Hypothyroid and adrenal mechanisms
The development of excess body weight in hypothyroidism is associated with a deficiency of iodine-containing thyroid hormones (T3, T4). Under these conditions, metabolic rates and the body's energy expenditure drop, while lipolysis processes are inhibited.
In the adrenal (cortisol) mechanism, observed in Cushing's disease or syndrome, the adrenal cortex overproduces glucocorticoids. This triggers a cascade of disorders:
- Gluconeogenesis is activated, leading to hyperglycemia.
- Glucose transport into adipocytes is enhanced.
- Glycolysis is activated in adipose tissue.
- Lipolytic reactions are suppressed, resulting in the accumulation of triglycerides.
Insulin and leptin variants
The endocrine mechanisms of obesity also include the insulin factor. Its essence lies in an increased number of insulin receptors and/or their enhanced sensitization. As a result, active lipogenesis is triggered in adipocytes, leading to the excessive accumulation of adipose tissue.
Among the most significant variants of endocrine genesis are:
- The leptin (adipokine) mechanism.
- The hypothyroid mechanism.
- The adrenal mechanism.
- The insulin mechanism.
The role of the endocannabinoid system
The endocannabinoid system plays a crucial role in regulating the body's energy balance. It interacts closely with the limbic system, the gastrointestinal tract, and adipose tissue.
Normally, cannabinoids participate in metabolic processes, but in obesity, the activity of this system increases, contributing to a further increase in body weight.
Metabolic features and fat oxidation
In the human body, carbohydrate reserves are extremely small and comparable to daily consumption, which evolutionary mechanisms have fixed as a "conservation" strategy.
If the proportion of fats in the diet increases, the rate of carbohydrate oxidation naturally decreases. The marker of this process is a decrease in the respiratory quotient — the ratio of carbon dioxide production rate ($CO_2$) to oxygen consumption ($O_2$).
The pathology develops through the following chain:
- The mechanism of glycogenolysis inhibition is disrupted when blood fat concentrations are high.
- The appetite-increasing center is activated.
- The volume of food consumed increases.
- Excess nutrients are deposited as triglycerides.
Briefly: answers to topical questions
What is the mechanism of development of leptin-related obesity?
The mechanism of leptin-related obesity is associated with absolute or relative leptin deficiency. Additionally, in obese individuals, the mechanism of leptin action may be impaired due to leptin resistance or leptin gene mutation.
Normally, adipose tissue secretes leptin. Leptin acts on neurons in the hunger and satiety centers of the hypothalamus and reduces the synthesis and release of neuropeptide Y, which causes the sensation of hunger.
When this mechanism is disrupted, the following develop:
- increased sensation of hunger;
- increased appetite;
- excessive food intake.
The result is obesity.
What other adipokines, besides leptin, are secreted by adipose tissue and influence the development of obesity?
In addition to leptin, the main adipokines include:
- adiponectin;
- resistin;
- ghrelin.
Adiponectin is secreted by adipocytes; in obesity, a decrease in its secretion is observed. Adipokine imbalance in obesity potentiates the development of insulin resistance and disrupts free fatty acid metabolism.
The four pillars of endocrine obesity are TILN (Thyroid, Insulin, Leptin, Adrenal).
Class and exam questions
Which thyroid hormones cause the hypothyroid variant of obesity?
Deficiency in the effects of iodine-containing thyroid hormones—T3 and T4.
How do glucocorticoids affect carbohydrate metabolism in adipocytes?
Excess glucocorticoids activate gluconeogenesis, causing hyperglycemia, after which glucose transport into adipocytes is enhanced and glycolysis is activated.
What happens to the endocannabinoid system in obesity?
In obesity, the activity of the endocannabinoid system increases, which contributes to further body weight gain.
What else to study on this topic
- Pathogenesis of hypothyroid obesity at the level of lipolysis
- Molecular effects of glucocorticoid excess
- The role of insulin receptors in lipogenesis
- Functions of leptin and adipokines
- Respiratory quotient on a high-fat diet
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