Sialoadenectomy alters liver cell turn-over and function in mice

Area of Science:

• Hepatology
• Endocrinology
• Cell Biology

Background:

• Submandibular salivary glands produce peptides influencing systemic functions.
• Sialoadenectomy (salivary gland removal) impacts liver regeneration after partial hepatectomy.
• The precise mechanisms linking salivary glands to liver homeostasis remain unclear.

Purpose of the Study:

• To investigate the role of submandibular salivary glands in maintaining liver structure and function.
• To determine the cellular and molecular responses of the liver following sialoadenectomy.
• To assess the liver's functional capacity and sensitivity to stress after gland removal.

Main Methods:

• Sialoadenectomy in mice followed by partial hepatectomy.
• Assessment of hepatocyte death using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assay.
• Measurement of DNA synthesis via bromo-deoxyuridine (BrdU) incorporation.
• Evaluation of liver metabolic function and inflammatory markers under various stress conditions, including bacterial lipopolysaccharide (LPS) challenge.

Main Results:

• Sialoadenectomy resulted in a 40% reduction in hepatocyte number 5 weeks post-surgery.
• A transient increase in hepatocyte apoptosis, but not necrosis, was observed.
• DNA synthesis increased post-sialoadenectomy without a corresponding increase in cell division, leading to larger hepatocytes.
• Liver metabolic functions (glycogen, glucose) remained intact during stress, but sensitivity to LPS/d-galactosamine-induced liver injury was enhanced.

Conclusions:

• A submandibular salivary glands-liver axis is crucial for maintaining liver structure in mice.
• Sialoadenectomy triggers an adaptive response involving apoptosis and compensatory DNA synthesis.
• This adaptive response preserves metabolic liver function but compromises its defense against endotoxins.