# Capsaicin Improves Lipid Metabolism Disorders Caused by LPS-Induced Immune Stress in Weaned Piglets

## TL;DR

Capsaicin helps improve lipid metabolism and reduce inflammation in young pigs under immune stress, potentially benefiting their health and growth.

## Contribution

This study demonstrates that capsaicin modulates lipid metabolism and inflammation in weaned piglets via PPARα and TRPV1 pathways, offering a novel dietary intervention.

## Key findings

- Dietary capsaicin reduces serum and liver lipid accumulation in LPS-induced piglets.
- Capsaicin activates PPARα and TRPV1 pathways to enhance fatty acid oxidation and bile acid metabolism.
- It disrupts the lipid metabolism–inflammation cycle by reducing pro-inflammatory lipid mediators.

## Abstract

Because the immune system and metabolic function of weaned piglets are not yet mature, they are vulnerable to immune stress caused by environmental and pathogenic stimulation, which often leads to lipid metabolism disorders, increased inflammation, and growth retardation. In this study, the immune stress model of weaned piglets was established by LPS induction, and the regulatory effect of capsaicin on lipid metabolism and its molecular mechanism was studied. The results showed that dietary supplementation of 800 mg/kg capsaicin significantly alleviated LPS-induced abnormal elevation of serum and liver triglycerides, non-esterified fatty acids, and low-density lipoprotein cholesterol, and improved bile acid metabolism. In terms of mechanism, capsaicin up-regulates the expression of genes and proteins in the PPARα pathway, consistent with enhanced fatty acid oxidation, down-regulates key genes of fatty acid synthesis, such as FASN and DGAT1, and cholesterol absorption-related genes such as NPC1L, and up-regulates LXRα-ABCG5 and FXR-CYP7A1-MRP4 pathways to enhance cholesterol efflux and bile acid synthesis. In addition, capsaicin also reduces the accumulation of pro-inflammatory lipid mediators such as leukotriene D4 and arachidonic acid, breaking the vicious cycle of ‘lipid metabolism–inflammation’, thereby effectively improving lipid homeostasis and overall health of weaned piglets under immune stress.

The purpose of this study was to investigate the effect of capsaicin (CAP) on lipid metabolism in weaned piglets and its related mechanisms. Twenty-four weaned piglets with an initial body weight of 9.00 ± 0.30 kg were randomly divided into three groups, with eight replicates in each group. The control (CON) and lipopolysaccharide (LPS) groups were fed a basal diet, while the LPS and capsaicin group (LCA) received the basal diet supplemented with 4 mg/kg pure capsaicin (delivered via 800 mg/kg additive) for 35 days. About 4 h before sampling, piglets in the LPS and LCA groups were intraperitoneally injected with LPS at a dose of 100 μg/kg body weight, while those in the CON group were intraperitoneally injected with the same dose of normal saline. In this study, we found that the addition of 800 mg/kg CAP to the diet of piglets significantly reduced the accumulation of serum triglyceride (TG), non-esterified fatty acids (NEFA), and liver fat, and that CAP up-regulates expression of genes and proteins in the PPARα pathway, consistent with enhanced fatty acid oxidation. The intervention with 4 mg/kg CAP was also found to down-regulate cholesterol synthesis precursors (such as mevalonate, MVA), reduce pro-inflammatory phospholipids (such as phosphatidic acid–phosphatidylcholine, PA–PC), and modulate bile acid metabolism, thereby beneficially regulating blood lipid profiles (TC, TG, LDL-C) and disrupting the “lipid metabolism–inflammation” interaction cycle. Furthermore, CAP promoted fatty acid β-oxidation and bile acid metabolism by activating the TRPV1 channel, which alleviated hepatic lipid accumulation. These findings indicated that CAP has potential application value in improving lipid metabolism, intestinal health, and immune function in weaned piglets. However, its long-term safety and dose-dependent effects require further investigation.