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Obesity and genetics

Obesity is defined as an abnormal or excessive accumulation of fat that can be detrimental to health (1). Therefore, some of the main questions revolving around it concern whether obesity is genetic or hereditary.

Among the different existing methods to measure and classify 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 and are reflected 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 obesity involves a change in the characteristics of adipose tissue 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 that results in increased circulating concentrations of cholesterol and triglycerides in the blood, being one of the main risk factors for developing ischemic heart disease (4, 5).

 

 Obesity in numbers

According to WHO data, obesity has almost tripled worldwide since 1975. Moreover, according to their most recent estimates, in 2016, more than 650 million adults aged 18 years or older had obesity, which corresponded to 13% of the world’s population within that age range.  

The majority of the world’s population live in countries where overweight and obesity claim more people’s lives than underweight, which is how BMI below what is established as healthy is defined.

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

As an illustrative example of the increase in obesity in developed countries, we show a graph extracted from a study conducted in the U.S. population, 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).

genetic obesity

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)

Risks associated with obesity

Patients with obesity are at high risk of developing a number of conditions that can significantly affect their daily lives, in addition to increasing 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 gastroesophageal reflux disease, functional dyspepsia, irritable bowel syndrome, diverticulosis, inflammatory bowel disease, pancreatitis, and gastrointestinal cancer. Furthermore, obesity can negatively influence the response to specific treatment for gastrointestinal disorders (7).
  • Type 2 diabetes, especially when obesity occurs in childhood and adolescence, increasing the risk of developing type 2 diabetes in youth and young adults (8).
  • Musculoskeletal disorders. The impact will depend on the degree of obesity. The main problem is the weight it puts on the musculoskeletal system over time, resulting mainly in bone and muscle deformation and weakening (3). Among the possible derived affections, we can find osteoarthritis, lumbalgia, osteoporosis and rheumatoid arthritis (9).
  • Respiratory problems, by causing changes in the functinoning of the lungs and chest wall, changes that in turn cause asthma and asthma-like symptoms, such as dyspnea or wheezing (10).
  • Psychological problems. In particular, there’s 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 connecting 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 patients with cancer often 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 observed that people with obesity have an increased risk of severe COVID-19 and death from it (14).

Causes

Obesity is a multifactorial disease, which may 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 beverages 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).
  • Regarding the relationship between genetics and obesity, it’s been proven that several syndromes of genetic origin are associated with the development of obesity. Among them we can find Prader-Willi syndrome and Bardet-Bield syndrome (17,18). 
  • There are also some noteworthy endocrine disorders: 
    • Hypothyroidism, although a causal relationship may be controversial, since, although it’s clear that hypothyroidism is associated with weight gain, in recent years studies indicate 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).

– And finally, obesity can be caused by side effects of some medications, such as corticosteroids, antihypertensives, antihyperglycemics or antidepressants (20).

 

Risk factors

Risk factors associated with obesity can be non-genetic or environmental, such as physical inactivity, age, poor eating habits or even lack of sleep; and genetic, mainly given by certain genetic mutations occurring in genes related to metabolism (21, 22). 

There is an increasing amount of evidence linking gene-environment interactions with this pathology, thus confirming the gene-obesity relationship. Many studies have revealed an influence of genetic factors of between 40 and 70% in changes in BMI (23). In addition, there are several dietary intervention studies that demonstrate the relationship between the metabolic response to low-calorie diets and various 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 taking into account the genetic predispositions of individuals.

Prevention

Most cases of obesity and related conditions can be prevented. WHO recommendations in this area are: 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 and obesity

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 into account these particularities. 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, it is necessary to plan it intelligently, based on the knowledge of our capabilities and limitations. The 24Genetics sports genetic test provides information on cardiovascular, metabolic and muscular profiles and the risk of suffering injuries. This information, together with the advice of a professional, can help you define an optimal sports routine.

 

Bibliography

  1. Obesity and overweight [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 infertility [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 long-term sustainable 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 the 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 diseases. 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. Biología molecular hormonal e investigación clínica [Internet]. 2015 Ago 1 [citado 2022 Feb 21];23(2):47-57. Disponible en: 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? Inmunidad y envejecimiento. 1 de diciembre de 2021;18(1). 
  15. Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalencia de obesidad y obesidad severa entre adultos: Estados Unidos, 2017-2018 Hallazgos clave Datos de la Encuesta Nacional de Examen de Salud y Nutrición. 2017 [citado 2022 Feb 21]; Disponible en: https://www.cdc.gov/nchs/products/index.htm.
  16. Sobrepeso y obesidad | NHLBI, NIH [Internet]. [citado 2022 Feb 18]. Disponible en: https://www.nhlbi.nih.gov/health-topics/overweight-and-obesity
  17. Forsythe E, Beales PL. Bardet-Biedl syndrome. Revista europea de genética humana : EJHG [Internet]. 2013 Jan [citado 2022 Feb 18];21(1):8-13. Disponible en: https://pubmed.ncbi.nlm.nih.gov/22713813/
  18. Tan Q, Orsso CE, Deehan EC, Triador L, Field CJ, Tun HM, et al. Terapias actuales y emergentes para el manejo de la hiperfagia y la obesidad en el síndrome de Prader-Willi: A narrative review. Revisiones de obesidad : una revista oficial de la Asociación Internacional para el Estudio de la Obesidad [Internet]. 2020 May 1 [citado 2022 Feb 18];21(5). Disponible en: https://pubmed.ncbi.nlm.nih.gov/31889409/
  19. Sanyal D, Raychaudhuri M. Hypothyroidism and obesity: An intriguing link. Revista india de endocrinología y metabolismo [Internet]. 2016 Jul 1 [citado 2022 Feb 18];20(4):554-7. Disponible en: https://pubmed.ncbi.nlm.nih.gov/27366725/
  20. Wharton S, Raiber L, Serodio KJ, Lee J, Christensen RAG. Medicamentos que causan aumento de peso y alternativas en Canadá: una revisión narrativa. Diabetes, Metabolic Syndrome and Obesity: Objetivos y terapia [Internet]. 2018 [citado 2022 Feb 18];11:427. Disponible en: /pmc/articles/PMC6109660/
  21. Heianza Y, Qi L. Interacción gen-dieta y nutrición de precisión en la obesidad. Revista internacional de ciencias moleculares [Internet]. 2017 Abr 7 [citado 2022 Feb 18];18(4). Disponible en: https://pubmed.ncbi.nlm.nih.gov/28387720/
  22. Hanson JA, Huecker MR. Privación del sueño. StatPearls [Internet]. 2022 [citado 2022 Feb 18]; Disponible en: 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 [citado 2022 Feb 21];41(1):25. Disponible en: /pmc/articles/PMC2695662/

Written by Debora Pino García

Geneticist

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