Cancer cachexia differentially regulates visceral adipose tissue turnover

Area of Science:

• Metabolic Syndrome Research
• Adipose Tissue Biology
• Cancer Pathophysiology

Background:

• Cancer cachexia (CC) is a metabolic syndrome causing severe weight loss, characterized by early fat tissue metabolic derangement and atrophy.
• The role of cellular turnover in adipose tissue (AT) atrophy during CC remains poorly understood.
• Investigating cellular turnover and fibrosis in specific adipose depots is crucial for understanding CC progression.

Purpose of the Study:

• To evaluate the impact of cancer cachexia on cellular turnover and fibrosis in mesenteric (MEAT) and retroperitoneal (RPAT) adipose tissues.
• To determine if changes in AT turnover and fibrosis contribute to AT atrophy in CC.
• To analyze specific markers of cellular turnover and fibrosis in rat models of CC.

Main Methods:

• Cancer cachexia induced in Wistar rats via Walker tumour cell injection; control groups received saline.
• Analysis of AT turnover using Pref1/Adiponectin gene expression ratio and lipolytic protein expression.
• Assessment of apoptosis via CASPASE3 and CASPASE9 activity, and fibrosis via collagen levels and extracellular matrix gene expression.

Main Results:

• RPAT showed decreased Pref1/Adiponectin ratio and activated CASPASE3/9 on day 14, indicating altered cellular turnover.
• Both RPAT and MEAT exhibited increased collagen levels by day 7, suggesting fibrosis.
• MEAT displayed upregulated Collagen1A1, Collagen3A1, Mmp2, and Mmp9 mRNA, indicating significant extracellular matrix remodeling.

Conclusions:

• Cancer cachexia significantly affects cellular turnover in RPAT, potentially driving its atrophy.
• Fibrosis is an early event in both RPAT and MEAT during cancer cachexia.
• While RPAT shows altered cellular turnover, MEAT demonstrates significant fibrotic remodeling, highlighting depot-specific responses in CC.