Genetics and metabolism: how heredity affects weight

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Genetics and metabolism: how heredity affects weight

I. Fundamentals of genetics and metabolism

  1. Genetics: Life Drawing

    a. DNA: Molecule of heredity: DNA (deoxyribonucleic acid) is the main carrier of genetic information. Its structure, a double spiral, contains a sequence of nucleotides (adenin, thyme, cytosine and guanine), which encode instructions for protein synthesis. These proteins perform a wide range of functions in the body, determining our physical characteristics, predisposition to diseases and metabolic processes.

    b. Genes: units of heredity: Genes are specific areas of DNA containing instructions for the synthesis of certain proteins or functional RNA molecules. Each person inherits two copies of each gene, one from each parent. Variations in the sequence of DNA genes are called alleles.

    c. Chromosomes: organized DNA: DNA is organized in chromosomes, structures located in the core of the cell. A person usually has 23 pairs of chromosomes, 22 pairs of autosomes and one pair of sex chromosomes (XX in women and XY in men).

    d. Genom: a complete set of instructions: The genome is a complete set of the genetic information of the body, including all genes and non -dodging areas of DNA. The study of the genome allows you to identify genetic options associated with various signs, including a predisposition to obesity.

    e. Epigenetics: environmental influence on genes: Epigenetics studies changes in genes expression that are not associated with changes in the sequence of DNA. Epigenetic modifications, such as DNA methylation and histones modifications, can affect genes and, therefore, metabolism and weight. These changes can be caused by environmental factors, such as diet, physical activity and the effects of toxins.

  2. Metabolism: Fuel for life

    a. Definition Metabolism: Metabolism is a combination of all chemical reactions taking place in the body to maintain life. It includes two main processes: anabolism (synthesis of complex molecules made of simple) and catabolism (splitting complex molecules into simple).

    b. The main metabolic pathways:

    i.  **Метаболизм углеводов:** Углеводы расщепляются до глюкозы, которая используется для производства энергии посредством гликолиза, цикла Кребса и окислительного фосфорилирования. Избыток глюкозы может быть преобразован в гликоген (запасная форма глюкозы) или жир.

ii.  **Метаболизм жиров:** Жиры расщепляются до жирных кислот и глицерина. Жирные кислоты могут быть окислены для производства энергии посредством бета-окисления. Жиры также являются важными структурными компонентами клеточных мембран и используются для синтеза гормонов.

iii.  **Метаболизм белков:** Белки расщепляются до аминокислот. Аминокислоты используются для синтеза новых белков, а также могут быть преобразованы в глюкозу или жиры.

    c. Basal metabolism (BMR): BMR is the amount of energy needed by the body at rest to maintain basic functions, such as breathing, blood circulation and maintaining body temperature. BMR depends on many factors, including age, gender, weight, height and genetics.

    d. Metabolism speed: The rate of metabolism is the total speed with which the body burns calories. It includes BMR, the thermal effect of food (energy spent on digestion and absorption of food) and energy spent on physical activity.

    e. Metabolism regulation: Metabolism is regulated by a complex network of hormones, enzymes and signal routes. Hormones, such as insulin, glucagon, thyroid hormones and leptin, play a key role in the regulation of the metabolism of glucose, fats and proteins.

II. Genetic factors affecting weight

  1. Genes associated with appetite and saturation:

    a. Ген FTO (Fat mass and obesity-associated gene): FTO is one of the most studied genes associated with obesity. Options in the FTO gene are associated with an increased risk of obesity, increased calorie consumption and reduced physical activity. It is believed that FTO affects appetite and saturation, possibly by its influence on the hypothalamus, the area of ​​the brain, which is responsible for the regulation of hunger and satiety.

    b. MC4R gene (Melanocortin 4 Receptor Gene): MC4R encodes a melanocortine receptor 4, which plays a key role in the regulation of appetite and energy balance. Mutations in the MC4R gene are the most common form of monogenic obesity. People with mutations in MC4R often experience severe hunger and are prone to overeating.

    c. LEPR gene (Leptin Receptor Gene): LEPR encodes the leptin, hormone receptor produced by fat cells, which signals the brain of saturation. Mutations in the LEPR gene can lead to leptin signal deficiency, which leads to increased appetite and obesity.

    d. Ген POMC (Proopiomelanocortin gene): POMC encodes a precursor protein, which breaks down into several hormones, including alpha-melanocytimulating hormone (Alfa-MSG), which suppresses appetite. Mutations in the POMC gene can lead to alpha-MSG deficiency, which leads to increased appetite and obesity.

    e. ~ Ghrel (Ghrelin Gene): Ghrel encodes Grelin, a hormone produced by the stomach, which stimulates appetite. Variations in the GHREL gene can affect the level of Grelin and, therefore, to appetite.

  2. Genes affecting metabolism:

    a. Гены UCP (Uncoupling protein genes): UCP is encoded by proteins that regulate thermogenesis (heat production) in mitochondria. Variations in the UCP genes can affect the rate of metabolism and, therefore, to a predisposition to obesity. For example, UCP1 (thermogenin) plays a key role in thermogenesis in brown adipose tissue.

    b. Гены PPAR (Peroxisome proliferator-activated receptor genes): PPAR is encoded by nuclear receptors that regulate the metabolism of fats and glucose. Variations in PPar genes can affect the level of lipids in the blood, sensitivity to insulin and a predisposition to obesity.

    c. Гены ADRB (Adrenergic receptor beta genes): Adrb encodes beta-adrenergic receptors that regulate lipolysis (splitting fats) and thermogenesis. Variations in ADRB genes can affect the body’s ability to burn fat and, therefore, to a predisposition to obesity.

    d. Genes KCNJ11 and ABCC8: These genes encode the components of ATP-dependent potassium canal (KATP channel) in pancreatic beta cells. These channels play an important role in the regulation of insulin secretion. Variations in these genes can affect the level of insulin and sensitivity to insulin, which affects glucose metabolism and the risk of type 2 diabetes and obesity.

    e. Lipid metabolism genes: Many genes participate in lipid metabolism, including genes encoding lipoproteinlipase (LPL), apolipoproteins (APOE, APOC3) and enzymes involved in cholesterol synthesis (HMGCR). Variations in these genes can affect the level of lipids in the blood and the risk of developing cardiovascular diseases, as well as a predisposition to obesity.

  3. Genes affecting the distribution of fat:

    a. Ген IRS1 (Insulin receptor substrate 1 gene): IRS1 encodes a protein participating in the transmission of insulin signals. Variations in the IRS1 gene can affect sensitivity to insulin and fat distribution.

    b. Ген LIPE (Lipase E, hormone-sensitive type gene): Lip encodes a hormone-sensitive lipase, an enzyme that breaks down fats in fat cells. Variations in the LIPE gene can affect lipolysis and fat distribution.

    c. GEN GEN1 (PERILIPIN 1 GENE): PLIN1 encodes a protein that covers fat drops in fat cells and regulates lipolysis. Variations in the PLIN1 gene can affect the distribution of fat.

    d. Genes associated with the development of adipose tissue: Genes involved in the development and differentiation of adipocytes (fat cells) can also affect the distribution of fat. These include genes encoding transcription factors, such as PParγ and C/EBPα.

  4. Monogenic obesity:

    a. Determination of monogenic obesity: Monogenic obesity is obesity caused by a mutation in one gene. Although monogenic obesity is relatively rare, the study of these genes revealed important ways of regulating appetite and energy balance.

    b. Examples of genes that cause monogenic obesity:

    i.  **MC4R:** Как упоминалось ранее, мутации в гене MC4R являются наиболее распространенной формой моногенного ожирения.

ii.  **LEP:** Мутации в гене лептина (LEP) приводят к дефициту лептина, что приводит к сильному голоду и ожирению.

iii.  **LEPR:** Мутации в гене рецептора лептина (LEPR) также приводят к дефициту сигнала лептина и ожирению.

iv.  **POMC:** Мутации в гене POMC приводят к дефициту альфа-МСГ и ожирению.

v.  **PCSK1 (Proprotein convertase subtilisin/kexin type 1 gene):** PCSK1 кодирует фермент, который процессирует многие гормоны, включая инсулин и грелин. Мутации в гене PCSK1 могут приводить к ожирению, а также к другим эндокринным нарушениям.

  5. Polygenic obesity:

    a. Determination of polygenic obesity: Polygenic obesity is obesity caused by the interaction of many genes, each of which has a slight influence on weight. Most cases of obesity are polygenic.

    b. Identification of genes associated with polygenic obesity: Studies of associations throughout the genome (GWAS) are used to identify genetic options (single -okleotide polymorphisms or SNP) associated with obese in large populations.

    c. Genetic risks: Genetic risks based on a set of SNP can be used to assess a genetic predisposition to obesity.

III. Interaction of genes and the environment

  1. Genetical and environmental interaction:

    a. Determination of genetically medium interaction: Genetical-environmental interaction occurs when the influence of the genetic variant on the sign (for example, weight) depends on the impact of the environment.

    b. Examples of genetically environmental interaction in relation to weight:

    i.  **FTO и физическая активность:** Влияние гена FTO на вес может быть более выраженным у людей с низкой физической активностью. Физическая активность может компенсировать генетическую предрасположенность к ожирению, связанную с FTO.

ii.  **FTO и диета:** Влияние гена FTO на вес также может зависеть от диеты. Например, влияние FTO может быть более выраженным у людей, употребляющих пищу с высоким содержанием жиров или сахара.

iii.  **MC4R и диета:** Влияние мутаций в гене MC4R на вес может быть уменьшено при помощи строгой диеты и режима физических нагрузок.

    c. Plastity of genes: Genes plasticity refers to the ability of genes in different ways, depending on the impact of the environment.

  2. Epigenetics and weight:

    a. Epigenetic modifications: Epigenetic modifications, such as DNA methylation and histones modifications, can affect the expression of genes associated with metabolism and weight.

    b. Environmental influence on epigenetics: Environmental factors, such as diet, physical activity and the effects of toxins, can cause epigenetic changes that can be transmitted from generation to generation.

    c. Examples of epigenetic changes associated with weight:

    i.  **Внутриутробное питание:** Питание матери во время беременности может влиять на эпигенетические изменения у ребенка, которые могут повлиять на риск ожирения в дальнейшей жизни.

ii.  **Раннее детство:** Питание и воздействие окружающей среды в раннем детстве также могут вызывать эпигенетические изменения, которые влияют на риск ожирения.

iii.  **Диета и метилирование ДНК:** Определенные компоненты диеты, такие как фолиевая кислота и витамин B12, участвуют в метилировании ДНК. Недостаток этих питательных веществ может влиять на метилирование ДНК и, следовательно, на экспрессию генов, связанных с метаболизмом.

  3. The role of intestinal microbioma:

    a. Microbia of the intestines and metabolism: The intestinal microbia, the totality of microorganisms living in the intestine, plays an important role in metabolism and energy balance.

    b. The effect of microbioma by weight: The composition of the intestinal microbioma can affect the absorption of calories, inflammation and sensitivity to insulin, which can affect weight.

    c. Genetics and microbias: Genetic factors can affect the composition of the intestinal microbioma.

    d. Diet and microbioma: The diet also has a strong effect on the composition of the intestinal microbioma.

    e. The influence of microbioma on the expression of genes: Microbia can affect the expression of the owner of the owner through the production of metabolites, such as short -chain fatty acids (KCHK).

IV. Genetic testing and personalized medicine

  1. Genetic testing to assess the risk of obesity:

    a. Types of genetic tests: There are various types of genetic tests that can be used to assess the risk of obesity, including:

    i.  **Тестирование отдельных генов:** Эти тесты оценивают наличие конкретных генетических вариантов, связанных с ожирением, таких как варианты в гене FTO или MC4R.

ii.  **Полигенные рисковые оценки (PRS):** PRS оценивают совокупный эффект множества генетических вариантов на риск ожирения.

iii.  **Геномное секвенирование:** Геномное секвенирование позволяет определить полную последовательность ДНК человека, что может помочь выявить редкие генетические варианты, связанные с ожирением.

    b. Advantages of genetic testing: Genetic testing can help identify people with an increased risk of obesity, which allows them to take preventive measures, such as a change in lifestyle.

    c. Genetic testing restrictions: Genetic testing is not determined. It does not predict that a person will certainly develop obesity, but only indicates an increased risk. In addition, genetic tests do not take into account all factors affecting weight, such as environmental factors.

  2. Personalized diet and physical exercises:

    a. Personalized approach to weight management: Personalized medicine is aimed at developing individual approaches to the prevention and treatment of diseases based on genetic, environmental and exemplary factors.

    b. Genetically oriented dietary recommendations: Genetic testing can be used to develop dietary recommendations adapted to the human genetic profile. For example, people with certain options in the FTO GE can be recommended to eat low fat and sugar content.

    c. Genetically oriented recommendations on physical activity: Genetic testing can also be used to develop recommendations on physical activity adapted to the human genetic profile. For example, people with certain options in ADRB genes can be recommended to engage in aerobic exercises to increase lipolysis.

    d. Prospects for personalized medicine: Personalized medicine has a potential for improving the effectiveness and safety of obesity treatment.

V. Conclusions and future research areas

  1. The complexity of weight genetics: Body weight is a complex sign, which is affected by many genes and environmental factors.

  2. The need for further research: Further studies are needed to identify all the genes related to obesity, and for understanding how genes interact with environmental factors.

  3. Development of new treatment strategies: Understanding the genetic and metabolic foundations of obesity can lead to the development of new treatment strategies aimed at specific genetic and metabolic pathways.

  4. The role of prevention: Prevention of obesity, starting from an early age, is crucial for reducing global burden.

  5. Ethical considerations: It is important to consider ethical considerations associated with genetic testing and personalized medicine, such as confidentiality, discrimination and accessibility.

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