Influence of Fenofibrate Treatment on Triacylglycerides, Diacylglycerides and Fatty Acids in Fructose Fed Rats
Overview
Authors
Affiliations
Fenofibrate (FF) lowers plasma triglycerides via PPARα activation. Here, we analyzed lipidomic changes upon FF treatment of fructose fed rats. Three groups with 6 animals each were defined as control, fructose-fed and fructose-fed/FF treated. Male Wistar Unilever Rats were subjected to 10% fructose-feeding for 20 days. On day 14, fenofibrate treatment (100 mg/kg p.o.) was initiated and maintained for 7 days. Lipid species in serum were analyzed using mass spectrometry (ESI-MS/MS; LC-FT-MS, GC-MS) on days 0, 14 and 20 in all three groups. In addition, lipid levels in liver and intestine were determined. Short-chain TAGs increased in serum and liver upon fructose-feeding, while almost all TAG-species decreased under FF treatment. Long-chain unsaturated DAG-levels (36:1, 36:2, 36:4, 38:3, 38:4, 38:5) increased upon FF treatment in rat liver and decreased in rat serum. FAs, especially short-chain FAs (12:0, 14:0, 16:0) increased during fructose-challenge. VLDL secretion increased upon fructose-feeding and together with FA-levels decreased to control levels during FF treatment. Fructose challenge of de novo fatty acid synthesis through fatty acid synthase (FAS) may enhance the release of FAs ≤ 16:0 chain length, a process reversed by FF-mediated PPARα-activation.
Elevated Kallistatin promotes the occurrence and progression of non-alcoholic fatty liver disease.
Fang Z, Shen G, Wang Y, Hong F, Tang X, Zeng Y Signal Transduct Target Ther. 2024; 9(1):66.
PMID: 38472195 PMC: 10933339. DOI: 10.1038/s41392-024-01781-9.
Shen J, Yu H, Li K, Ding B, Xiao R, Ma W Diabetes Metab Syndr Obes. 2022; 15:1423-1436.
PMID: 35573864 PMC: 9091472. DOI: 10.2147/DMSO.S353449.
Suto K, Fukuda D, Shinohara M, Ganbaatar B, Yagi S, Kusunose K J Atheroscler Thromb. 2021; 28(12):1349-1360.
PMID: 33775978 PMC: 8629704. DOI: 10.5551/jat.61101.
Fructose and hepatic insulin resistance.
Softic S, Stanhope K, Boucher J, Divanovic S, Lanaspa M, Johnson R Crit Rev Clin Lab Sci. 2020; 57(5):308-322.
PMID: 31935149 PMC: 7774304. DOI: 10.1080/10408363.2019.1711360.
Effect of fenofibrate on uric acid level in patients with gout.
Jung J, Choi Y, Suh C, Yoon D, Kim H Sci Rep. 2018; 8(1):16767.
PMID: 30425304 PMC: 6233215. DOI: 10.1038/s41598-018-35175-z.