Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats

Abstract

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.

Chronomedicine and type 2 diabetes: shining some light on melatonin

“…Tresguerres' group also reported that melatonin reduced age-associated increases in HOMA-IR [131]. Similar studies suggest that melatonin reduces mitochondrial dysfunction [132], inhibits oxidative enzyme activity [133], decreases apoptosis [134], improves dyslipidaemia [135] and reduces diabetes-induced oxidative stress [135]. Together, these rodent studies strengthen the assertion that reductions in melatonin promote insulin resistance and hyperglycaemia, and that these conditions can be corrected with exogenous melatonin administration.…”

Melatonin reduces obesity and restores adipokine patterns and metabolism in obese ( ob/ob ) mice

“…Melatonin supplementation is drawing increased interest in the medical and nutritional research fields [37][38][39]; actually, much of the research focus is on metabolic syndrome obtained mainly in animal models and suggests that melatonin might increase In the photomicrographs, the "*" shows small adipocyte, the " §" shows big adipocytes. The graphs summarize the histomorphometrical analyses, at the visceral and subcutaneous fat levels, respectively, of TNF-α (O), resistin (P), and visfatin (Q).…”

Melatonin Alleviates Liver Apoptosis in Bile Duct Ligation Young Rats

“…Melatonin has been shown to be effective in protecting liver mitochondrial damages in rodent studies [14,21]. To clarify whether BDL-induced apoptosis alterations acted through intrinsic or extrinsic pathway, FADD, cytochrome c, Smac/Diablo and TRAIL-R2/DR5 were examined.…”

“…Mitochondrial structures are highly susceptible to oxidative injury and mitochondrial damages take an important role in cell death [13]. Melatonin is effective in protecting liver mitochondrial damages in diabetic obese rats [14]. …”