Table 2.

Adiposopathy: Causality and illustrative anatomic, pathophysiologic, and clinical manifestations. [14••, 41••]

Causes of adiposopathy

• Positive caloric balance

• Sedentary lifestyle

• Genetic predisposition

• Environmental causes (e.g. certain medications, viral infections, pathologic gut microbiota signaling)

Anatomic manifestations of adiposopathy

• Adipocyte hypertrophy

• Increased visceral, pericardial, perivascular, and other periorgan adiposity

• Growth of adipose tissue beyond its vascular supply with ischemia, cellular death, apoptosis, and inflammation

• Increased number of adipose tissue immune cells

• “Ectopic fat deposition” in other body organs (liver, muscle, pericardial fat, perivascular fat, and possibly pancreas)

Pathophysiological manifestations of adiposopathy

• Impaired adipogenesis

• Pathological adipocyte organelle dysfunction (e.g. “stress” to adipocyte endoplasmic reticulum, mitochondria)

• Increased circulating free fatty acids (lipotoxicity)

• Pathogenic adipose tissue endocrine responses (e.g., increased leptin, increased tumor necrosis factor-alpha, decreased adiponectin, and increased mineralocorticoids)

• Pathogenic adipose tissue immune responses (e.g., increased proinflammatory responses through increased tumor necrosis factor-alpha and decreased anti-inflammatory responses through decreased adiponectin)

• Pathogenic interactions or pathogenic cross talk with other body organs (e.g., liver, muscle, central nervous system, and vasculature.)

Clinical manifestations of adiposopathy

• High glucose blood levels (prediabetes, type 2 diabetes mellitus)

• Insulin resistance

• High blood pressure

• Adiposopathic dyslipidemia

○ Increased triglyceride, triglyceride rich lipoprotein, and lipoprotein remnant levels

○ Decreased high density lipoprotein cholesterol levels

○ Increased atherogenic particle number (i.e. increased apolipoprotein B)

○ Increased small dense low density lipoprotein particles

• Metabolic syndrome

• Atherosclerosis

• Fatty liver

• Hypoandrogenemia in men

• Hyperandrogenemia in women

• Polycystic ovarian syndrome, menstrual disorders, and infertility

• Hyperuricemia

• Cholelithiasis

• Glomerulopathy

• Prothrombotic state

• Cancer

• Other inflammatory diseases (e.g. worsening depression, asthma, osteoarthritis)

Illustrative causes of metabolic diseases not due to adiposopathy

• Type 2 diabetes mellitus may be due to hemochromatosis, chronic pancreatitis, hypercortisolism, excessive growth hormone, genetic syndromes of insulin resistance, and decreased pancreatic function (genetic syndromes, surgical excision, etc.).

• High blood pressure may be due to pheochromocytoma, primary hyperaldosteronism, hypercortisolism, hyperthyroidism, renal artery stenosis, various kidney diseases, and familial or genetic syndromes.

• Dyslipidemia may be due to untreated hypothyroidism, poorly controlled diabetes mellitus, certain types of liver or kidney diseases, and genetic dyslipidemias.