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We compared endogenous ω-3 PUFA production to supplementation for improving obesity-related metabolic dysfunction. Fat-1 transgenic mice, who endogenously convert exogenous ω-6 to ω-3 PUFA, and wild-type littermates were fed a high-fat diet and a daily dose of either ω-3 or ω-6 PUFA-rich oil for 12 wk. The endogenous ω-3 PUFA production improved glucose intolerance and insulin resistance but not hepatic steatosis. Conversely, ω-3 PUFA supplementation fully prevented hepatic steatosis but failed to improve insulin resistance. Both models increased hepatic levels of ω-3 PUFA-containing 2-monoacylglycerol and N-acylethanolamine congeners, and reduced levels of ω-6 PUFA-derived endocannabinoids with ω-3 PUFA supplementation being more efficacious. Reduced hepatic lipid accumulation associated with the endocannabinoidome metabolites EPEA and DHEA, which was causally demonstrated by lower lipid accumulation in oleic acid-treated hepatic cells treated with these metabolites. While both models induced a significant fecal enrichment of the beneficial Allobaculum genus, mice supplemented with ω-3 PUFA displayed additional changes in the gut microbiota functions with a significant reduction of fecal levels of the proinflammatory molecules lipopolysaccharide and flagellin. Multiple-factor analysis identify that the metabolic improvements induced by ω-3 PUFAs were accompanied by a reduced production of the proinflammatory cytokine TNFα, and that ω-3 PUFA supplementation had a stronger effect on improving the hepatic fatty acid profile than endogenous ω-3 PUFA. While endogenous ω-3 PUFA production preferably improves glucose tolerance and insulin resistance, ω-3 PUFA intake appears to be required to elicit selective changes in hepatic endocannabinoidome signaling that are essential to alleviate high-fat diet-induced hepatic steatosis. [ABSTRACT FROM AUTHOR]

Dietary vitamin A and its active metabolites are essential nutrients for many functions as well as potent regulators of gene transcription and growth. Although the epithelium of the small intestine is characterized by rapid and constant renewal and enterocytes play a central role in the absorption and metabolism of alimentary retinol, very little is known about the function of retinoids in the human gastrointestinal epithelium and mechanisms by which programs engage the cell cycle are poorly understood. We have assessed the effects of 10 [micro]M 9- and 13-cisretinoic acid (RA) on proliferation and differentiation processes, lipid esterification, apolipoprotein (apo) biogenesis and lipoprotein secretion along with nuclear factor gene transcription. Treatment of Caco-2 cells with RA at different concentrations and incubation periods revealed the reduction of thymidine incorporation in 60% preconfluent or 100% confluent cells. Concomitantly, RA 1) modulated D-type cyclins by reducing the mitogen-sensitive cyclin D 1 and upregulating cyclin D3 expressions and 2) caused a trend of increase in p38 MAPK, which triggers CDX2, a central protein in cell differentiation. RA remained without effect on lipoprotein output and apo synthesis, even for apo A-I that possesses RARE in its promoter. RA, in combination with 22-hydroxycholesterol, could induce apo A-I gene expression without any impact on apo A-I mass. Only the gene expression of peroxisome proliferator-activated receptor (PPAR)[beta], retinoic receptor (RAR)[beta], and RAR[gamma] was augmented and no alteration was noted in PPAR[alpha], PPAR[gamma], liver X receptor (LXR)[alpha], LXR[beta], and retinoid X receptors. Taken together, these data highlight RA-induced cell differentiation via specific signaling without a significant impact on apo A-I synthesis. retinoids; apolipoproteins; lipoproteins; nuclear factors; lipids

Recently, the idea was advanced that short-chain fatty acids (SCFA) may potentially regulate intestinal fat absorption. The aim of this investigation was to examine the effects of butyrate on the intracellular events governing the assembly of triglyceride-lipoproteins in enterocytes. To this end, differentiated human Caco-2 cells were exposed to 10 or 20 mmol/L butyrate for 20 h. The incubation of Caco-2 cells with butyrate decreased cholesteryl ester (P < 0.005) export in the basolateral medium, probably due to reduced activity of DL-3-hydroxy-3-methyl-glutaryl-CoA reductase (P < 0.02), the rate-limiting enzyme in cholesterol synthesis. Furthermore, a drop was noted in the protein expression of microsomal triglyceride transfer protein (P < 0.03), concomitant with the inhibition of de novo apolipoprotein B-48 synthesis (P < 0.02) and triglyceride-rich lipoprotein output (P < 0.03). Our results support the hypothesis that SCFA can influence lipoprotein concentrations by limiting lipid release from the small intestine into the circulation. KEY WORDS: * HMG-CoA reductase * apolipoprotein B-48 * microsomal triglyceride transfer protein * fat absorption

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 [[sup.14]C]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 [[sup.14]C]acetate into exported cholesteryl ester (49%; P < 0.005). As expected from these results, with [[sup.14]C]oleic acid as a precursor, butyrate significantly (P < 0.05) diminished the delivery of radiolabeled chylomicrons and very low-density lipoproteins. In parallel, [[sup.35]S]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. lipid esterification; cholesterol synthesis; phospholipid; chylomicron; very low-density lipoprotein; apolipoprotein A-I; apolipoprotein B

A pilot study was conducted to estimate the effects of a breast milk expression education and support intervention on breast milk production outcomes in mothers of very and extremely preterm infants. Forty mothers of hospitalized preterm infants (<30 weeks of gestation) were randomized to the experimental intervention or standard care for 6 weeks. Duration and frequency of breast milk expressions and volume of expressed breast milk were measured daily. Samples of breast milk were collected thrice during the study and analyzed for their lipid concentration. Mothers in the experimental group had a statistically significant higher duration of breast milk expression in min/day (p = .043). Differences observed between the two groups regarding the frequency of breast milk expression, volume of breast milk, and lipid concentration were not statistically significant. Results suggest that the experimental intervention may promote breast milk production in mothers of very and extremely preterm infants. [ABSTRACT FROM AUTHOR]

Cranberry fruit has been reported to have high antioxidant effectiveness that is potentially linked to its richness in diversified polyphenolic content. The aim of the present study was to determine the role of cranberry polyphenolic fractions in oxidative stress (OxS), inflammation and mitochondrial functions using intestinal Caco-2/15 cells. The combination of HPLC and UltraPerformance LC®-tandem quadrupole (UPLC-TQD) techniques allowed us to characterize the profile of low, medium and high molecular mass polyphenolic compounds in cranberry extracts. The medium molecular mass fraction was enriched with flavonoids and procyanidin dimers whereas procyanidin oligomers (DP > 4) were the dominant class of polyphenols in the high molecular mass fraction. Pre-incubation of Caco-2/15 cells with these cranberry extracts prevented iron/ascorbate-mediated lipid peroxidation and counteracted lipopolysaccharide-mediated inflammation as evidenced by the decrease in pro-inflammatory cytokines (TNF-a and interleukin-6), cyclo-oxygenase-2 and prostaglandin E2. Cranberry polyphenols (CP) fractions limited both nuclear factor KB activation and Nrf2 down-regulation. Consistently, cranberry procyanidins alleviated OxS-dependent mitochondrial dysfunctions as shown by the rise in ATP production and the up-regulation of Bcl-2, as well as the decline of protein expression of cytochrome c and apoptotic-inducing factor. These mitochondrial effects were associated with a significant stimulation of peroxisome-proliferator-activated receptor y co-activator-1-a, a central inducing factor of mitochondrial biogenesis and transcriptional co-activator of numerous downstream mediators. Finally, cranberry procyanidins forestalled the effect of iron/ascorbate on the protein expression of mitochondrial transcription factors (mtTFA, mtTFB1, mtTFB2). Our findings provide evidence for the capacity of CP to reduce intestinal OxS and inflammation while improving mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]