The Science of Obesity

Image adapted from Badman, Flier. Science 2005;307:1909–14; 2. US Department of Health and Human Services, 1998. NIH Publication No. 98-4083

Key scientific aspects of weight management are; energy balance, genetics and epigenetics, hormones and neurotransmitters, environmental factors, gut microbiome and inflammation. Each of these areas play a role in maintaining the metabolism and the healthy weight of an individual. 

Obesity is primarily driven by an imbalance between energy intake (calories consumed) and energy expenditure (calories burned). When energy intake exceeds expenditure over an extended period, it leads to weight gain. While ‘calories in vs calories out’ is outdated and does not tend to hold up in today’s scientific literature, factors such as food quality, processing, chemicals etc. also play a role. Fundamentally if an individual consumes many more calories than they expend they will gain weight. Over time this will lead to fundamental changes to the metabolic system and the disease state, Obesity. See also the Set Point topic.

Genetic factors also play a significant role in determining an individual’s susceptibility to obesity. Certain genetic variations can influence metabolism, fat storage, and the regulation of hunger and appetite. Some genetic tests can determine an individual’s propensity to regain weight after loss and also whether they have the FTO or MC4R gene variations which are associated with Obesity.²  

Epigenetic modifications can influence gene expression related to obesity and metabolic health. Environmental factors can affect epigenetic changes that may increase obesity risk. ⁷

The endocrine system, including hormones like insulin, leptin, and ghrelin, as well as neurotransmitters like dopamine, serotonin, and endocannabinoids, plays a crucial role in regulating appetite, metabolism, and fat storage. As these neurotransmitter and hormone levels can vary throughout life stages (for example menopause, pregnancy, growth phases) so they can effect the functioning of the metabolic system throughout periods of life. ³ 

The environment, including access to unhealthy food, food marketing, and sedentary lifestyles, can contribute to obesity. Socioeconomic, cultural, and built environment factors also play a role. ⁴

Emerging research has highlighted the role of the gut microbiota in obesity. Programs such as Zoe, have highlighted to consumers that the composition of gut bacteria can affect digestion, nutrient absorption, and metabolism and therefore weight gain and loss. ⁵

Chronic low-grade inflammation is associated with obesity and can contribute to insulin resistance and other metabolic disturbances.  ⁶ Chronic inflammation is a continuing area of research not only for weight management but also for cellular ageing. 

Understanding the science behind obesity and overweight is crucial for developing effective prevention and treatment strategies. It’s a multidisciplinary field that integrates knowledge from genetics, nutrition, physiology, endocrinology, and environmental science. 

References:

1. • Hill, J. O., Wyatt, H. R., & Peters, J. C. (2012). Energy balance and obesity. Circulation, 126(1), 126-132.

• • Loos, R. J. (2018). Genetic determinants of common obesity and their value in prediction. Best Practice & Research Clinical Endocrinology & Metabolism, 32(2), 139-146.

• • Berthoud, H. R., Münzberg, H., & Morrison, C. D. (2017). Blaming the brain for obesity: Integration of hedonic and homeostatic mechanisms. Gastroenterology, 152(7), 1728-1738.

• • Swinburn, B. A., Sacks, G., Hall, K. D., McPherson, K., Finegood, D. T., Moodie, M. L., & Gortmaker, S. L. (2011). The global obesity pandemic: Shaped by global drivers and local environments. The Lancet, 378(9793), 804-814.

• • Tremaroli, V., & Bäckhed, F. (2012). Functional interactions between the gut microbiota and host metabolism. Nature, 489(7415), 242-249.

• • Hotamisligil, G. S. (2006). Inflammation and metabolic disorders. Nature, 444(7121), 860-867.

• • Ling, C., Rönn, T. (2019). Epigenetics in human obesity and type 2 diabetes. Cell Metabolism, 29(5), 1028-1044.