Hepatic
mitochondrial dysfunction is thought to play a role in the development of
liver steatosis and
insulin resistance, which are both common characteristics of
obesity and
type 2 diabetes mellitus (T2DM). It was hypothesized that the
antioxidant properties of
melatonin could potentially improve the impaired functions of hepatic mitochondria in diabetic obese animals. Male Zucker diabetic fatty (ZDF) rats and lean littermates (ZL) were given either
melatonin (10 mg/kg BW/day) orally for 6 wk (M-ZDF and M-ZL) or vehicle as control groups (C-ZDF and C-ZL). Hepatic function was evaluated by measurement of serum
alanine transaminase and
aspartate transaminase levels, liver histopathology and electron microscopy, and hepatic mitochondrial functions. Several impaired functions of hepatic mitochondria were observed in C-ZDF in comparison with C-ZL rats.
Melatonin treatment to ZDF rats decreases serum levels of ALT (P < 0.001), alleviates
liver steatosis and vacuolation, and also mitigates diabetic-induced mitochondrial abnormalities,
glycogen, and
lipid accumulation.
Melatonin improves
mitochondrial dysfunction in M-ZDF rats by increasing activities of mitochondrial
citrate synthase (P < 0.001) and complex IV of electron transfer chain (P < 0.05) and enhances state 3 respiration (P < 0.001), respiratory control index (RCR) (P < 0.01), and phosphorylation coefficient (
ADP/O ratio) (P < 0.05). Also
melatonin augments
ATP production (P < 0.05) and diminishes
uncoupling protein 2 levels (P < 0.001). These results demonstrate that chronic oral
melatonin reduces
liver steatosis and
mitochondria dysfunction in ZDF rats. Therefore, it may be beneficial in the treatment of diabesity.