adipocyte

**Types** - **White (unilocular) adipocytes:** One large lipid droplet, with the nucleus pushed to the periphery (signet-ring appearance). They store triglycerides, insulate, cushion, and secrete hormones. They make up most adult fat (subcutaneous and visceral). - **Brown (multilocular) adipocytes:** Many small lipid droplets with a central nucleus and abundant mitochondria (cytochrome-rich, hence the brown color). They carry out nonshivering thermogenesis through **UCP-1 (thermogenin)**, which uncouples oxidative phosphorylation from ATP synthesis so energy is released as heat. They are prominent in neonates (interscapular, perirenal) and are stimulated by cold through sympathetic β3-adrenergic signaling. Adults retain small amounts, and pheochromocytoma can increase brown fat activity. - **Beige (brite) adipocytes:** Inducible thermogenic cells within white fat, induced by cold or β3 stimulation.

**Origin:** Mesenchymal stem cells differentiate into preadipocytes and then adipocytes. The master regulator is **PPAR-γ**, which is the target of thiazolidinediones (pioglitazone). These drugs increase insulin sensitivity.

**Lipid metabolism** - **Fed state (insulin):** Insulin increases GLUT4 expression and glucose uptake. It also stimulates **lipoprotein lipase (LPL)**, which releases fatty acids from chylomicrons and VLDL for uptake. Triglycerides are re-esterified using glycerol-3-phosphate, which comes from glucose because adipocytes lack glycerol kinase. - **Fasting (glucagon, epinephrine):** These hormones activate **hormone-sensitive lipase (HSL)** through cAMP/PKA. Insulin inhibits HSL. Free fatty acids are released, bound to albumin, and delivered to tissues for oxidation. Glycerol goes to the liver for gluconeogenesis.

**Endocrine functions** - **Leptin:** Signals satiety to the hypothalamus (acts on the arcuate nucleus, inhibiting NPY and stimulating POMC). Levels correlate with fat mass. Leptin deficiency causes severe early-onset obesity. Low leptin occurs in starvation. - **Adiponectin:** Improves insulin sensitivity and is anti-inflammatory. It is **decreased** in obesity and metabolic syndrome. - **Others:** TNF-α, IL-6, and resistin contribute to insulin resistance. Aromatase in adipose tissue converts androgens to estrogens, causing gynecomastia in obese men and increasing postmenopausal estrogen. Adipose tissue also produces angiotensinogen.

**Clinical correlations** - **Hypertrophy vs hyperplasia:** Adult obesity occurs mainly through hypertrophy, while childhood-onset obesity involves hyperplasia as well. - **Obesity:** Associated with insulin resistance and type 2 diabetes, hypertension, dyslipidemia, NAFLD, and endometrial/breast cancer (through estrogen excess). It also raises the risk of obstructive sleep apnea, GERD, and osteoarthritis. - **Visceral adiposity:** More metabolically harmful than subcutaneous fat. - **Lipoma:** A benign tumor of adipocytes, which is common. - **Liposarcoma:** A malignant tumor of adipocytes. It is associated with MDM2/CDK4 amplification (well-differentiated/dedifferentiated types) and lipoblasts on histology. - **Fat necrosis:** Seen in the breast after trauma, and in acute pancreatitis as **saponification** (enzymatic fat necrosis). - **Lipodystrophy:** Loss of adipose tissue leads to insulin resistance and hypoleptinemia. It can occur with HIV protease inhibitors. - **Prader-Willi syndrome:** Hyperphagia and obesity. Ghrelin is elevated. - **Histology:** Stains pale or empty on H&E because lipid is dissolved during processing. Frozen sections with Oil Red O or Sudan stains show the lipid.