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Obesity and genetics

What is obesity?

Obesity is defined as an abnormal or excessive accumulation of fat that can be detrimental to health (1). Among the different methods for measuring and classifying obesity, the body mass index (BMI) is the most widely used. BMI is calculated by dividing body weight in kilograms by height in meters squared (kg/m2). Thus, different degrees of obesity are established as shown in the following table (2):

 

 

Grade 1 BMI between 30 and 35 kg/m².
Grade 2 (Severe obesity) BMI between 35 and 40 kg/m²
Grade 3 (Morbid obesity) BMI over 40 kg/m².

 

 

In adults, the World Health Organization (WHO) identifies people with a BMI greater than or equal to 30 as obese (1). Progression to the state of obesity involves a change in adipose tissue characteristics and the development of chronic low-grade inflammation. This state is characterized by increased levels of free fatty acids in the circulatory system, pro-inflammatory factors, and activation and infiltration of immune cells at sites of inflammation (3). In addition, obesity is often accompanied by a specific dyslipidemia profile, which is defined as a metabolic abnormality leading to increased circulating concentrations of cholesterol and triglycerides in the blood, being one of the main risk factors for the development of ischemic heart disease (4, 5).

 

Risks associated with obesity

Patients with obesity are at high risk of developing a number of conditions that can significantly affect their daily lives as well as increase mortality risks (3), including the following: 

  • Cardiovascular diseases, such as coronary heart disease, heart failure, hypertension, stroke, atrial fibrillation, and sudden cardiac death (6).
  • Gastrointestinal disorders, including gastro-esophageal reflux disease, functional dyspepsia, irritable bowel syndrome, diverticulosis, inflammatory bowel disease, pancreatitis and gastrointestinal cancer. In addition, obesity may negatively influence the response to specific treatment for gastrointestinal disorders (7).
  • Type 2 diabetes, especially when obesity occurs in childhood and adolescence, increases the risk of developing type 2 diabetes in youth and young adults (8).
  • Musculoskeletal disorders. The impact will depend on the degree of obesity present. The main problem in this regard lies in the burden on the musculoskeletal system over time, mainly resulting in bone and muscle deformation and weakening (3). Possible conditions include osteoarthritis, low back pain, osteoporosis, and rheumatoid arthritis (9).
  • Respiratory problems, cause changes in the mechanics of the lungs and chest wall, which in turn cause asthma and asthma-like symptoms such as dyspnea or wheezing (10).
  • Psychological problems. In particular, there is a reciprocal relationship between depression and obesity. Obesity increases the risk of depression and depression may predict the development of obesity (11). In addition, there are numerous pathways linking stress and obesity (12).
  • Cancer. Obesity is a risk factor for several types of cancer, including breast, colon, endometrial, ovarian, pancreatic, liver, and gastric cancer. Obese cancer patients tend to have a worse prognosis, a poorer response to standard treatments, and are more likely to develop metastatic disease than people of normal weight (13).
  • COVID-19. Multiple scientific studies have found that people with obesity have an increased risk of severe COVID-19 and of dying from it (14).

Obesity in figures

According to WHO data, obesity has almost tripled worldwide since 1975. Moreover, according to its latest estimates, in 2016, more than 650 million adults aged 18 and over were obese, corresponding to 13% of the world’s population in that age range.  

The majority of the world’s population lives in countries where overweight and obesity claim more lives than underweight, as defined by a BMI below what is considered healthy.

As for childhood obesity, in 2016, the WHO reports that 41 million children under the age of five were overweight or obese. In the same year, more than 340 million children and adolescents (aged 5-19 years) were overweight or obese (1).

As an illustrative example of the increase in obesity in developed countries, we show a graph from a study conducted in the US population (Figure 1), where, from 1999-2000 to 2017-2018, the prevalence of obesity increased from 30.5% to 42.4%, and the prevalence of severe obesity increased from 4.7% to 9.2% (15).

 

Figure 1. Trends in age-adjusted obesity and prevalence of severe obesity among adults aged 20 years and older: United States, 1999-2000 to 2017-2018. (15)

 

Causes

Obesity is a multifactorial disease, which can be caused by an energy imbalance, some genetic or endocrine medical conditions, or certain medications. 

  • An energy imbalance means that the amount of calories (energy) obtained from food and drink is different from the amount of calories the body uses. When more calories are taken in than are used, the body stores fat, which eventually leads to the development of obesity (16).
  • In terms of genetic medical conditions, several syndromes of genetic origin have been found to be associated with the development of obesity. These include Prader-Willi syndrome and Bardet-Bield syndrome (17,18). 
  • With regard to endocrine disorders, the following are noteworthy: 
    • Hypothyroidism, although a causal relationship may be controversial, since, although it is clear that hypothyroidism is associated with weight gain, in recent years studies have been carried out indicating that changes in thyroid-stimulating hormone could be secondary to obesity (19).
    • Cushing’s syndrome, a disorder caused by a hormonal imbalance characterized primarily by an excess of cortisol (16).
    • Some tumors, such as craniopharyngioma, which can lead to severe obesity by developing near parts of the brain that control hunger (16).
  • Finally, obesity can be caused by side effects of certain medications, such as corticosteroids, antihypertensives, antihyperglycemics, or antidepressants (20

Risk factors

Risk factors associated with obesity may be non-genetic or environmental, such as physical inactivity, age, poor dietary habits, or even lack of sleep; and genetic, mainly given by certain genetic mutations occurring in genes related to metabolism (21, 22). There is a growing body of evidence linking gene-environment interactions with obesity. A multitude of studies have revealed a 40-70% influence of genetic factors on changes in BMI (23). In addition, there are several dietary intervention studies that demonstrate the relationship between metabolic response to low-calorie diets and several genetic variants, especially those related to obesity, type 2 diabetes, metabolism, and food preferences. The results obtained in these studies tend to support precision dietary interventions considering the genetic predispositions of individuals.

 

Prevention

Most cases of obesity and related conditions are preventable. WHO recommendations in this area are as follows: limit energy intake from fat and sugars; increase consumption of fruits, vegetables, legumes, whole grains, and nuts; and engage in regular physical activity (1). Beyond these recommendations, prevention measures may vary greatly depending on the degree of obesity, predisposition, and causes of obesity, especially in cases where the cause is genetic.

 

24Genetics y obesidad

When it comes to a balanced diet, it is of great importance to take into account the particularities of each person. Nutrigenetics, defined as the discipline that studies the response to nutrition according to each genotype, is essential to take these particularities into account. With the 24Genetics nutrigenetic test, it is possible to study, for each person, the predisposition to lose weight, the greater or lesser effectiveness of various types of diet, and other factors related to food, such as tendencies to emotional eating, snacking, or consumption of sweets, among many other data. 

In addition, sport is the other fundamental factor in preventing and combating obesity. In order to get the most out of training sessions, it is necessary to plan them intelligently, based on the knowledge of our capabilities and limitations. The 24Genetics sports test provides information on cardiovascular, metabolic and muscular profiles or the risk of suffering injuries. This information, together with the advice of a professional, can help you define an optimal sports routine.

 

Bibliography:

1. Obesidad y sobrepeso [Internet]. [cited 2022 Feb 17]. Available from: https://www.who.int/es/news-room/fact-sheets/detail/obesity-and-overweight

2. Meldrum DR, Morris MA, Gambone JC. Obesity pandemic: causes, consequences, and solutions-but do we have the will? Fertility and sterility [Internet]. 2017 Apr 1 [cited 2022 Feb 18];107(4):833–9. Available from: https://pubmed.ncbi.nlm.nih.gov/28292617/

3. Fruh SM. Obesity: Risk factors, complications, and strategies for sustainable long‐term weight management. Journal of the American Association of Nurse Practitioners [Internet]. 2017 Oct 1 [cited 2022 Feb 17];29(Suppl 1):S3. Available from: /pmc/articles/PMC6088226/

4. Trautwein EA, McKay S. The Role of Specific Components of a Plant-Based Diet in Management of Dyslipidemia and the Impact on Cardiovascular Risk. Nutrients [Internet]. 2020 Sep 1 [cited 2022 Feb 17];12(9):1–21. Available from: /pmc/articles/PMC7551487/

5. Musunuru K. Atherogenic Dyslipidemia: Cardiovascular Risk and Dietary Intervention. Lipids [Internet]. 2010 Oct [cited 2022 Feb 17];45(10):907. Available from: /pmc/articles/PMC2950930/

6. Koliaki C, Liatis S, Kokkinos A. Obesity and cardiovascular disease: revisiting an old relationship. Metabolism: clinical and experimental [Internet]. 2019 Mar 1 [cited 2022 Feb 17];92:98–107. Available from: https://pubmed.ncbi.nlm.nih.gov/30399375/

7. Emerenziani S, Guarino MPL, Asensio LMT, Altomare A, Ribolsi M, Balestrieri P, et al. Role of Overweight and Obesity in Gastrointestinal Disease. Nutrients [Internet]. 2020 Jan 1 [cited 2022 Feb 17];12(1). Available from: /pmc/articles/PMC7019431/

8. la Sala L, Pontiroli AE. Prevention of Diabetes and Cardiovascular Disease in Obesity. International Journal of Molecular Sciences [Internet]. 2020 Nov 1 [cited 2022 Feb 18];21(21):1–17. Available from: /pmc/articles/PMC7663329/

9. Anandacoomarasamy A, Caterson I, Sambrook P, Fransen M, March L. The impact of obesity on the musculoskeletal system. International Journal of Obesity 2008 32:2 [Internet]. 2007 Sep 11 [cited 2022 Feb 22];32(2):211–22. Available from: https://www.nature.com/articles/0803715

10. Dixon AE, Peters U. The effect of obesity on lung function. Expert review of respiratory medicine [Internet]. 2018 Sep 2 [cited 2022 Feb 18];12(9):755–67. Available from: https://pubmed.ncbi.nlm.nih.gov/30056777/

11. Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BWJH, et al. Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Archives of general psychiatry [Internet]. 2010 Mar [cited 2022 Feb 18];67(3):220–9. Available from: https://pubmed.ncbi.nlm.nih.gov/20194822/

12. Tomiyama AJ. Stress and Obesity. Annual review of psychology [Internet]. 2019 Jan 4 [cited 2022 Feb 18];70:703–18. Available from: https://pubmed.ncbi.nlm.nih.gov/29927688/

13. O’Flanagan CH, Bowers LW, Hursting SD. A weighty problem: metabolic perturbations and the obesity-cancer link. Hormone molecular biology and clinical investigation [Internet]. 2015 Aug 1 [cited 2022 Feb 21];23(2):47–57. Available from: https://pubmed.ncbi.nlm.nih.gov/26167982/

14. Mohammad S, Aziz R, al Mahri S, Malik SS, Haji E, Khan AH, et al. Obesity and COVID-19: what makes obese host so vulnerable? Immunity and Ageing. 2021 Dec 1;18(1). 

15. Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of Obesity and Severe Obesity Among Adults: United States, 2017-2018 Key findings Data from the National Health and Nutrition Examination Survey. 2017 [cited 2022 Feb 21]; Available from: https://www.cdc.gov/nchs/products/index.htm.

16. Overweight and Obesity | NHLBI, NIH [Internet]. [cited 2022 Feb 18]. Available from: https://www.nhlbi.nih.gov/health-topics/overweight-and-obesity

17. Forsythe E, Beales PL. Bardet-Biedl syndrome. European journal of human genetics: EJHG [Internet]. 2013 Jan [cited 2022 Feb 18];21(1):8–13. Available from: https://pubmed.ncbi.nlm.nih.gov/22713813/

18. Tan Q, Orsso CE, Deehan EC, Triador L, Field CJ, Tun HM, et al. Current and emerging therapies for managing hyperphagia and obesity in Prader-Willi syndrome: A narrative review. Obesity reviews: an official journal of the International Association for the Study of Obesity [Internet]. 2020 May 1 [cited 2022 Feb 18];21(5). Available from: https://pubmed.ncbi.nlm.nih.gov/31889409/

19. Sanyal D, Raychaudhuri M. Hypothyroidism and obesity: An intriguing link. Indian journal of endocrinology and metabolism [Internet]. 2016 Jul 1 [cited 2022 Feb 18];20(4):554–7. Available from: https://pubmed.ncbi.nlm.nih.gov/27366725/

20. Wharton S, Raiber L, Serodio KJ, Lee J, Christensen RAG. Medications that cause weight gain and alternatives in Canada: a narrative review. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy [Internet]. 2018 [cited 2022 Feb 18];11:427. Available from: /pmc/articles/PMC6109660/

21. Heianza Y, Qi L. Gene-Diet Interaction and Precision Nutrition in Obesity. International journal of molecular sciences [Internet]. 2017 Apr 7 [cited 2022 Feb 18];18(4). Available from: https://pubmed.ncbi.nlm.nih.gov/28387720/

22. Hanson JA, Huecker MR. Sleep Deprivation. StatPearls [Internet]. 2022 [cited 2022 Feb 18]; Available from: https://pubmed.ncbi.nlm.nih.gov/31613456/

23. Willer CJ, Speliotes EK, Loos RJF, Li S, Lindgren CM, Heid IM, et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nature genetics [Internet]. 2009 Jan [cited 2022 Feb 21];41(1):25. Available from: /pmc/articles/PMC2695662/

 

Written by Debora Pino García

Geneticist

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