Fat metabolism = digestion, transport, storage, breakdown, and synthesis of lipids. It underpins energy homeostasis, allowing the body to switch from carbohydrates to triglycerides during fasting or exercise. Fats are the most energy-dense macronutrient (~9 kcal/g vs 4 kcal/g for carbohydrate or protein).

🍽️ Digestion & Absorption

🔪 Pancreatic lipase breaks triglycerides → free fatty acids + monoglycerides.
🫧 Bile salts emulsify fats into micelles for absorption by enterocytes.
🚚 Re-esterified triglycerides packaged into chylomicrons → lymphatics → blood.

🚚 Transport of Lipids

Chylomicrons – dietary triglycerides & cholesterol → tissues.
VLDL – hepatic triglycerides → tissues.
LDL – delivers cholesterol to cells (atherogenic).
HDL – reverse cholesterol transport → liver.
💡 Lipoprotein lipase hydrolyses TG in chylomicrons/VLDL → free fatty acids for storage or oxidation.

🔥 Mobilisation of Stored Fat

Fasting/exercise → ↓ insulin, ↑ glucagon & adrenaline.
➡️ Activates hormone-sensitive lipase in adipocytes.
Releases free fatty acids (bound to albumin) + glycerol (to liver for gluconeogenesis).

⚙️ β-Oxidation of Fatty Acids

Fatty acids activated → acyl-CoA.
🚪 Carnitine shuttle (CPT-I, translocase, CPT-II) moves long-chain FA into mitochondria.
Cycle: dehydrogenation (FADH₂), hydration, dehydrogenation (NADH), thiolysis → acetyl-CoA.
⚡ Acetyl-CoA → TCA cycle; NADH/FADH₂ → ETC. One palmitate (16C) yields ~106 ATP!

🍐 Ketogenesis

Occurs in liver during prolonged fasting, uncontrolled diabetes, or low-carb diet.
Excess acetyl-CoA → ketone bodies (acetoacetate, β-hydroxybutyrate, acetone).
🧠 Brain & muscle use ketones when glucose is scarce. Excess → ketoacidosis.

🏭 Fatty Acid Synthesis (Lipogenesis)

Fed state, excess acetyl-CoA exported (via citrate shuttle) to cytoplasm.
Acetyl-CoA carboxylase → malonyl-CoA (committed step).
Fatty acid synthase → palmitate (16C). Can be elongated/desaturated.
Stored as triglycerides in adipose tissue.

⚖️ Regulation

🧪 Insulin → ↑ lipogenesis, ↓ lipolysis.
⚡ Glucagon & adrenaline → ↑ lipolysis & β-oxidation.
🔋 AMPK → energy sensor: promotes catabolism, suppresses synthesis.

⚠️ Clinical Relevance

🩸 Diabetes Mellitus – uncontrolled lipolysis & ketogenesis → diabetic ketoacidosis (DKA).
⚖️ Obesity – chronic energy surplus → ↑ triglyceride storage, insulin resistance, NAFLD.
💉 Hyperlipidaemia – ↑ LDL/VLDL → atherosclerosis & CVD risk.
🧬 Carnitine deficiency – impaired β-oxidation → hypoketotic hypoglycaemia.

📌 Summary

Fat metabolism balances storage 🥓 and use 🔥. Key processes: digestion, transport, β-oxidation, ketogenesis, and fatty acid synthesis. Hormones (insulin, glucagon, adrenaline) orchestrate this. Dysregulation contributes to obesity, diabetes, fatty liver, and cardiovascular disease.

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Fat Metabolism

🥓 Overview of Fat Metabolism