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(1) Background: Nutritional strategies to enhance gut function and reduce the piglet diarrhea rate are critical to increase the growth performance of piglets. The purpose of this study was to investigate whether dietary fat types and/or fat microencapsulation techniques are involved in regulating the fatty acid transport system and the mechanical and immunological barriers of the small intestine. (2) Methods: Three hundred twenty-four weaning piglets were randomly divided into three groups fed a soybean oil diet (SBO, control group, 6.0% soybean oil), palm oil diet (PO, 6.0% palm oil), or encapsulated palm oil diet (EPO, 7.5% encapsulated palm oil). (3) Results: A significantly lower mRNA expression of the claudin was observed in the duodenum and jejunum of the PO group than in the SBO group ( p &lt; 0.05). However, the mRNA expression and protein abundance of claudin and ZO-1 in the jejunum of the EPO group were higher ( p &lt; 0.05) than in the PO group. Porcine β-defensin (pBD) secretion was not significantly different between the SBO and PO groups ( p &gt; 0.05), while the pBD-2 levels were significantly different ( p &lt; 0.05). Compared with the PO group, the EPO group exhibited a significantly increased secretion of pBD-2 and pBD-129 in the small intestine ( p &lt; 0.05) and pBD-1 in the jejunum and ileum ( p &lt; 0.05). The protein abundances of apolipoprotein AIV (Apo AIV) and intestinal fatty acid binding protein (I-FABP) were significantly lower in the PO group than in the SBO group ( p &lt; 0.05). Simultaneously, the protein abundances of fatty acid transport protein 4 (FATP4), fatty acid translocase (CD36), and I-FABP were higher in the EPO group than in the PO group. Furthermore, the low digestibility of palm oil (PO group) might negatively regulate intestinal tight junctions, fatty acid transporters, lipoproteins, and β-defensin through the activation of the AMPK/mTORC1 and AMPK/Sirt1/NF-κB pathways. (4) Conclusions: In summary, microencapsulation techniques might alleviate the negative effects of palm oil and help to improve the intestinal fatty acid transport system and barrier function.

Fat Encapsulation Reduces Diarrhea in Piglets Partially by Repairing the Intestinal Barrier and Improving Fatty Acid Transport