SN2
SHORT NOTE
5M
★ High-yield
Define fatty liver. Describe its causes and mechanisms. Add a note on lipotropic factors.
Definition
Fatty liver (hepatic steatosis) = abnormal accumulation of triglyceride in hepatocytes, exceeding 5% of liver weight.
Mechanism — the Balance
Fat arriving at the liver — free fatty acids from adipose tissue, dietary chylomicron remnants, de novo lipogenesis → vs → Fat leaving the liver — β-oxidation, and export as VLDL → Imbalance → triglyceride accumulates
Causes Grouped BY Mechanism
| Mechanism | Causes |
|---|---|
| ↑ Supply of fatty acids | Obesity, diabetes, starvation, high-fat diet, corticosteroids |
| ↑ De novo lipogenesis | High carbohydrate and fructose intake, insulin resistance |
| ↓ β-oxidation | Alcohol (↑ NADH), carnitine deficiency, tetracycline |
| ↓ VLDL export | Choline or protein deficiency (kwashiorkor), carbon tetrachloride, puromycin (block apoprotein synthesis), abetalipoproteinaemia |
Alcohol — WHY It Is So Potent
- Alcohol oxidation generates a large excess of NADH
- The high NADH:NAD+ ratio inhibits β-oxidation and the TCA cycle
- It also favours triglyceride synthesis from the accumulating glycerol-3-phosphate
- Acetaldehyde damages the microtubules needed for VLDL secretion
- The result is the earliest and most reversible stage of alcoholic liver disease
Lipotropic Factors
Lipotropic factors = substances that prevent or reverse fatty liver, chiefly by promoting phospholipid synthesis and hence VLDL export.
| Factor | Role |
|---|---|
| Choline | Directly needed for phosphatidylcholine (lecithin), the chief phospholipid of the VLDL surface |
| Methionine | Provides methyl groups via SAM to make choline |
| Betaine, folate, vitamin B12 | Support methyl group transfer |
| Essential fatty acids | Phospholipid synthesis |
| Vitamin E and selenium | Antioxidant protection |
Applied Aspects
- Non-alcoholic fatty liver disease (NAFLD) is now the commonest liver disease worldwide and the hepatic manifestation of the metabolic syndrome
- It may progress: steatosis → steatohepatitis (NASH) → fibrosis → cirrhosis → hepatocellular carcinoma
- Simple steatosis is reversible — weight loss, exercise, control of diabetes and stopping alcohol are the mainstay; no drug is firmly established
- Reye syndrome — acute microvesicular fatty liver with encephalopathy in children given aspirin during a viral illness
All questions in Lipid Metabolism
- Q1Describe the β-oxidation of fatty acids. Explain the carnitine shuttle, the energetics for palmitate, and the regulation of the pathway. ★
- Q2Describe the synthesis and utilisation of ketone bodies. Explain the causes of ketosis and the biochemical basis of diabetic ketoacidosis. ★
- Q3Describe the de novo synthesis of fatty acids. Explain the citrate shuttle, the role of acetyl-CoA carboxylase, and compare it with β-oxidation. ★
- Q4Describe the biosynthesis and regulation of cholesterol. Give its functions, transport and fate. Add a note on hypercholesterolaemia. ★
- Q5Classify the plasma lipoproteins. Describe their metabolism and the role of apolipoproteins. Add a note on the hyperlipoproteinaemias. ★
- SN1Describe the carnitine shuttle and its regulation. ★
- SN2Define fatty liver. Describe its causes and mechanisms. Add a note on lipotropic factors. ★
- SN3Define essential fatty acids. Give their sources, functions and the features of deficiency. ★
- SN4Describe the synthesis and actions of the eicosanoids. Explain the action of aspirin. ★
- SN5Describe lipoprotein lipase with its site, activator and significance.
- SN6Classify phospholipids and describe their functions. Add a note on lung surfactant. ★
- SN7Describe the biochemical basis of atherosclerosis and the lipid risk factors. ★