Two weeks of western diet disrupts liver molecular markers of cholesterol metabolism in rats.

Autor: St-Amand R; École de Kinésiologie et des Sciences de l'Activité Physique, Faculté de Médecine, Université de Montréal, Montréal, Canada., Ngo Sock ÉT; École de Kinésiologie et des Sciences de l'Activité Physique, Faculté de Médecine, Université de Montréal, Montréal, Canada., Quinn S; Department of Exercise Sciences, Université du Québec à Montréal, 141, Avenue Président-Kennedy, C.P. 8888, succursale Centre-Ville, Montréal, Québec, H3C 3P8, Canada., Lavoie JM; École de Kinésiologie et des Sciences de l'Activité Physique, Faculté de Médecine, Université de Montréal, Montréal, Canada., St-Pierre DH; Department of Exercise Sciences, Université du Québec à Montréal, 141, Avenue Président-Kennedy, C.P. 8888, succursale Centre-Ville, Montréal, Québec, H3C 3P8, Canada. david.stpierre.uqam@gmail.com.
Jazyk: angličtina
Zdroj: Lipids in health and disease [Lipids Health Dis] 2020 Aug 21; Vol. 19 (1), pp. 192. Date of Electronic Publication: 2020 Aug 21.
DOI: 10.1186/s12944-020-01351-2
Abstrakt: Background: The present study was designed to test the hypothesis that in the liver, excessive fat accumulation impairs cholesterol metabolism mainly by altering the low-density lipoprotein-receptor (LDL-R) pathway.
Method: Young male Wistar rats were fed standard (SD), high fat (HFD; 60% kcal) or Western (WD; 40% fat + 35% sucrose (17.5% fructose)) diets for 2 or 6 weeks.
Results: Weight gain (~ 40 g) was observed only following 6 weeks of the obesogenic diets (P < 0.01). Compared to the 2-week treatment, obesogenic diets tripled fat pad weight (~ 20 vs 7 g) after 6 weeks. Hepatic triglyceride (TG) levels were greater in response to both the WD and HFD compared to the SD (P < 0.01) at 2 and 6 weeks and their concentrations were greater (P < 0.05) in WD than HFD at 2 weeks. Plasma total cholesterol levels were higher (P < 0.05) in animals submitted to WD. After 2 and 6 weeks, liver expression of LDL-R, proprotein convertase subtilisin/kexin 9 (PCSKk9) and sterol regulatory element binding protein 2 (SREBP2), involved in LDL-cholesterol uptake, was lower in animals submitted to WD than in others treated with HFD or SD (P < 0.01). Similarly, low-density lipoprotein-receptor-related protein 1 (LRP1) and acyl-CoA cholesterol acyltransferase-2 (ACAT-2) mRNA levels were lower (P < 0.01) among WD compared to SD-fed rats. Expression of the gene coding the main regulator of endogenous cholesterol synthesis, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoAR) was reduced in response to WD compared to SD and HFD at 2 (P < 0.001) and 6 (P < 0.05) weeks. Being enriched in fructose, the WD strongly promoted the expression of carbohydrate-response element binding protein (ChREBP) and acetyl-CoA carboxylase (ACC), two key regulators of de novo lipogenesis.
Conclusion: These results show that the WD promptly increased TG levels in the liver by potentiating fat storage. This impaired the pathway of hepatic cholesterol uptake via the LDL-R axis, promoting a rapid increase in plasma total cholesterol levels. These results indicate that liver fat content is a factor involved in the regulation of plasma cholesterol.
Databáze: MEDLINE
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