Possible Role of Fatty Acids in Milk as the Regulator of the Expression of Cytosolic Binding Proteins for Fatty Acids and Vitamin A through PPAR.ALPHA. in Developing Rats

Abstract

Summary Fatty acids in milk are thought to play an important role in intestinal maturation and gene expression in the postnatal small intestine. In this study, we determined the jejunal mRNA levels, in rats, of peroxisome proliferator-activated receptor ␣ (PPAR ␣ ) and PPAR ␦ which are nuclear receptors for fatty acids. We also measured expression of their target genes during the postnatal period, namely liver type fatty acid-binding protein (L-FABP) and cellular retinol-binding protein, type II (CRBPII). The mRNA levels of PPAR ␣ , L-FABP and CRBPII, but not PPAR ␦ , gradually increased during the suckling period and then sharply declined to a low level at the end of the weaning period. Rat pups at 17 d of age, weaned to a high-fat diet, showed significantly greater mRNA levels of PPAR ␣ , L-FABP and CRBPII than those weaned to a low-fat diet. Oral administration of PPAR ␣ ligand, WY14,643 during four consecutive days of the weanling period caused a parallel increase in the mRNA levels of PPAR ␣ , L-FABP and CRBPII genes. Furthermore, caprylic acid and oleic acid, which are major components of fatty acids in milk, induced jejunal PPAR ␣ , L-FABP and CRBPII gene expression. Our results suggest that fatty acids in milk may play a pivotal role in maintaining an enhanced level of expression of L-FABP and CRBPII genes in the small intestine, presumably by acting as inducers of PPAR ␣ gene expression.

Time-resolved Quantitative Proteome Analysis of In Vivo Intestinal Development

“…The two major isoforms of FABP found in enterocytes, intestinal-type (I-FABP) and liver-type (L-FABP), are known to have different binding specificity and their mRNA levels have previously been studied in rats during postnatal intestinal development. I-FABP mRNA levels remain constant during the suckling period, whereas the mRNA levels of L-FABP gradually increase during the suckling period and then sharply declines at the end of weaning (17,20). We identified both isoforms, which showed different expression profiles in comparison to the mentioned previous studies (Table I).…”

Gene Expression Changes in the Jejunum of Rats during the Transient Suckling-Weaning Period

“…Slc27a2 plays a key role in ␤-oxidation (44). Higher expression of Slc27a2 during the suckling period in the jejunum may be important for energy generation from fat because milk contains large amounts of fat and our previous studies showed that the gene expressions of rate-controlling enzymes of ␤-oxidation, such as acyl-CoA oxidase, are highly expressed during the suckling-weaning period (6,7). We also detected the zinc transporter Slc30a2 (45) among the downregulated genes.…”

“…It is necessary in further studies to examine whether these transcriptional factors regulate the genes downregulated during the sucklingweaning period. Our recent studies indicated that the expressions of genes related to dietary fat absorption and ␤-oxidation in the rat small intestine during suckling are enhanced by dietary fat in milk through activation of the nuclear receptor PPAR␣, which directly binds fatty acids as ligands (6,7). Another recent study revealed that Slc27a2 in the mouse small intestine is induced by PPAR␣ (49).…”

“…In addition, we previously reported that the gene expressions of liver-type fatty acid-binding protein [L-FABP ( Fabp1 )] and cellular retinol-binding protein type II [CRBPII ( Rbp2 )], which are involved in transporting fatty acids and vitamin A, respectively, from the lumen to enterocytes, as well as a ␤ -oxidation rate-controlling gene [acyl-CoA oxidase ( Acox1 )], were highly expressed in the transient suckling-weaning period, and declined after weaning ( 6 , 7 ). Furthermore, the gene expression of peroxisome proliferator-activated receptor ␣ [PPAR ␣ ( Ppara )], a transcriptional factor for these genes, was associated with these gene expression changes ( 6 ).…”

Induction of the BCMO1 Gene during the Suckling-Weaning Transition in Rats Is Associated with Histone H3 K4 Methylation and Subsequent Coactivator Binding and Histone H3 Acetylation to the Gene

“…Previous studies have also demonstrated that jejunal expression of genes related to nutrient absorption such as cellular retinol-binding protein, type II (CRBPII) and liver-type fatty-acid binding protein (L-FABP) are regulated by another subtype of PPAR, i.e., PPAR␣ (35). During the postnatal period, the PPAR␣ gene is highly expressed during the suckling-weaning transient period from 13 to 20 d after birth (36). Thus, PPAR␣ may be also concerned with the induction of the jejunal BCMO1 gene confi ned to the period between days 13 and 20 after birth.…”