Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats.

Area of Science:

• Biochemistry
• Metabolism
• Endocrinology

Background:

• Hepatic mitochondrial dysfunction contributes to liver steatosis and insulin resistance in obesity and type 2 diabetes mellitus (T2DM).
• Antioxidant properties of melatonin may counteract these detrimental effects.

Purpose of the Study:

• To investigate the potential of melatonin in ameliorating hepatic mitochondrial dysfunction and liver steatosis in a rat model of diabesity.

Main Methods:

• Male Zucker diabetic fatty (ZDF) rats and lean littermates (ZL) received oral melatonin (10 mg/kg/day) or vehicle for 6 weeks.
• Evaluated hepatic function via serum enzymes (ALT, AST), liver histopathology, electron microscopy, and mitochondrial function assays.

Main Results:

• Melatonin treatment significantly reduced serum ALT levels, liver steatosis, and vacuolation in ZDF rats.
• Improved mitochondrial function, including increased citrate synthase and complex IV activity, enhanced state 3 respiration, RCR, and ADP/O ratio.
• Augmented ATP production and diminished uncoupling protein 2 levels were observed.

Conclusions:

• Chronic oral melatonin administration effectively reduces liver steatosis and mitochondrial dysfunction in ZDF rats.
• Melatonin demonstrates potential as a therapeutic agent for managing diabesity.