Pathomechanism of obesity and its consequences, examples

1. Definition

Obesity = increased body weight from adipose-tissue accumulation sufficient to cause adverse health effects. Measured by BMI = weight (kg) / height (m²); BMI >30 confers health risk (overweight 25–29.9, obese 30–34.9, severe 35–39.9, morbid ≥40).

2. Etiology

• Genetic — sex; syndromes (Prader-Willi, Laurence-Moon-Biedl, Klinefelter); leptin / leptin-receptor gene mutations.
• Environmental — excess intake, physical inactivity, socio-cultural/economic factors.
• Metabolic — hypothyroidism, Cushing’s disease.

3. Fat distribution

• Central/visceral (“apple”) — trunk/abdominal fat; metabolically dangerous.
• Peripheral/subcutaneous (“pear”) — below the waist; lower risk.

4. Pathomechanism — energy balance & adipose endocrine signals

Intake > expenditure → adipocyte hypertrophy/hyperplasia. Regulated by hypothalamic anabolic vs catabolic circuits responding to adiposity signals:

Hormone	Source	Effect on intake
Leptin	Adipocytes (LEP gene)	↓ intake (POMC/CART ↑, NPY/AgRP ↓) — “stop eating”; leptin resistance in obesity
Adiponectin	Adipocytes	“Fat-burning”; low in obesity; ↑ insulin sensitivity, anti-inflammatory/anti-atherogenic
Ghrelin	Stomach	↑ intake (stimulates NPY/AgRP)
Peptide YY (PYY)	Ileum/colon	↓ intake (satiety)

Visceral adipose = endocrine organ: ↑ TNF-α/IL-6, ↓ adiponectin → chronic low-grade inflammation + insulin resistance.

5. Consequences

• Metabolic syndrome — central obesity + dyslipidemia (↑ TG, ↓ HDL) + hypertension + hyperglycemia → ↑ atherosclerosis.
• T2DM (insulin resistance/hyperinsulinemia), NAFLD/NASH → cirrhosis, CAD/stroke, obstructive sleep apnea / obesity-hypoventilation (Pickwickian), osteoarthritis, cholelithiasis; ↑ CRP/TNF.
• Cancers (mechanism: ↑ insulin/IGF-1, steroid hormone effects, ↓ adiponectin, pro-inflammatory state):
  • Men — esophagus, thyroid, colon, kidney (~14% of cancer deaths).
  • Women — esophagus, endometrium, gallbladder, kidney, postmenopausal breast (~20% of cancer deaths).

💡 High-yield: Obesity = BMI >30; central/visceral (“apple”) is dangerous. Leptin = “stop eating” (resistance in obesity); adiponectin low in obesity; ghrelin ↑ / PYY ↓ appetite. Visceral fat → TNF/IL-6 → insulin resistance → metabolic syndrome, T2DM, NAFLD, OSA; cancers via insulin/IGF-1 (endometrial, colon, breast).