Modulation of Bile Acid Metabolism to Improve Plasma Lipid and Lipoprotein Profiles

Abstract

New drugs targeting bile acid metabolism are currently being evaluated in clinical studies for their potential to treat cholestatic liver diseases, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Changes in bile acid metabolism, however, translate into an alteration of plasma cholesterol and triglyceride concentrations, which may also affect cardiovascular outcomes in such patients. This review attempts to gain insight into this matter and improve our understanding of the interactions between bile acid and lipid metabolism. Bile acid sequestrants (BAS), which bind bile acids in the intestine and promote their faecal excretion, have long been used in the clinic to reduce LDL cholesterol and, thereby, atherosclerotic cardiovascular disease (ASCVD) risk. However, BAS modestly but consistently increase plasma triglycerides, which is considered a causal risk factor for ASCVD. Like BAS, inhibitors of the apical sodium-dependent bile acid transporter (ASBTi’s) reduce intestinal bile acid absorption. ASBTi’s show effects that are quite similar to those obtained with BAS, which is anticipated when considering that accelerated faecal loss of bile acids is compensated by an increased hepatic synthesis of bile acids from cholesterol. Oppositely, treatment with farnesoid X receptor agonists, resulting in inhibition of bile acid synthesis, appears to be associated with increased LDL cholesterol. In conclusion, the increasing efforts to employ drugs that intervene in bile acid metabolism and signalling pathways for the treatment of metabolic diseases such as NAFLD warrants reinforcing interactions between the bile acid and lipid and lipoprotein research fields. This review may be considered as the first step in this process.

Effects of Bile Acid Modulation by Dietary Fat, Cholecystectomy, and Bile Acid Sequestrant on Energy, Glucose, and Lipid Metabolism and Gut Microbiota in Mice

“…BAS mainly lowers LDL cholesterol between 15% and 30% and slightly increases serum HDL concentrations by 3–5% [ 28 ]. However, their effect on serum triglyceride concentrations remains controversial [ 10 ].…”

Hepatocellular carcinoma: Novel understandings and therapeutic strategies based on bile acids (Review)

“…In humans, the classical pathway of BA synthesis accounts for at least 75% of total BA production and is considered to be the main pathway of BA biosynthesis (10). Primary BAs are amino-conjugated at the carboxyl group, with a ratio of glycine to taurine conjugates of approximately 3:1 (11). BAs may also bind to sulfate or glucuronic acid to form fully ionized, negatively charged hydrophilic polar molecules, and these bound forms of BAs subsequently discharge into the intestine with bile.…”

“…BAs have a variety of physiological roles, the most important of which is to promote the digestion and absorption of lipids (11). BA molecules have hydrophilic and hydrophobic sides in their configuration, which endows them with strong interfacial activity to reduce the surface tension between oil and water phases and promote lipid emulsification.…”

“…BA molecules have hydrophilic and hydrophobic sides in their configuration, which endows them with strong interfacial activity to reduce the surface tension between oil and water phases and promote lipid emulsification. At the same time, BAs enlarge the contact surface between lipids and lipase and accelerate the digestion of lipids (11,24). BAs may also inhibit the precipitation of cholesterol in bile and prevent the formation of cholesterol stones.…”

Determination of angiotensin-converting enzyme concentration in cardiovascular patients

“…This is supported byZhou et al, (2018), who published the significant rise in CVDs patients, whereasLiu et al, (2015) reported no significant difference between both groups.The results of the present study indicated that high level of triglyceride was found in the serum of patients and significantly more than in control < (p = 0.0001) , Results by Talayero & Sacks,(2011) andAberra et al, (2020) reached to the same conclusion, but Sun,(2021) found no significant difference in the level of TG between CVDs patients and healthy individuals. Although cholesterol plays a fundamental role in a plethora of intracellular mechanisms, it is known that individuals with highplasma cholesterol concentration are at increased risk of atherosclerotic heart disease(Zhang et al,2021) . We found significant increase in blood cholesterol of CVDs patients compared to its level in control (p = 0.0001).…”