Lipid metabolic diseases have substantial morbidity and mortality rates, posing a significant threat to human health. PPARα, a member of the peroxisome proliferator-activated receptors (PPARs), plays a crucial role in lipid metabolism and immune regulation. Recent studies have increasingly recognized the pivotal involvement of PPARα in diverse pathological conditions. This comprehensive review aims to elucidate the multifaceted role of PPARα in metabolic diseases including liver diseases, diabetes-related diseases, age-related diseases, and cancers, shedding light on the underlying molecular mechanisms and some regulatory effects of natural/synthetic ligands of PPARα. By summarizing the latest research findings on PPARα, we aim to provide a foundation for the possible therapeutic exploitation of PPARα in lipid metabolic diseases.

Antibiotics are widely used as growth promoters (AGPs) in livestock production to improve animal performance and health. However, pig producers today face the prohibition of in-feed antimicrobials and have to find safe and effective alternatives. Lactobacillus species are active microorganisms that convey multiple beneficial effects to the host and are one of the most promising AGPs replacements. Here, we aim to comprehensively assess the effects of Lactobacillus spp. supplementation on growth performance and intestinal morphology (villus height [VH], crypt depth [CD], and the V/C ratio) of piglets. Among the 196 identified studies, 20 met the criteria and were included in the meta-analysis. The effects of Lactobacillus-based probiotics supplementation on growth performance and intestinal morphology were analyzed using a random-effects model. And the publication bias was evaluated by funnel plots. Our results revealed that Lactobacillus spp. supplementation significantly improved the growth performance, including average daily feed intake (ADFI), average daily gain (ADG), and the gain-to-feed ratio (G/F) in piglets (P < 0.05). Meanwhile, Lactobacillus spp. remarkably increased VH and the V/C ratio (P < 0.05) in the small intestine, including the duodenum, jejunum, and ileum, which might contribute to an improved digestive capacity of these animals. In conclusion, our findings provide concrete evidence of the growth-promoting effects of Lactobacillus spp. supplementation in piglets and a better understanding of the potential of Lactobacillus-based probiotics as AGPs alternatives in pig production.

Inflammatory bowel disease (IBD), a chronic inflammatory disorder of the gastrointestinal tract, is frequently complicated by extraintestinal manifestations such as functional hyposplenism. Increasing evidence highlights its pathogenesis as a multifactorial interplay of gut dysbiosis, intestinal barrier dysfunction, and dysregulated immune responses. While probiotics, particularly Lactobacillus spp., have emerged as potential therapeutics for IBD, restoring intestinal homeostasis, their systemic immunomodulatory effects remain underexplored. Here, we investigated the protective role of Lactobacillus johnsonii N5 in DSS-induced colitis, focusing on inflammation inhibition and splenic T cell regulation. Pretreatment with L. johnsonii N5 significantly attenuated colitis severity, as evidenced by preserved body weight, reduced disease activity index, and prevention of colon shortening. N5 suppressed colonic pro-inflammatory factors such as TNF-α, Il-1b, Il-6, and CXCL1, while elevating anti-inflammatory IL-10 at both mRNA and protein levels. Transcriptomic analysis of the spleen revealed that N5 mediated the downregulation of inflammatory pathways, including the IL-17 and TNF signaling pathways, as well as the HIF-1 signaling pathway, and modulated the metabolic pathway of oxidative phosphorylation. Flow cytometry analysis demonstrated that N5 rebalanced splenic Treg/Th17 responses by expanding the Treg population and reducing the production of IL-17A in Th17 cells. Notably, Th17-associated IL-17A positively correlated with intestinal pro-inflammatory mediators, emphasizing the role of Th17 cells in driving colitis. In contrast, splenic Treg abundance positively correlated with colonic IL-10 levels, suggesting a link between systemic immune regulation and intestinal anti-inflammatory responses. Our study underscores the therapeutic potential of targeting gut–immune crosstalk through probiotics, thereby offering valuable insights for developing live bacterial-based interventions for IBD and other inflammatory disorders.

Deoxynivalenol (DON) is among the most prevalent contaminants in cereal crops and has been demonstrated to impair male spermatogenesis and induce oxidative stress, testicular apoptosis, and disruption of the blood–testis barrier (BTB). Lactoferrin (LF) is an iron-binding glycoprotein with multifunctions including anti-inflammation and antioxidation. Thus, this study aimed to investigate the effects of LF on the spermatogenesis and integrity of the BTB in DON-exposed mice. Thirty-two male mice were allotted to four groups for a 35-day feeding period: vehicle (basal diet), DON (12 mg/kg), LF (10 mg/d, p.o.), and DON + LF. The results showed that DON induced vacuolization of the spermatogenic epithelium, broke the adhesion junction between Sertoli cells and spermatids established by N-cadherin and induced testicular oxidative stress. LF administration restored sperm production, attenuated the DON-induced oxidative stress and reduced the breakages in adhesion junction. DON exposure enhanced the protein expression of occludin. Transcriptional profiling of the testis observed a disturbance in the expression profiles of cell adhesion and inflammatory response genes, and LF administration reversed these gene expressions. Furthermore, down-regulated signaling pathways, including the apical junction, TNFα signaling via NF-κB, and TGF-β in the DON group were observed. These were restored by LF. Enrichment analysis between DON + LF group and vehicle also confirmed the absence of these pathways. These findings indicated that LF eliminated the DON-induced detriment to spermatogenesis and cell connections between Sertoli cells and spermatids via improving antioxidant capacity and modifying the inflammatory response and cell adhesion genes.

As a member of alpha-coronaviruses, PEDV could lead to severe diarrhea and dehydration in newborn piglets. Given that lipid peroxides in the liver are key mediators of cell proliferation and death, the role and regulation of endogenous lipid peroxide metabolism in response to coronavirus infection need to be illuminated. The enzymatic activities of SOD, CAT, mitochondrial complex-I, complex-III, and complex-V, along with the glutathione and ATP contents, were significantly decreased in the liver of PEDV piglets. In contrast, the lipid peroxidation biomarkers, malondialdehyde, and ROS were markedly elevated. Moreover, we found that the peroxisome metabolism was inhibited by the PEDV infection using transcriptome analysis. These down-regulated anti-oxidative genes, including GPX4, CAT, SOD1, SOD2, GCLC, and SLC7A11, were further validated by qRT-PCR and immunoblotting. Because the nuclear receptor RORγ-driven MVA pathway is critical for LPO, we provided new evidence that RORγ also controlled the genes CAT and GPX4 involved in peroxisome metabolism in the PEDV piglets. We found that RORγ directly binds to these two genes using ChIP-seq and ChIP-qPCR analysis, where PEDV strongly repressed the binding enrichments. The occupancies of histone active marks such as H3K9/27ac and H3K4me1/2, together with active co-factor p300 and polymerase II at the locus of CAT and GPX4, were significantly decreased. Importantly, PEDV infection disrupted the physical association between RORγ and NRF2, facilitating the down-regulation of the CAT and GPX4 genes at the transcriptional levels. RORγ is a potential factor in modulating the CAT and GPX4 gene expressions in the liver of PEDV piglets by interacting with NRF2 and histone modifications.

Deoxynivalenol (DON) is a secondary metabolite of fungi. Ingestion of feed containing DON causes severe intestinal damage in humans and animals, possibly due to cholesterol-enriched lipid raft abnormalities. Cholic acid (CA) and lithocholic acid (LCA) are metabolites of cholesterol transformation, which have been proven to benefit epithelial cell proliferation and reduce intestinal inflammation and lesions. Therefore, we aimed to study the protective roles of CA and LCA administration on the DON-exposed intestinal epithelial cells (IPI-2I) and the underlying mechanisms involved in cholesterol metabolism. We found that LCA pretreatment, but not CA, alleviated the reduction of cell numbers caused by DON exposure. Furthermore, we demonstrate that LCA restored the DON-induced cell apoptosis by reducing the cleaved caspase 3 and cleaved PARP-1 expression. DON-increased cellular cholesterol and bile acid contents were significantly reduced when LCA was co-treated. Further transcriptomic analysis revealed that the aberrant cholesterol homeostasis genes profile was observed in the cells exposed to DON or pretreated with LCA. We also validated that the key genes involved in cholesterol biosynthesis and transformation (cholesterol to bile acids) were strongly inhibited by the LCA treatment in the DON-exposed cells. Together, this study demonstrated that LCA ameliorated DON-caused toxic apoptosis in IPI-2I cells by maintaining cholesterol metabolism. We suggest that as an endogenous metabolite, LCA may be used as a therapeutic and/or integrated into a dietary intervention against mycotoxin toxicity.