to respond to weight loss with weight regain.1,4-7 Weight loss alters the body's homeostatic system,8 which controls appetite, energy intake and energy expenditure,9 causing the body to increase hunger and lower the metabolic rate8 – this process is known as metabolic adaptation.

Maintaining weight loss is challenging

A review of 14 long-term studies showed that people with obesity regained weight after weight loss achieved by dieting.10

Infographic showing mean weight change of diets.
Visual adapted from 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;622(3):220–233.

“…the high rate of relapse among people with obesity who have lost weight has a strong physiological basis and is not simply the result of the voluntary resumption of old habits.”10

Furthermore, the ACTION IO study* found that 81% of people with obesity have engaged in one or more serious weight loss attempts; however, only 11% were able to maintain a 5% weight loss for one year or more. 11

Maintaining weight loss is challenging for people living with obesity, and these findings show that obesity isn’t about willpower. Therefore for many people, medical intervention may be needed to manage weight.

*The Awareness, Care and Treatment in Obesity MaNagement – an International Observation (ACTION IO) Study is the first international study to investigate barriers to obesity management among people with obesity and healthcare professionals in 11 countries worldwide (Australia, Chile, Israel, Italy, Japan, Mexico, Saudi Arabia, South Korea, Spain, UAE, UK). A total of 14,502 people with obesity and 2,785 healthcare professionals completed the survey.11


  1. Gadde et al. Obesity: Pathophysiology and Management. J Am Coll Cardiol. 2018;71:69–84

  2. Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011; 365:1597–1604.

  3. Heymsfield and Wadden. Mechanisms, Pathophysiology, and Management of Obesity. N Engl J Med. 2017;376:1492.

  4. Schwartz A and Doucet E. Relative changes in resting energy expenditure during weight loss: a systematic review. Obes Rev. 2010; 11:531–547.

  5. Sumithran P and J P. The defence of body weight: a physiological basis for weight regain after weight loss. Clin Sci (Lond). 2013; 124:231–241.

  6. Rosenbaum M and RL L. Adaptive thermogenesis in humans. Int J Obes (Lond). 2010; 34 (suppl 1):S47–S55.

  7. Rosenbaum M, Kissileff HR, Mayer LE, et al. Energy intake in weight-reduced humans. Brain Res. 2010; 1350:95-102.

  8. Greenway F. Physiological adaptations to weight loss and factors favouring weight regain. International Journal of Obesity. 2015; 39:1188-1196.

  9. Lenard N and Berthoud H. Central and Peripheral Regulation of Food Intake and Physical Activity: Pathways and Genes. Obesity. 2008; 16(Suppl 3):S11-S12.

  10. Mann T, Tomiyama AJ, Westling E, et al. Medicare's search for effective obesity treatments: diets are not the answer. Am Psychol. 2007; 62:220-233.

  11. Caterson ID, Alfadda AA, Auerbach P, et al. Gaps to bridge: Misalignment between perception, reality and actions in obesity. Diabetes Obes Metab. 2019; 21:1914-1924

HQ21OB00062, Approval date: April 2021

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