Mesenteric Adipocyte Dysfunction in Crohn's Disease is Associated with Hypoxia

Area of Science:

• Gastroenterology
• Adipose Tissue Biology
• Inflammatory Bowel Disease Research

Background:

• Mesenteric adipose tissue (MAT) abnormalities are recognized in Crohn's disease (CD), but functional changes and mechanisms remain unclear.
• This study aimed to analyze MAT function, morphology, and underlying mechanisms in CD patients.

Purpose of the Study:

• To investigate the functional and morphological characteristics of mesenteric adipose tissue (MAT) in Crohn's disease (CD) patients.
• To elucidate the underlying mechanisms contributing to MAT alterations in CD.

Main Methods:

• Collected MAT specimens from CD patients (n=33) and controls (n=23) undergoing intestinal resection.
• Compared hypertrophic MAT (htMAT) and normal MAT (nMAT) from CD patients with control tissues using morphological and molecular techniques.
• Assessed hypoxia via hypoxia-inducible factor 1α expression.

Main Results:

• CD patients' nMAT was similar to controls; however, htMAT showed decreased lipid stores and key enzymes, but increased glucose uptake and lactate.
• htMAT exhibited disorganized structure with increased collagen, inflammatory cytokines (IL-1β, IL-6, TNF-α, MCP-1), and hypoxia (elevated HIF-1α, reduced vascularization).
• Activated TGF-β/Smad and NF-κB pathways were observed in htMAT, potentially linked to hypoxia.

Conclusions:

• Confirmed disorganized structure and dysfunction of mesenteric adipocytes in CD, associated with hypoxia.
• Hypoxia-induced alterations in MAT may play a role in CD pathogenesis.
• Ameliorating mesenteric adipocyte hypoxia could be a therapeutic strategy for CD.