Introduction
Many Causes of obesity can be stated, and the major role being played by genetics should also be noted. Although obesity can be caused due to stagnant lifestyle, or changes in hormonal balance leading to endocrinal disorders, genetics also are included in the list. The influence of genetics related to eating patterns and exercise was studied, proving its major role.
With urbanization, obesity in children as well as adults has increased, clearly indicating the effect of the environment. But it is also observed that not all individuals are obese in an urbanized environment which points out that the individual variation in fat mass and weight, which is influenced by genetic behavioral and developmental changes, has also occurred. This article will throw light on the genetics which causes obesity.
How Do Genes Function in Obesity?
Genetic and epigenetic changes lead to this condition, which influences the body's metabolic pathway functions and balances the neural pathways and centers of appetite (hunger). These alterations can result in differences leading to hypertension (increased blood pressure), hyperlipidemia (increased lipid content), insulin resistance, fat deposition (ectopic) in the liver, and dyslipidemia (unbalanced lipid content) which are the main indicators of obesity.
Genetic mutations can be autosomal recessive or autosomal dominant inheritance. This is influenced by the mechanism of translocation, genetic imprinting, and deletion.
Epigenetic changes include more complex changes and can be passed on from parents or can occur at any time, causing obesity in the individual.
The following are the factors that influence epigenetic changes:
-
Maternal Nutrition: Overnutrition and undernutrition can lead to changes that affect the fetus. Intrauterine retardation of growth and undernutrition are major risk factors for insulin metabolism alteration. Upon providing high nutrition, these children can develop obesity. Type 2 diabetes can also occur due to this.
-
Exposure of the Mother to Toxins: Polycyclic aromatic hydrocarbons, and organochlorides, are toxins that can lead to diabetes mellitus and fetal metabolic syndrome. Smoking cigarettes can also lead to changes epigenetically.
-
Diet-induced obesity is associated with maternal stress.
-
Decreased pre-pregnancy weight or young maternal age are also associated with changes in the fetal metabolism, later leading to obesity.
-
Alteration in the microbial flora of the gut, along with the use of antibiotics in the early phases of life, can lead to obesity or non-alcoholic liver disease.
-
Prediabetes and a decrease in the protein diet have been linked to the changes in epigenetic factors which are associated with obesity in the fetus.
What Are the Issues of Concern in Genetics Linked to Obesity?
Genetic obesity is classified into the following:
Monogenic Obesity:
This denotes a single gene nutrition that is located in the leptin-melanocortin pathway.
Monogenic obesity can be divided into:
-
Autosomal Recessive Inheritance: Mutations in leptin receptors occur, leading to frame-shift or nonsense mutations that cannot be treated. Other mutations occurring in POMC (propiomelanocortin) can be treated.
-
Autosomal Dominant Inheritance: Mutations in gene SH2B1 present on the 16th chromosome are also an autosomal dominant inheritance. These mutations give rise to proteins that are involved in the development of obesity. NPU gene mutations, FTO gene mutations, and MC3R gene mutations are other alterations in the gene that can also contribute to obesity.
Lipton signaling pathway alterations are the main cause of obesity. This pathway includes a series of reactions that show the effect on the hypothalamus to create a feeling of satiety (satisfaction).
Polygenic Obesity:
-
A large number of cumulative genes that affect obesity are called polygenetic obesity.
-
Polygenic obesity is 60% of all obesities and involves mutations of the gene, which help in uncoupling proteins of skeletal adipose tissue. The effect on the utilization of energy and lipolysis (breakdown of lipids) is also due to a change in the gene. These, in turn, affect the control of appetite and, subsequently, the energy balance.
-
Epigenetic modifications:
-
Methylation of the DNA (deoxyribonucleic acid).
-
Modification of the cysteamine by a process of acetylation along with methylation.
-
Variation in the body mass index due to certain genes.
Syndromic Obesity:
-
It is classified as obesity caused due to chromosomal rearrangements and pleiotropic syndromes.
-
Prader-Willy syndrome is due to a mutation in the paternal gene, characterized by short stature, hypotonia (decrease in muscle tone), retardation mentally, abnormal faces, hormonal deficiency, and obesity.
-
Clear traffic syndrome causes type 2 diabetes, dyslexia (learning disorder), obesity, renal abnormalities, polydactyly (fingers more than normal), and also decreased learning efficiency.
What Is the Clinical Significance of Genetics Linked to Obesity?
-
Causes of obesity linked to genetics should involve taking proper history and clinical examination.
-
Proper history includes family history, personal history, exercise and diet history, medication history, psychosocial history, along with weight gain history.
-
Obesity can also be caused due to hypothyroidism, hypothalamic obesity, and Cushing's disease must be ruled out.
-
Syndromic obesity can be identified on the basis of the clinical features of the syndrome.
-
Laboratory investigations are carried out to find out any abnormalities. Once all the lab investigations are normal, genetic testing is carried out.
-
Genetic testing includes analysis of linkage to look for variability.
-
Benefits for patients with obesity can be gained by surgeries like bariatric surgery, laparoscopic gastric banding, and sleeve gastrectomy that help in weight loss.
How to Enhance Healthcare Team Outcomes?
-
It is well understood that the important role is played by genetics and epigenetics in obesity. Dedicated healthcare professionals are required for diagnosing, managing, and also supporting patients. Healthcare professionals from various fields are required to produce good teamwork. Obstetricians, nutritionists, pediatricians, psychologists, and geneticists work together to mitigate risk factors that are associated with childhood and maternal obesity.
-
Childhood obesity diagnosis can be done with the help of a pediatric endocrinologist. Adult endocrinologist deal with diabetes and other parameters which cause epigenetic changes passed from the parents. Bariatric surgery, lifestyle modifications, and medications are the basic treatments for obesity linked with genetics.
Conclusion
Studies were carried out highlighting the regulation of body weight by the brain and have also covered the role of certain signals in pathways and genetic causes leading to obesity. Environmental and genetic factors influence the development of obesity in individuals. Considering the causes like genetics and epigenetics and understanding the role played by genetic changes which influence obesity will help the health care physician in managing obesity efficiently.
