Effect of rosuvastatin on the concentration of each fatty acid in the fraction of free fatty acids and total lipids in human plasma: The role of cholesterol homeostasis

Abstract

Each fatty acid (FA) or class of FAs has a different behavior in the pathologies of atherosclerosis. The aim of this study was to investigate changes in the concentration of each fatty acid in the fraction of free fatty acids (FFAs) and total lipids in human plasma after short-term therapy with rosuvastatin as a cholesterol-lowering statin drug. Six hypercholesterolemic men on a habitual diet were studied in a randomized, double-blind, and crossover process. They received 20 mg rosuvastatin or placebo in random order, each for 4 weeks and after 2 weeks of washout period, they received another medication (placebo or rosuvastatin) for another period of 4 weeks. Rosuvastatin treatment significantly decreased the absolute concentrations of saturated and monounsaturated FAs in the total FAs as well as in FFAs. Long chain polyunsaturated fatty acids with 20 and 22 carbon atoms in the molecule had no significant change in the fraction of FFAs. Rosuvastatin is directly involved in cholesterol biosynthesis and indirectly through cholesterol homeostasis in the biosynthesis of other plasma lipids. In conclusion, our findings show that rosuvastatin treatment leads to significant changes in the concentration of each fatty acid, except for long-chain polyunsaturated fatty acids in FFAs. Our observations indicate that cholesterol homeostasis through its regulatory mechanisms appears to be the main cause of changes in the concentration of each plasma fatty acid during rosuvastatin treatment. These changes can be a source of beneficial consequences, in addition to lowering low-density lipoprotein cholesterol in cardiovascular diseases.

Association of Metabolomic Change and Treatment Response in Patients with Non-Alcoholic Fatty Liver Disease

“…We expect that the reduction in the levels of these metabolites is a consequence of rosuvastatin treatment rather than the underlying mechanisms of NAFLD because these lipid metabolites are the sources of hepatic lipid accumulation. Statins inhibit the production of cholesterol, which in turn significantly decreases the level of saturated and monounsaturated FAs in total FAs, and exceptionally, octadecenoic acid (C18:1) and octadecadienoic acid (C18:2) [ 54 ]. Another study showed that strong statins, such as rosuvastatin, decreased the DHA levels, although the mechanism is unknown, suggesting that DHA added to the statin would improve the clinical effects [ 55 ].…”

The role of hepatic lipid composition in obesity‐related metabolic disease

“…127 In vivo, data are currently restricted to plasma fatty acid compositions (which may not reflect hepatic lipid composition); however, these studies found that statins increase the proportion of long-chain PUFAs and decrease the proportion of SFAs and MUFAs. 128,129 Furthermore, statin treatment also led to elevations in the n-6/n-3 PUFA ratio 130 ; however, the physiological role this plays in their mode of action remains unclear. Additional studies are required to determine the impact of statins on hepatic lipid composition.…”

“…Nevertheless, preclinical research suggests that statins may also alter lipid composition in multiple cell lines including human liver cells 127 . In vivo , data are currently restricted to plasma fatty acid compositions (which may not reflect hepatic lipid composition); however, these studies found that statins increase the proportion of long‐chain PUFAs and decrease the proportion of SFAs and MUFAs 128,129 . Furthermore, statin treatment also led to elevations in the n ‐6/ n ‐3 PUFA ratio 130 ; however, the physiological role this plays in their mode of action remains unclear.…”

Arachidonic acid is associated with dyslipidemia and cholesterol-related lipoprotein metabolism signatures

“…These species vary in the lengths of their carbon chains and their level of saturation. Numerous lines of evidence indicate that high free FA and TG concentrations increase the risks of atherosclerotic cardiovascular disease and mortality ( 4 ). However, in routine clinical laboratory testing, the total serum FA and TG concentrations are typically measured.…”