Obesity syndrome

Cellular mechanisms and pathomorphology

The proliferation of adipose tissue at the cellular level is biphasic. The morphological basis of the process is initially hypertrophy (existing adipocytes accumulate triglycerides and critically increase in size), followed by hyperplasia. When the cellular volume limit is exhausted, preadipocyte differentiation into new fat cells is triggered.

Depending on the predominance of a particular process, three morphological types of obesity are distinguished: hypertrophic, hyperplastic, and mixed.

Under the microscope, adipocytes appear giant, with the nucleus displaced to the periphery. In visceral obesity, signs of cellular stress and macrophage infiltration of the tissue are observed. This creates a focus of chronic low-grade inflammation, which is a crucial link in the development of tissue insulin resistance.

Macroscopically, excess adipose tissue is localized in the subcutaneous layer, omentum, mesentery, and retroperitoneal space. Damage to internal organs is particularly dangerous:

• Liver and pancreas: fatty hepatosis (steatosis) develops.
• Heart: fat grows under the epicardium and into the myocardial stroma between muscle fibers. Fatty infiltration and dystrophy occur, compressing cardiomyocytes. Heart cells atrophy and thin ("fatty heart"), which in severe cases threatens a fatal wall rupture.

Endocrine mechanisms of development

The pathogenesis of obesity is often based on hormonal shifts. In general pathophysiology, several key mechanisms are identified:

1. Adrenal type. Occurs with an excess of glucocorticoids. They activate gluconeogenesis, causing hyperglycemia. Excess glucose is transported into adipocytes, where glycolysis is initiated and lipolysis (fat breakdown) is sharply inhibited.
2. Insulin type. Insulin directly stimulates lipogenesis. Hyperinsulinemia (even in the setting of resistance) forces adipose tissue to actively deposit triglycerides.
3. Hypothyroid type. Thyroid hormone deficiency leads to a global decrease in basal metabolic rate and delayed lipolysis.
4. Hypothalamic type. Malfunction in the hunger and satiety centers (ventromedial and lateral nuclei of the hypothalamus), as well as loss of receptor sensitivity to leptin (leptin resistance).
5. Gonadal type (hypogonadal). A decrease in sex hormone levels deprives the body of their natural lipolytic effect.

Association with metabolic syndrome and diabetes

Visceral obesity is the foundation of metabolic syndrome. Excess adipose tissue triggers an enhanced release of leptin and calcitonin gene-related peptide. These substances act as insulin inhibitors.

As a result, relative insulin deficiency and insulin resistance develop, with impairments fixed at all levels: prereceptor, receptor, and postreceptor. In most patients, the requirement for insulin increases, which creates an ideal environment for the manifestation of type 2 diabetes mellitus. This is why targeted weight reduction is recognized as the primary preventive measure.

Complications and target-organ damage

Excess weight is systemic in nature and affects all body systems. The main complications include:

• Endocrine and metabolic: impaired fasting glucose, impaired glucose tolerance, dyslipidemia (hypercholesterolemia, hypertriglyceridemia, or a combination thereof).
• Cardiovascular: development of persistent arterial hypertension.
• Hepatobiliary: non-alcoholic fatty liver disease with a risk of progression to steatohepatitis.
• Reproductive (in females): menstrual irregularities, ovarian dysfunction, development of polycystic ovary syndrome (PCOS).
• Musculoskeletal: pathologies caused by excessive mechanical stress on bones and joints.

In addition, patients suffer from psycho-emotional problems. Obesity is officially recognized as a risk factor for gout, rheumatoid arthritis, and, as part of metabolic syndrome, hepatocellular carcinoma.

Class and exam questions

What else to study on this topic

• Pathogenesis of insulin resistance: prereceptor, receptor, and postreceptor levels of impairment.
• Leptin resistance: effects on hypothalamic hunger and satiety centers.
• Metabolic syndrome: complete diagnostic triad and criteria for diagnosis.
• Morphological picture of non-alcoholic fatty liver disease (transition from steatosis to steatohepatitis).
• Association between visceral obesity and polycystic ovary syndrome (PCOS).

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Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.