Apolipoprotein A-IV (apoA-IV) is a lipid-binding protein, which is primarily synthesized in the small intestine, packaged into chylomicrons, and secreted into intestinal lymph during fat absorption. In the circulation, apoA-IV is present on chylomicron remnants, high-density lipoproteins, and also in lipid-free form. ApoA-IV is involved in a myriad of physiological processes such as lipid absorption and metabolism, anti-atherosclerosis, platelet aggregation and thrombosis, glucose homeostasis, and food intake. ApoA-IV deficiency is associated with atherosclerosis and diabetes, which renders it as a potential therapeutic target for treatment of these diseases. While much has been learned about the physiological functions of apoA-IV using rodent models, the action of apoA-IV at the cellular and molecular levels is less understood, let alone apoA-IV-interacting partners. In this review, we will summarize the findings on the molecular function of apoA-IV and apoA-IV-interacting proteins. The information will shed light on the discovery of apoA-IV receptors and the understanding of the molecular mechanism underlying its mode of action.

Viroids are circular noncoding RNAs that infect plants. Without encoding any protein, these noncoding RNAs contain the necessary genetic information for propagation in hosts. Nuclear-replicating viroids employ DNA-dependent RNA polymerase II (Pol II) for replication, a process that makes a DNA-dependent enzyme recognize RNA templates. Recently, a splicing variant of transcription factor IIIA (TFIIIA-7ZF) was identified as essential for Pol II to replicate potato spindle tuber viroid (PSTVd). The expression of TFIIIA-7ZF, particularly the splicing event, is regulated by a ribosomal protein (RPL5). PSTVd modulates its expression through a direct interaction with RPL5 resulting in optimized expression of TFIIIA-7ZF. This review summarizes the recent discoveries of host factors and regulatory mechanisms underlying PSTVd-templated transcription processes and raises new questions that may help future exploration in this direction. In addition, it briefly compares the machinery and the regulatory mechanism for PSTVd with the replication/transcription system of human hepatitis delta virus.

Glutamine (Gln) is required for intestinal mucosal homeostasis, and it can promote triglyceride absorption. The intestinal mucosal mast cells (MMCs) are activated during fat absorption. This study investigated the potential role of Gln on fat absorption-induced activation of MMCs in rats. Lymph fistula rats (n = 24) were studied after an overnight recovery with the infusion of saline only, saline plus 85 mM L-glutamine (L-Gln) or 85 mM D-glutamine (D-Gln), respectively. On the test day, rats (n = 8/group) were given an intraduodenal bolus of 20% Intralipid contained either saline only (vehicle group), 85 mM L-Gln (L-Gln group), or 85 mM D-Gln (D-Gln group). Lymph was collected hourly for up to 6 h for analyses. The results showed that intestinal lymph from rats given L-Gln had increased levels of apolipoprotein B (ApoB) and A-I (ApoA-I), concomitant with an increased spectrum of smaller chylomicron particles. Unexpectedly, L-Gln also increased levels of rat mucosal mast cell protease II (RMCPII), as well as histamine and prostaglandin D₂ (PGD₂) in response to dietary lipid. However, these effects were not observed in rats treated with 85 mM of the stereoisomer D-Gln. Our results showed that L-glutamine could specifically activate MMCs to degranulate and release MMC mediators to the lymph during fat absorption. This observation is potentially important clinically since L-glutamine is often used to promote gut health and repair leaky gut.

The sequential meal pattern has recently received more attention because it reflects a phycological diet style for human beings. The present study investigated the effects of the second lipid meal on lymphatic lipid absorption and transport in adult rats following a previous lipid meal. Using the well-established lymph fistula model, we found that the second lipid meal significantly increased the lymphatic output of triglycerides, cholesterol, phospholipids, and non-esterified fatty acids compared with a single lipid meal. Besides that, the time reaching the peak of each lipid output was significantly faster compared with the first lipid meal. Additionally, the second lipid meal significantly increased the lymphatic output of apolipoprotein A-IV (ApoA-IV), but not apolipoprotein B-48 (ApoB-48) or apolipoprotein A-I (ApoA-I). Interestingly, the triglyceride/apoB-48 ratio was significantly increased after the second lipid meal, indicating the increased chylomicron size in the lymph. Finally, the second lipid meal increased the lymphatic output of rat mucosal mast cell protease II (RMCPII). No change was found in the expression of genes related to the permeability of lymphatic lacteals, including vascular endothelial growth factor-A (Vegfa), vascular endothelial growth factor receptor 1 (Flt1), and Neuropilin1 (Nrp1). Collectively, the second lipid meal led to the rapid appearance of bigger-sized chylomicrons in the lymph. It also increased the lymphatic output of various lipids and apoA-IV, and mucosal mast cell activity in the intestine.