Guar gum and similar soluble fibers in the regulation of cholesterol metabolism: current understandings and future research priorities

Abstract

The hypocholesterolemic effects associated with soluble fiber consumption are clear from animal model and human clinical investigations. Moreover, the modulation of whole-body cholesterol metabolism in response to dietary fiber consumption, including intestinal cholesterol absorption and fecal sterol and bile acid loss, has been the subject of many published reports. However, our understanding of how dietary fibers regulate molecular events at the gene/protein level and alter cellular cholesterol metabolism is limited. The modern emphasis on molecular nutrition and rapid progress in 'high-dimensional' biological techniques will permit further explorations of the role of genetic polymorphisms in determining the variable interindividual responses to soluble fibers. Furthermore, with traditional molecular biology tools and the application of 'omic' technology, specific insight into how fibers modulate the expression of genes and proteins that regulate intestinal cholesterol absorption and alter hepatic sterol balance will be gained. Detailed knowledge of the molecular mechanisms by which soluble fibers reduce plasma cholesterol concentrations is paramount to developing novel fiber-based "cocktails" that target specific metabolic pathways to gain maximal cholesterol reductions.

Keywords: bile acids; cholesterol; dietary fiber; gene; protein.

Figure 1

Potential mechanisms responsible for the hypocholesterolemic effects associated with the consumption of soluble fibers. Copyright © 2007. Adapted with permission from Rideout TC, Yuan Z, Bakovic M, et al. 2007. Guar gum consumption increases hepatic nuclear SREBP2 and LDL receptor expression in pigs fed an atherogenic diet. J Nutr, 137:568–72. Abbreviations: ABCG5/G8, ATP-binding cassette transporter G5 and G8; C, cholesterol; CE, cholesteryl ester; CYP7A, cholesterol 7a-hydroxylase; GG, guar gum; LDLr, low-density lipoprotein receptor; NPC1L1, Niemann-Pick-C-1 like 1; SCFA, short-chain fatty acids; SREBP2, sterol regulatory element binding protein 2.

Figure 2

Major pathways involved in regulating the enterohepatic circulation of cholesterol. Copyright © 2007. Adapted with permission from Rideout TC, Yuan Z, Bakovic M, et al. 2007. Guar gum consumption increases hepatic nuclear SREBP2 and LDL receptor expression in pigs fed an atherogenic diet. J Nutr, 137:568–72. Abbreviations: ABCG5, ATP-binding cassette transporter G5; ABCG8, ATP-binding cassette transporter G5; ACAT, acyl-coenzyme A:cholesterol acyltransferase; ASBT, apical sodium-dependent bile acid transporter; C, cholesterol; CE, cholesteryl ester; CEL, carboxyl ester lipase; CYP7A, cholesterol 7α-hydroxylase; HDL, high-density lipoprotein; ABCA1, ATP-binding cassette transporter A1; HMG-CoAr, 3-hydroxy-3-methylglutaryl-CoA reductase; LDLr, low-density lipoprotein receptor; NPC1L1, Niemann-Pick-C-1 like 1; SR-B1, scavenger receptor class B, type 1; VLDL, very-low density lipoprotein.