Obesity, calories, weight control and chronic disease

Last update: 11 July 2020

This page is a brief summary of what is known – or at least has strongly supported hypotheses to its name – about the relation of food intake, body composition and pathological states. If you believe I missed something important, please send it to me – contact details are on the About Me page. Better sources are always welcome, too.


Caloric management (colloquially “eat less, move more”) is effective for weight gain1 and weight loss2. In a metabolic ward, a “calorie is a calorie”19. However, outside of clinically controlled conditions, it is ineffective for maintenance of weight loss3,24,27, despite being the recommended method of losing weight4 and the most common22.

Significant deviations from a person’s typical weight (both up and down) lead to “metabolic adaptation” or “adaptive thermogenesis”, which reduces caloric expenditure (if weight is lowered) or increases it (if weight is increased)5.

Weight regulation

Humans, similarly to other adipose-bearing animals, have a subconscious, hormone-based fatness regulation system6. This system detects if the individual is too thin or too fat, and regulates basal metabolic rate, hunger and interest in food, through a negative feedback loop mechanism. If body fatness is “too low”, BMR is decreased, while hunger and interest in food is increased25. If body fatness is “too high”, BMR is increased, while hunger and interest in food are decreased. In some people, significant changes in non-exercise physical activity also occur18.

This system works in both lean and obese people7 (except rare cases where it is completely broken8). However, obese people regulate towards a higher “set point”. Where the set point is located is influenced both by food environment9,20,23 and the genetic makeup10 of the individual. Consciously administered physical activity helps little to lower it, unless the level of activity is unusually high26.

It is not clear why the set point drifts up as a person ages.


Typical progression of diabetes. This is a concept graph, axes deliberately unlabeled.

Diabetes (type 2) can be understood as excess energy poisoning21 – the body contains more energy than it can safely store in as trigliceride in the adipose tissue and as glycogen in the liver and muscle tissue, and it spills into places where it shouldn’t be11. This excess, as measured by the body’s ability to quickly store extra energy inputs, is extremely strongly associated with degenerative chronic diseases12,13.

An individual who has exceeded their ability to store more energy, or their “personal fat threshold”14, becomes diabetic. Said individual does not have to be visibly obese, yet they are still too fat to be healthy15. This can be resolved by weight loss by any method16.

Conversely, there exist people who can remain metabolically healthy17, while being obese – they have not exceeded their storage capacity, even though they are visibly obese.


  1. Leaf A, Antonio J. The Effects of Overfeeding on Body Composition: The Role of Macronutrient Composition – A Narrative Review. Int J Exerc Sci. 2017;10(8):1275–1296. Published 2017 Dec 1.
  2. Cioffi I, Evangelista A, Ponzo V, et al. Intermittent versus continuous energy restriction on weight loss and cardiometabolic outcomes: a systematic review and meta-analysis of randomized controlled trials. J Transl Med. 2018;16(1):371. Published 2018 Dec 24. doi:10.1186/s12967-018-1748-4
  3. Fildes A, Charlton J, Rudisill C, Littlejohns P, Prevost AT, Gulliford MC. Probability of an Obese Person Attaining Normal Body Weight: Cohort Study Using Electronic Health Records. Am J Public Health. 2015;105(9):e54–e59. doi:10.2105/AJPH.2015.302773
  4. Guth E. Healthy Weight Loss. JAMA. 2014;312(9):974. doi:10.1001/jama.2014.10929
  5. Rosenbaum M, Leibel RL. Adaptive thermogenesis in humans. Int J Obes (Lond). 2010;34 Suppl 1(0 1):S47–S55. doi:10.1038/ijo.2010.184
  6. Rosenbaum M, Leibel RL. 20 years of leptin: role of leptin in energy homeostasis in humans. J Endocrinol. 2014;223(1):T83–T96. doi:10.1530/JOE-14-0358
  7. Changes in Energy Expenditure Resulting from Altered Body Weight. Rudolph L. Leibel, M.D., Michael Rosenbaum, M.D., and Jules Hirsch, M.D. March 9, 1995, N Engl J Med 1995; 332:621-628, DOI: 10.1056/NEJM199503093321001
  8. I. Sadaf Farooqi, Stephen O’Rahilly, Genetics of Obesity in Humans, Endocrine Reviews, Volume 27, Issue 7, 1 December 2006, Pages 710–718, https://doi.org/10.1210/er.2006-0040
  9. Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake.Kevin D. Hall 5, Alexis Ayuketah, Robert Brychta, Hongyi Cai, Thomas Cassimatis, Kong Y. Chen, Stephanie T. Chung, Elise Costa, Amber Courville, Valerie Darcey, Laura A. Fletcher, Ciaran G. Forde, Ahmed M. Gharib, Juen Guo, Rebecca Howard, Paule V. Joseph, Suzanne McGehee, Ronald Ouwerkerk, Klaudia Raisinger, Irene Rozga, Michael Stagliano, Mary Walter, Peter J. Walter, Shanna Yang, Megan Zhou. Published: May 16, 2019 DOI: https://doi.org/10.1016/j.cmet.2019.05.008
  10. Variability in the heritability of body mass index: a systematic review and meta-regression. Cathy E. Elks1, Marcel den Hoed1, Jing Hua Zhao1, Stephen J. Sharp1, Nicholas J. Wareham1, Ruth J. F. Loos1 and Ken K. Ong1,2*. Front. Endocrinol., 28 February 2012 | https://doi.org/10.3389/fendo.2012.00029
  11. Sattar N, Gill JM. Type 2 diabetes as a disease of ectopic fat?. BMC Med. 2014;12:123. Published 2014 Aug 26. doi:10.1186/s12916-014-0123-4
  12. Jeannie Yip, Francesco S. Facchini, Gerald M. Reaven, Resistance to Insulin-Mediated Glucose Disposal as a Predictor of Cardiovascular Disease, The Journal of Clinical Endocrinology & Metabolism, Volume 83, Issue 8, 1 August 1998, Pages 2773–2776, https://doi.org/10.1210/jcem.83.8.5005
  13. Francesco S. Facchini, Nancy Hua, Fahim Abbasi, Gerald M. Reaven, Insulin Resistance as a Predictor of Age-Related Diseases, The Journal of Clinical Endocrinology & Metabolism, Volume 86, Issue 8, 1 August 2001, Pages 3574–3578, https://doi.org/10.1210/jcem.86.8.7763
  14. Normal weight individuals who develop Type 2 diabetes: the personal fat threshold. Roy Taylor; Rury R. Holman. Clin Sci (Lond) (2015) 128 (7): 405–410. https://doi.org/10.1042/CS20140553
  15. Chadt A, Scherneck S, Joost HG, et al. Molecular links between Obesity and Diabetes: “Diabesity”. [Updated 2018 Jan 23]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279051/
  16. Uusitupa M, Khan TA, Viguiliouk E, et al. Prevention of Type 2 Diabetes by Lifestyle Changes: A Systematic Review and Meta-Analysis. Nutrients. 2019;11(11):2611. Published 2019 Nov 1. doi:10.3390/nu11112611
  17. Faidon Magkos, Metabolically healthy obesity: what’s in a name?, The American Journal of Clinical Nutrition, Volume 110, Issue 3, September 2019, Pages 533–539, https://doi.org/10.1093/ajcn/nqz133
  18. Non-exercise activity thermogenesis (NEAT). Levine JA1. Best Pract Res Clin Endocrinol Metab. 2002 Dec;16(4):679-702.
  19. Hall KD, Guo J. Obesity Energetics: Body Weight Regulation and the Effects of Diet Composition. Gastroenterology. 2017;152(7):1718–1727.e3. doi:10.1053/j.gastro.2017.01.052
  20. STUDIES IN NORMAL AND OBESE SUBJECTS WITH A MONITORED FOOD DISPENSING DEVICE*. Sami A. Hashim Theodore B. Van Itallie. First published: October 1965. https://doi.org/10.1111/j.1749-6632.1965.tb34828.x
  21. Type 2 Diabetes Etiology and reversibility. Roy Taylor, MD, FRCP. Diabetes Care 2013 Apr; 36(4): 1047-1055. https://doi.org/10.2337/dc12-1805
  22. Serdula MK, Williamson DF, Anda RF, Levy A, Heaton A, Byers T. Weight control practices in adults: results of a multistate telephone survey. Am J Public Health. 1994;84(11):1821‐1824. doi:10.2105/ajph.84.11.1821
  23. Hall, K. D., Guo, J., Courville, A. B., Boring, J., Brychta, R., Chen, K. Y., … Chung, S. T. (2020, May 6). A plant-based, low-fat diet decreases ad libitum energy intake compared to an animal-based, ketogenic diet: An inpatient randomized controlled trial. https://doi.org/10.31232/osf.io/rdjfb
  24. Clinical Psychology Review. Volume 11, Issue 6, 1991, Pages 729-780. Confronting the failure of behavioral and dietary treatments for obesity. David M.GarnerSusan C.Wooley https://doi.org/10.1016/0272-7358(91)90128-H
  25. Leah M. Kalm, Richard D. Semba, They Starved So That Others Be Better Fed: Remembering Ancel Keys and the Minnesota Experiment, The Journal of Nutrition, Volume 135, Issue 6, June 2005, Pages 1347–1352, https://doi.org/10.1093/jn/135.6.1347
  26. Swift DL, Johannsen NM, Lavie CJ, Earnest CP, Church TS. The role of exercise and physical activity in weight loss and maintenance. Prog Cardiovasc Dis. 2014;56(4):441-447. doi:10.1016/j.pcad.2013.09.012
  27. Mann, T., Tomiyama, A., Westling, E., Lew, A., Samuels, B., & Chatman, J. (2007). Medicare’s search for effective obesity treatments: diets are not the answer. The American psychologist, 62(3), 220-233. http://dx.doi.org/10.1037/0003-066x.62.3.220 Retrieved from https://escholarship.org/uc/item/2811g3r3