Potential Contribution of Short Chain Fatty Acids to Hepatic Apolipoprotein A-I Production

Abstract

Apolipoprotein A-I (ApoA-I) is the major protein of high density lipoprotein (HDL) particles and has a crucial role in reverse cholesterol transport (RCT). It has been postulated that elevating production of de novo ApoA-I might translate into the formation of new functional HDL particles that could lower cardiovascular disease (CVD) risk via RCT. During inflammation, serum ApoA-I concentrations are reduced, which contributes to the development of dysfunctional HDL particles as Serum Amyloid A (SAA) overtakes the position of ApoA-I within the HDL particles. Therefore, instead of elevating serum HDL cholesterol concentrations, rescuing lower serum ApoA-I concentrations could be beneficial in both normal and inflamed conditions. Several nutritional compounds, amongst others short chain fatty acids (SCFAs), have shown their capacity to modulate hepatic lipoprotein metabolism. In this review we provide an overview of HDL and more specific ApoA-I metabolism, SCFAs physiology and the current knowledge regarding the influence of SCFAs on ApoA-I expression and synthesis in human liver cells. We conclude that the current evidence regarding the effect of SCFAs on ApoA-I transcription and secretion is promising, however there is a need to investigate which dietary fibres could lead to increased SCFAs formation and consequent elevated ApoA-I concentrations.

The Mechanism of Probiotics in Preventing the Risk of Hypercholesterolemia

“…Moreover, Tayyeb et al [66] concluded that the enhanced ApoA-I transcription in HepG2 cells was not only by butyrate but also by other SCFAs. However, the increase of ApoA-I secretion in the presence of SCFAs is not found in the human colon adenocarcinoma (Caco-2) cells [62].…”

“…SCFAs are fatty acid hydrocarbon groups comprising C1 until C6 hydrocarbon bones. The members of this group are formic acid (C1), acetic acid (C2), propionic acid (C3), butyric acid (C4), valeric acid (C5), and hexanoic acid (C6) [62]. In the human digestion tract, the majority (95%) of SCFAs found are acetic acid, propionic acid, and butyric acid.…”

“…On the HDL particle, ApoA-I plays an essential role in RCT (reverse cholesterol transport) process as the acceptor of the cholesterol. It is due to its function as a ligand for the ATP-binding cassete transporter A1 (ABCA1) and ATP-binding cassette sub-family G member 1 (ABCG1) [62]. Zhao et al [63] showed that SCFAs administration increases the HDL-C concentration in the serum of the experimental mouse.…”

“…It has been found that the secretion of interleukin 8 (IL-8), a cytokine that activates neutrophils on inflammation reaction, is significantly inhibited by the presence of SCFAs such as propionate, butyrate, and valerate. As for the effect of the antibiotics, amoxicillin has been found to suppress the expression of ApoA-I by lowering PPARα activation on HepG2 cells [62].…”

Gut Microbial-Derived Short Chain Fatty Acids: Impact on Adipose Tissue Physiology

“…In addition to stool, some excretion of SCFAs from the body may occur in urine and breath (~5 to 20%) [ 95 ]. While SCFA have a clear positive impact on the intestinal environment via reduction of colonic pH [ 96 ] and modulation of microbial and colonic energy homeostasis [ 74 , 97 ], SCFAs counteract obesity-induced inflammation [ 98 ] and regulate glucose [ 99 ] and lipid metabolism [ 100 ] ( Figure 2 ). To what extent these effects directly or indirectly control the physiological function of host adipose tissue will be discussed in further sections.…”