Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice

The synthesis of TGs in liver is nutritionally regulated. The ingestion of a LF/HC diet causes a marked induction of enzymes involved in key metabolic pathways, including (i) glucokinase (GK) and L-PK for glycolysis; (ii) ATP citrate lyase, ACC, and FAS for lipogenesis; (iii) ELOVL6 and SCD1 for fatty acid elongation and desaturation steps; and finally (iv) GPAT and DGAT for TG synthesis. Under these nutritional conditions, elevation in malonyl-CoA concentrations, the product of the lipogenic enzyme ACC, inhibits L–CPT I, the rate-limiting enzyme of β-oxidation (v), which regulates the transfer of long-chain acyl-CoAs from the cytosol into the mitochondria, thus resulting in a shift from an oxidative (production of ketone bodies) to an esterification pathway (TG synthesis). F6P, fructose 6-phosphate; F1, 6P2, fructose 1,6 diphosphate; G3P, glycerol 3-phosphate; G6P, glucose 6-phosphatase; PEP, phosphoenol pyruvate; LCFA, long-chain fatty acids; CPT II, carnitine palmitoyltransferase II.

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Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. (2008) Catherine Postic, et al. J Clin Invest. 2008 Mar 3;118(3):829-838. Figure: F3. All organisms Homo sapiens Mus musculus Drosophila melanogaster

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