Modulation of lipid synthesis, apolipoprotein biogenesis, and lipoprotein assembly by butyrate

Abstract

Short-chain fatty acids (SCFAs) are potent modulators of the growth, function, and differentiation of intestinal epithelia. In addition, high-fiber diets may protect against the development of atherosclerosis because of their cholesterol-lowering effects due, in large part, to SCFA production, liver sterol metabolism, and bile acid excretion. Although the small gut plays a major role in dietary fat transport and contributes substantially to plasma cholesterol and lipoprotein homeostasis, the impact of SCFAs on intestinal lipid handling remains unknown. In the present study, the modulation of lipid synthesis, apolipoprotein biogenesis, and lipoprotein secretion by butyrate was investigated in Caco-2 cells plated on permeable polycarbonate filters, which permit separate access to the upper and lower compartments of the monolayers. Highly differentiated and polarized cells (20 days of culture) were incubated for 20 h with 20 mM butyrate in the apical medium. In the presence of [14C]oleic acid, butyrate led to a significant reduction of secreted, labeled triglycerides (27%; P < 0.01) and phospholipids (25%; P < 0.05). Similarly, butyrate significantly decreased the incorporation of [14C]acetate into exported cholesteryl ester (49%; P < 0.005). As expected from these results, with [14C]oleic acid as a precursor, butyrate significantly (P < 0.05) diminished the delivery of radiolabeled chylomicrons and very low-density lipoproteins. In parallel, [35S]methionine pulse labeling of Caco-2 cells revealed the concomitant inhibitory effect of butyrate on the synthesis of apolipoproteins B-48 (28%; P < 0.05) and A-I (32%; P < 0.01). Collectively, our data indicate that butyrate may influence lipid metabolism in Caco-2 cells, thus suggesting a potential regulation of intestinal fat absorption and circulating lipoprotein concentrations.

Modification in Oxidative Stress, Inflammation, and Lipoprotein Assembly in Response to Hepatocyte Nuclear Factor 4α Knockdown in Intestinal Epithelial Cells

“…The synthesis and secretion of apolipoproteins (A-I, A-IV, B-48, B-100, and E) was assessed as described previously (40). To first induce apolipoprotein synthesis, cells were incubated apically with unlabeled oleic acid bound to albumin in serumfree medium for 24 h before […”

Localization and role of NPC1L1 in cholesterol absorption in human intestine

“…For individual experiments, cells were plated at a density of 1 3 10 6 cells/well on 24.5 mm polycarbonate Transwell filter inserts with 0.4 mm pores (Costar, Cambridge, MA) in DMEM (as described above) supplemented with 5% FBS. The inserts were placed onto six-well culture plates and cultured for 20 days, at which time Caco-2 cells are highly differentiated and appropriate for lipid metabolism (23,24).…”

Effect of gala apples (Malus domestica Borkh) on lipidemia of hyperlipidemic rats

“…These supplements led to a reduction of blood and liver cholesterol, since soluble fibers have properties that hinder the absorption of nutrients and cholesterol, thus causing a higher level of cholesterol in the feces (DE ANGELIS, 2001;MARCIL et al, 2002).…”