10. Regulation and disorders of lipid metabolism

Last updated on November 19, 2018 at 17:16


  • AMPK increases β-oxidation, decreases fatty acid synthesis
  • Insulin increases fatty acid synthesis, decreases β-oxidation
  • Epinephrine induces lipid breakdown in adipocytes
  • Mitochondrial HMG-CoA synthase is inhibited by succinyl-CoA
  • PPAR’s are ligand-activated transcription factors that control
  • Hypercholeserolemia is treated with HMG-CoA reductase inhibitors called statins
  • In diabetes mellitus, insulin isn’t produced or effective, so myocytes and adipocytes cannot take in glucose. The cells respond by creating so much ketone bodies that acidosis occurs.


AMPK, which is activated when ATP is low or in response to adiponectin or leptin, will activate β-oxidation and decrease fatty acid synthesis. This makes sense, because when ATP is low, energy is low, so stored energy should be burned.

Insulin, the enzyme secreted right after a meal, will decrease β-oxidation and increase fatty acid synthesis.

Epinephrine induces the breakdown of triacylglycerols into glycerol and 3 fatty acids, by the mechanism of hormone-sensitive lipase.

Mitochondrial HMG-CoA synthase is inhibited by succinyl-CoA, an intermediate in the citric acid cycle. So that, if the citric acid cycle has sufficient amounts of intermediates and therefore energy, the cell will not produce ketone bodies.

PPARs are ligand-activated transcription factors, which means that they are activated when they bind something. There are 4 types of PPARs, PPARα, PPARβ, PPARδ, and PPARγ.

PPARγ is activated by thiazolidinedione, a drug used to treat diabetes type 2. Activation of it increases lipid storage and synthesis, and increased PEPCK expression in adipose tissue.

PPARβ and PPARδ sense changes in dietary lipid. They encode genes necessary for β-oxidation, and for uncoupling of mitochondria. Uncoupling of mitochondria leads to less effective oxidative phosphorylation, which causes increased energy use and heat production. Activation of these are targets for medication for treating obesity.

PPARα is activated by eicosanoids (20 carbon long fatty acids that are signalling molecules). It turns on genes necessary for uptake and oxidation of fatty acids, which lowers triacylglycerol content in the blood. PPARα agonists are used to treat coronary heart disease.


Hypercholesterolemia is a condition where you have increased level of cholesterol and LDL in the blood. It leads to coronary heart disease and myocardial infarction. It is treated with HMG-CoA reductase inhibitors called statins.

Diabetes exists in two types. In type 1, the insulin-producing beta cells in the pancreas don’t produce insulin, while in type 2, insulin production is impaired while cells have limited ability to respond to it. Type 2 is treated with thiazolidinedione, which is a PPARγ agonist.

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9. Synthesis of cholesterol and ketone bodies

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11. Amino acid metabolism; the fate of the amino group

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