Structure-Specific Effects of Short-Chain Fatty Acids on Plasma Cholesterol Concentration in Male Syrian Hamsters

Abstract

Previous studies have shown that short-chain fatty acids (SCFAs) are capable of decreasing plasma cholesterol. However, the relative plasma-cholesterol-lowering activity of individual SCFAs and the underlying mechanisms by which SCFAs decrease plasma cholesterol remain largely unknown. The present study was done to compare the plasma-cholesterol-lowering potencies of four common SCFAs with 2-5 carbons and to investigate their interactions with gene expressions of key regulatory factors involved in cholesterol metabolism. For 6 weeks, five groups of male Golden hamsters were fed either a control high-cholesterol diet (HCD) or one of the four experimental HCDs containing 0.5 mol of acetate (Ac), propionate (Pr), butyrate (Bu), or valerate (Va) per kilogram of the diet. The results showed that Ac, Pr, and Bu significantly reduced plasma total cholesterol (TC) by 24, 18, and 17% (P < 0.05), respectively. All four SCFAs could decrease non-HDL cholesterol (non-HDL-C) and the non-HDL-C/HDL-C ratio. The addition of Ac, Pr, or Bu into the diet significantly promoted fecal excretion of bile acids by 121, 113, or 120% (P < 0.05), respectively, and upregulated the gene expressions of sterol-regulatory-element-binding protein 2 (SREBP2), low-density-lipoprotein receptor (LDLR), and cholesterol 7α-hydroxylase (CYP7A1) in the liver. It was concluded that SCFAs with 2-4 carbons (Ac, Pr, and Bu) are more hypocholesterolemic than Va, which has 5 carbons, via enhancing fecal excretion of bile acids and promoting the hepatic uptake of cholesterol from the blood.

Unraveling Host-Gut Microbiota Dialogue and Its Impact on Cholesterol Levels

“…A similar rise in Cyp7a was observed in Apoe-deficient mice fed with a cholesterolrich diet supplemented with butyrate, with additional beneficial effects on the "reverse cholesterol transport" (RCT) (Du et al, 2019). The connection between SCFAs and BAs metabolism was further reported in Syrian hamsters (Zhao et al, 2017). The addition of acetate, propionate, or butyrate to a cholesterol-rich diet resulted in decreased CT levels and LDL-C/HDL-C ratio and to increased fecal excretion of BAs (LCA, DCA, CDCA, CA).…”

“…Ex vivo and in vivo studies have shown that acetate and butyrate (but not propionate) are potential precursors of cholesterol synthesis that can be incorporated into the endogenous cholesterol synthesis pathway (Wolever et al, 1991;Demigné et al, 1995;den Besten et al, 2013). By contrast, earlier studies reported inhibition of cholesterol synthesis by propionate through decreased expression of the HMGCS and HMGCR genes (Bush and Milligan, 1971;Rodwell et al, 1976;Demigné et al, 1995), white more recent studies have not confirmed such effects (Zhao et al, 2017). Accordingly, in healthy subjects, the oral administration of propionate does not lower plasma cholesterol but does increase HDL and triglycerides levels (Venter et al, 1990).…”

“…The addition of acetate, propionate, or butyrate to a cholesterol-rich diet resulted in decreased CT levels and LDL-C/HDL-C ratio and to increased fecal excretion of BAs (LCA, DCA, CDCA, CA). Expression of the SREBP2, LDLR, and CYP7A1 genes was also involved (Zhao et al, 2017). The effects of SCFAs were more specifically addressed in mice deficient for FFAR2/GPR43, one of the SCFA receptors (Bjursell et al, 2011).…”

Two Weeks Of Western Diet Disrupts Liver Molecular Markers Of Cholesterol Metabolism In Rat

“…However, this association does not hold for the HFD-fed animals since ABCG5/G8 mRNA levels were increased in these groups of rats. It is likely that other mechanisms such as fecal excretion of biliary acids (27) or increased synthesis and secretion of VLDL are involved Other important questions that emerge from the present results are what factors alter the expression of key metabolic markers of hepatic cholesterol homeostasis in response to 2 weeks of WD, and why does the response in animals submitted to the HFD not reach the same extent? It must be taken into account that after 2 weeks, hepatic TG levels were higher in WD-than in HFD-fed rats, and this might have interfered with cholesterol metabolism.…”

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

“…However, this association does not hold for the HFD-fed animals since ABCG5/G8 mRNA levels were increased in these groups of rats. It is likely that other mechanisms such as fecal excretion of biliary acids [27] or increased synthesis and secretion of VLDL are involved.…”