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. |