Overweight (Obesity): Causes

Pathogenesis (development of disease)

The cause of obesity is an imbalance between energy intake and energy expenditure. The result is a positive energy balance and means weight gain. This results in an increase in depot fat (subcutaneous and visceral). There is also an increase in so-called ectopic fat (fat that occurs in places that are not typical for it) – especially in the liver, muscles and pancreas (pancreas). In addition to the above-mentioned factor, there may be a genetic predisposition to obesity, which, together with various environmental factors, can lead to obesity. In addition, increased resistin and decreased adiponectin levels are characteristic. Both are mediators (“mediators”) from the adipose tissue. Reduced formation of satiety hormones in the stomach and intestines could also be responsible for obesity, with the consequence that the feeling of satiety occurs later. The satiety hormones are produced by mucosal cells in the stomach and intestine (= entero-endocrine (formerly entero-chromaffin) cells). The I cells release cholecystokinin (CCK), and L cells produce peptide YY (PYY) or glucagon-like peptides 1 and 2 (GLP-1, GLP-2). The X/A cells of the stomach produce the hormone ghrelin (acronym, Growth Hormone Release Inducing). Ghrelin, together with the hormones leptin and cortisol, regulates the sensation of hunger and satiety.The reduced formation of satiety hormones in the stomach and intestine has now been confirmed by laboratory tests: obese patients had reduced concentrations of CCK, GLP-1, PYY, and especially ghrelin in the blood after a meal.

Etiology (Causes)

Biographic Causes

  • Genetic burden – obesity; type 2 diabetes mellitus (especially in first-degree relatives); other genetic causes:
    • Genetic risk dependent on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
        • Genes: FTO, MC4R
        • SNP: rs1121980 in the gene FTO
          • Allele constellation: CT (1.67-fold).
          • Allele constellation: TT (2.76-fold)
        • SNP: rs10871777 in the gene MC4R
          • Allele constellation: AG (1.22-fold).
          • Allele constellation: GG (1.5-fold)
      • Gene variant: point mutation in the FTO gene; promotes the development of white fat cells in the body, which, unlike brown fat cells, store fat instead of turning it into heat
    • Genetic diseases
      • Beta-3 receptor defect – genetic disorder with unclear inheritance; the β3-adrenoceptor is found predominantly in brown adipose tissue, where it leads to lipolysis (fat cleavage) and thermogenesis (heat production).
      • Klinefelter syndrome – genetic disease with mostly sporadic inheritance: numerical chromosomal aberration (aneuploidy) of the sex chromosomes (gonosomal abnormality), which occurs only in boys or Men occurs; in the majority of cases characterized by a supernumerary X chromosome (47, XXY); clinical picture: large stature and testicular hypoplasia (small testis), caused by hypogonadotropic hypogonadism (gonadal hypofunction); usually spontaneous onset of puberty, but poor pubertal progress.
      • Laurence-Moon-Biedl-Bardet syndrome (LMBBS) – rare genetic disorder with autosomal recessive inheritance; according to clinical symptoms is differentiated into:
        • Laurence-Moon syndrome (without polydactyly, i.e., without the appearance of supernumerary fingers or toes, and obesity, but with paraplegia (paraplegia) and muscle hypotonia/reduced muscle tone) and
        • Bardet-Biedl syndrome (with polydactyly, obesity and peculiarities of the kidneys).
      • Leptin resistance – genetic disease with autosomal recessive inheritance; leptin inhibits the occurrence of hunger pangs, in the case of leptin resistance, the physiological effect of leptin on the target neurons fails – the appetite suppressant effect thus does not occur.
      • Prader-Willi syndrome (PWS; synonyms: Prader-Labhard-Willi-Fanconi syndrome, Urban syndrome, and Urban-Rogers-Meyer syndrome) – genetic disorder with autosomal dominant inheritance occurring in approximately 1 in 10,000 to 1 in 20,000 births; characteristic features include. Among other things, a pronounced overweight in the absence of a sense of satiety, short stature and intelligence reduction; in the course of life, diseases such as diabetes mellitus type 2 occur due to obesity.
      • Stewart-Morel-Morgagni syndrome (Morgagni-Stewart syndrome) – genetic disorder with autosomal-dominant or X-linked recessive inheritance associated with frontal hyperostosis (thickening of the internal plate of the frontal bone) and possibly associated with obesity (overweight) and virilization (masculinization, i.e. expression of male sexual characteristics or a male phenotype in a genetically female individual); affected are predominantly females.
  • Diseases of the mother
    • Overweight or obesity
      • Obesity in pregnant women is associated with increased fetal growth; this was detectable from 21 weeks’ gestation and was associated with significantly increased birth weight (100 g heavier; mean 3,373 g versus 3,279 g).CONCLUSION: It is possible that fetal programming may lead to obesity later in life.
      • Children of overweight or obese mothers born vaginally were three times more likely to be overweight at 3 years of age (odds ratio of 3.07, 95% confidence interval:1.58-5.96); after caesarean section, the risk was even more than fivefold increased (odds ratio 5.55; 2.55-12.04). The authors were able to demonstrate a specific influence on the intestinal flora of the children for the type of delivery in each case.
    • Diabetes mellitus type 1
      • Risk of obesity and insulin resistance is significantly increased in children of mothers with type 1 diabetes.
  • Age
    • Puberty – less calorie consumption at rest than expected by increasing growth.
    • In both men and women, as well as in children and adolescents, BMI (body mass index/body mass index) increases with age
  • Social factors – Living alone, not married and socially inactive (no social network).
  • Socio-cultural factors – People who grew up in an environment of low education or low social status have a higher risk of obesity. Among these, the proportion of children adolescents from migrant families, especially those who come from Turkey, Poland, Central and Southern Europe is higher.
  • Overweight at birth (macrosomia: > 4,000 g) → doubling the risk of becoming overweight later in life.
  • Children who were not breastfed also have a higher risk of disease
  • Hormonal factors – gravidity (pregnancy), menopause (menopause).

Behavioral causes

  • Nutrition
    • Chronic overeating
      • High caloric intake ↑↑
      • High fat diet (1 g of fat provides 9.3 kcal); this results in stimulation of leptin and insulin secretion. This results in initial stimulation of beta receptors, but then down-regulation occurs, so that compensatory activation of the sympathetic nervous system – an energy expenditure increasing mechanism – is absent
        • High proportion of saturated fatty acids (↑).
        • High proportion of monounsaturated fatty acids (↑)
        • High proportion of polyunsaturated fatty acids ?
      • High sugar consumption, esp. mono- and disaccharides (monosaccharides and polysaccharides), due to excessive consumption of sweets and sweet drinks; with excessive intake of carbohydrates and amino acids, conversion to fatty acids takes place in the liver. The fatty acids offered with high-fat diets, as well as increased self-production of fats, lead to a deposition of triglycerides in the liver cells, which can lead to steatosis hepatis (fatty liver).
      • High consumption of table salt ?
      • High alcohol intake (↑)
    • Too low a proportion of complex carbohydrates
    • Diet low in fiber
    • Constant availability of food
    • Eating behavior (eating too fast; eating until you feel full).
    • Micronutrient deficiency (vital substances) – see prevention with micronutrients.
  • Consumption of stimulants
    • Alcohol – Excessive alcohol consumption (weight gain due to alcohol addition; 1 g of alcohol provides 7.1 kcal)
    • Tobacco (smoking) – Smokers who smoke more than 20 cigarettes daily (heavy smokers) have both higher body weight and BMI significantly above the averages for nonsmokers
  • Physical activity
    • Lack of exercise (increased sedentary activity) – it results in a reduced basal metabolic rateWith the same eating behavior, a positive energy balance (= weight gain), for example, immobilization after surgery, etc. arises.
  • Psycho-social situation
    • Mental reasons such as frustration and boredom.
    • Stress – the cerebral cortex sends increased signals to the amygdala and hippocampus under stress. Both areas activate the hypothalamus, which stimulates the increased release of stress hormones such as cortisol. These direct glucose to the brain and glucose uptake in the body is inhibited. When information processing is disturbed, the brain thus permanently demands energy, resulting in an imbalance between energy intake and energy consumption. The result is a positive energy balance and means weight gain. Caution. The increased glucocorticoid release leads primarily to the formation of visceral fat (abdominal fat).
    • In children continued to show excessive television and video games, as well as sleep deprivation as other causes.
  • Sleep duration
    • Sleep duration < 5 hours
    • Sleep deprivation in women: Women with five hours of sleep had 1.1 kg and those with six hours had 0.7 kg more than the comparison group with seven hours. In this respect, the authors suggest that sleep deprivation lowers basal metabolic rate by disrupting the day-night rhythm and, consequently, glucose and hormone metabolism.
    • Too little sleep (< 6 hours) impairs not only the metabolism of insulin, but also that of leptin – a satiety hormone – which also increases the risk of overweight or obesity.
  • Pregnancy

Causes due to disease

  • Age-related hyperleptinemia, which can develop into leptin resistance.
  • Depression
  • Endocrine disorders
    • Cushing’s syndrome – group of disorders leading to hypercortisolism (hypercortisolism) – oversupply of cortisol.
    • Diabetes mellitus type 2
    • PCO syndrome (Stein-Leventhal syndrome, polycystic ovary/ovary syndrome).
    • HVL insufficiency (failure of endocrine functions of the anterior pituitary, HVL).
    • Hyperinsulinism (islet cell adenoma; very rare benign tumor of the pancreatic islet organ).
    • Male hypogonadism (testicular hypofunction): the fat content is increased (gynoid habitus).
    • Hypothyroidism (hypothyroidism).
    • hypothalamic disorders:
      • Dystrophia adiposogenitalis (synonym: Fröhlich syndrome; hypothalamic syndrome, Babinski-Fröhlich syndrome) – syndrome associated with obesity (adiposity) of the female fat distribution type, short stature and other endocrine disorders. The cause of this disorder is a pituitary or hypothalamic tumor; frequency: rare.
      • Posttraumatic damage: Z. n. Radiatio (radiotherapy), surgery.
    • Klinefelter syndrome – gonosome abnormality of the male sex, which leads to primary hypogonadism (dysfunction of the testis) and thus a testosterone deficiency.
  • Eating disorders – e.g. Binge Eating Disorder (BED).
  • Brain tumor

Medications (Subsequent medications increase appetite or decrease energy expenditure – increased body weight is the result).

Operations

  • Some surgeries can lead to immobilization (bedriddenness) and thereby promote obesity
  • Certain surgeries: e.g., caesarean section (cesarean section); note: the intestine contains fewer bifidobacteria and more staphylococci.

Environmental pollution – intoxications (poisonings).

  • Bisphenol A (BPA) as well as bisphenol S (BPS) and bisphenol F (BPF) are associated with obesity in children; detection of BPF (versus no detection) showed an association with abdominal obesity (OR 1.29) and BMI (BPA is considered an endocrine disruptor and obesogen)
  • Phthalates (plasticizers used in the plastics industry), these occur especially in fatty products (cheese, sausage, etc.) overNote: Phthalates belong to the endocrine disruptors (synonym: xenohormones), which even in the smallest amounts can damage health by altering the hormonal system.

Other causes

  • Antibiotic therapy for prolonged periods
  • Frequent infections in the first year of life: each untreated infection in the first year of life increased risk by 25% (odds ratio 1.25; 95% confidence interval 95% CI 1.20-1.29), but not antibiotic therapy
  • Traumatic brain injury (TBI).
  • Pregnancy (gravidity) – about 20-30% of pregnant women are affected by obesity.
  • Climacteric / menopause (menopause in women).
  • Neuroticism and impulsivity – i.e. overweight people are worse at aligning their actions with long-term consequences. Overweight people are also more extroverted and receptive to rewards than normal weight people.