Accelerated Hepatic Lipid Synthesis in Fasted Septic Rats

Abstract

We examined changes in the enzyme activities and metabolites related to hepatic fatty acid synthesis in fasted rats with sepsis produced by cecal ligation and puncture. Sepsis stimulated the in vivo incorporation of tritiated water into hepatic fatty acids and nonsaponifiable lipids. The activities of acetyl-CoA carboxylase, ATP-citrate lyase, and NADPH-generating enzymes (glucose-6-phosphate dehydrogenase and malic enzyme), the tissue levels of citrate and malonyl-CoA, and the dephosphorylation of carboxylase were increased in the livers of fasted septic rats compared with fasted sham-operated control rats. These results indicate that sepsis stimulated hepatic lipogenesis and sterologenesis in fasting rats. Furthermore, sepsis reduced the specific activity of hepatic mitochondrial carnitine palmitoyltransferase and raised that of glycerophos-phate acyltransferase, suggesting an increased diversion of cytosolic acyl-CoA towards esterification. These intrahepatic metabolic changes strongly suggest that sepsis causes anabolic action on hepatic lipid metabolism.

ω-3 vs. ω-6 lipid emulsions exert differential influence on neutrophils in septic shock patients: impact on plasma fatty acids and lipid mediator generation

“…Several factors may underlie this metabolic response: (a) Plasma free fatty acid elevation is a component of the general metabolic response syndrome to stress [41]. (b) Lipolysis from adipocytes and hepatic de novo lipogenesis are increased in sepsis [42,43,44,45], and muscle fatty acid oxidation is reduced [46]. (c) Secretory phospholipase A 2 is elevated in sepsis [47].…”

Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host

“…Late increases in ACC activity in rat liver occur in a sepsis model induced by cecal ligation and puncture (57). Whether gene expression of ACC and/or FAS increases in the liver is currently not known.…”

Cyclosporine A attenuates cardiac dysfunction induced by sepsis via inhibiting calcineurin and activating AMPK signaling

“…Sepsis-induced alterations in myocardial energy metabolism serve an important role in the development of cardiac dysfunction (29). Altered myocardial energy metabolism is characterized by impaired mitochondrial function, reduced lipid metabolism and glucose metabolism disorders in patients and mouse models (20). Myocardial NEFA accumulation is an important manifestation of myocardial metabolic dysregulation (20).…”

“…Altered myocardial energy metabolism is characterized by impaired mitochondrial function, reduced lipid metabolism and glucose metabolism disorders in patients and mouse models (20). Myocardial NEFA accumulation is an important manifestation of myocardial metabolic dysregulation (20). Under physiological conditions, cardiomyocytes do not synthesize and store a significant quantity of NEFA; instead, myocardial cells take up NEFA from the circulating serum.…”

“…The AMP-activated protein kinase (AMPK)-acetyl CoA carboxylase (ACC)-carnitine palmitoyl transferase 1 (CPT1) signaling pathway is one of the pathways involved in mediating myocardial energy metabolism (18,19). The AMPK-ACC-CPT1 pathway is activated in response to hormone signaling and stressors, including low blood glucose levels, hypoxia and ischemia (20). A previous study demonstrated that elevated calcineurin activity interferes with AMPK-ACC-CPT1 pathway function, whereas CSA ameliorated fatty acid metabolism by inhibiting calcineurin activity in rodent hippocampi (3).…”