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Updated: Mar 7, 2026
Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
Published on: January 31, 2025
Anti-inflammatory Function of High-Density Lipoproteins via Autophagy of IκB Kinase
Ragam Gerster1, Jyrki J Eloranta2, Martin Hausmann3
1Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland; Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Schlieren, Switzerland; Zurich Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
Insights
High-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I) reduce intestinal inflammation by inducing autophagy, offering potential new treatments for inflammatory bowel disease (IBD).
Area of Science:
- Gastroenterology
- Immunology
- Lipid Metabolism
Background:
- Decreased high-density lipoprotein (HDL) cholesterol is common in inflammatory bowel disease (IBD).
- HDL possesses anti-inflammatory properties.
- The role of HDL and apolipoprotein A-I (apoA-I) in IBD mucosal inflammation requires further investigation.
Purpose of the Study:
- To investigate the effects of HDL and apoA-I on inflammatory responses in the gut.
- To determine the mechanisms by which HDL and apoA-I modulate intestinal inflammation.
- To evaluate the therapeutic potential of HDL and apoA-I in IBD models.
Main Methods:
- In vitro studies using T84 intestinal cells to assess HDL's impact on cytokine expression (TNF, IL-8) and NF-κB activity.
- In vivo studies using mouse models of colitis (DSS and TNBS) in apoA-I knockout, transgenic, and wild-type mice.
- Analysis of mucosal damage, myeloperoxidase (MPO) activity, inflammatory markers, and autophagy pathways.
Main Results:
- HDL and apoA-I suppressed TNF-induced inflammatory gene expression and NF-κB activation in vitro.
- ApoA-I knockout mice exhibited exacerbated colitis symptoms, increased mucosal damage, and higher inflammatory markers compared to wild-type and apoA-I transgenic mice.
- HDL treatment induced autophagy, which inhibited NF-κB activation and subsequent cytokine production.
Conclusions:
- HDL and apoA-I demonstrate significant anti-inflammatory effects in the intestine.
- Autophagy induction by HDL plays a key role in suppressing intestinal inflammation.
- HDL and apoA-I represent promising therapeutic targets for managing inflammatory bowel disease.
Background & Aims:
Plasma levels of high-density lipoprotein (HDL) cholesterol are frequently found decreased in patients with inflammatory bowel disease (IBD). Therefore, and because HDL exerts anti-inflammatory activities, we investigated whether HDL and its major protein component apolipoprotein A-I (apoA-I) modulate mucosal inflammatory responses in vitro and in vivo.
Methods:
The human intestinal epithelial cell line T84 was used as the in vitro model for measuring the effects of HDL on the expression and secretion of tumor necrosis factor (TNF), interleukin-8 (IL-8), and intracellular adhesion molecule (ICAM). Nuclear factor-κB (NF-κB)-responsive promoter activity was studied by dual luciferase reporter assays. Mucosal damage from colitis induced by dextran sodium sulphate (DSS) and 2,4,6-trinitrobenzenesulfonic acid (TNBS) was scored by colonoscopy and histology in apoA-I transgenic (Tg) and apoA-I knockout (KO) and wild-type (WT) mice. Myeloperoxidase (MPO) activity and TNF and ICAM expression were determined in intestinal tissue samples. Autophagy was studied by Western blot analysis, immunofluorescence, and electron microscopy.
Results:
HDL and apoA-I down-regulated TNF-induced mRNA expression of TNF, IL-8, and ICAM, as well as TNF-induced NF-κB-responsive promoter activity. DSS/TNBS-treated apoA-I KO mice displayed increased mucosal damage upon both colonoscopy and histology, increased intestinal MPO activity and mRNA expression of TNF and ICAM as compared with WT and apoA-I Tg mice. In contrast, apoA-I Tg mice showed less severe symptoms monitored by colonoscopy and MPO activity in both the DSS and TNBS colitis models. In addition, HDL induced autophagy, leading to recruitment of phosphorylated IκB kinase to the autophagosome compartment, thereby preventing NF-κB activation and induction of cytokine expression.
Conclusions:
Taken together, the in vitro and in vivo findings suggest that HDL and apoA-I suppress intestinal inflammation via autophagy and are potential therapeutic targets for the treatment of IBD.
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