2009B11 Describe the role of insulin in fat metabolism.

Summary

·   Peptide hormone

·   Synthesised and stored in islet β-cells

·   Release stimulated by ↑BSL more than ↑amino acids and ↑FFA Anabolic and pro-inflammatory effects in adults, growth factor in utero

·   ↑ de novo lipogenesis (DNL), ↓lipolysis

Cellular mechanism

·   Insulin receptor:

o Tyrosine kinase

o 2 x extracellular α-subunits, 2 x intracellular β-subunits

·   Binding of insulin:

o Autophosphorylation and activation of TK activity

o Signalling via PI3K (metabolic) and MAPK (inflammation etc.) pathways

In adipose

·   ↑GLUT4 expression -> ↑glucose uptake and trapping -> ↑glycerol synthesis

·   ↑endothelial LPL activity-> ↑FFA uptake from VLDL and chylomicrons

·   ↓HSL activity -> ↓TAG breakdown (opposite if catecholamines)

·   ↑activity of pyruvate dehydrogenase, Acetyl-CoA carboxylase -> ↑DNL -> ↑TAG storage

o i.e. glucose -> pyruvic acid -> acetyl CoA -> fatty acid

In liver

·   ↑Hexokinase activation -> ↑glucose uptake via GLUT2

·   ↑DNL via ↑PDH and ↑Acetyl-CoA carboxylase activity

·   ↑synthesis and release of lipoproteins (transports lipids to tissues)

·   ↑synthesis of cholesterol (HMGCoA reductase)

·   Inhibit synthesis of ketones (acetoacetate, β-OH-butyrate, acetone)

o Excess Acetyl CoA undergoes DNL rather than ketogenesis

In skeletal muscle

·   Once glycogen is replete: ↑DNL (minor)