Obese mothers supplemented with melatonin during gestation and lactation ameliorate the male offspring’s pancreatic islet cellular composition and beta-cell function

Abstract

Melatonin supplementation to obese mothers during gestation and lactation might benefit the pancreatic islet cellular composition and beta-cell function in male offspring adulthood. C57BL/6 females (mothers) were assigned to two groups (n = 20/each) based on their consumption in control (C 17% kJ as fat) or high-fat diet (HF 49% kJ as fat). Mothers were supplemented with melatonin (Mel) (10 mg/kg daily) during gestation and lactation, or vehicle, forming the groups (n = 10/each): C, CMel, HF, and HFMel. The male offspring were studied, considering they only received the C diet after weaning until three months old. The HF mothers and their offspring showed higher body weight, glucose intolerance, insulin resistance, and low insulin sensitivity than the C ones. However, HFMel mothers and their offspring showed improved glucose metabolism and weight loss than the HF ones. Also, the offspring’s higher expressions of pro-inflammatory markers and endoplasmic reticulum (ER) stress were observed in HF but reduced in HFMel. Contrarily, antioxidant enzymes were less expressed in HF but improved in HFMel. In addition, HF showed increased beta-cell mass and hyperinsulinemia but diminished in HFMel. Besides, the beta-cell maturity and identity gene expressions diminished in HF but enhanced in HFMel. In conclusion, obese mothers supplemented with melatonin benefit their offspring’s islet cell remodeling and function. In addition, improving pro-inflammatory markers, oxidative stress, and ER stress resulted in better glucose and insulin levels control. Consequently, pancreatic islets and functioning beta cells were preserved in the offspring of obese mothers supplemented with melatonin.

Circadian desynchrony and glucose metabolism

“…Melatonin supplementation reduces insulin resistance in rodent models, including diabetes mellitus models. [186][187][188][189] Moreover, in these rodent models melatonin reduces plasma insulin levels, 190 and reduces fasting blood glucose levels by stimulating hepatic glycogen synthesis 191,192 and by suppressing hepatic gluconeogenesis. 193 On the other hand, pinealectomy in rodents impairs diurnal glucose rhythms and insulin secretion.…”

“…In nocturnal rodents, evidence mostly demonstrates a positive influence of melatonin supplementation on glucose homeostasis. Melatonin supplementation reduces insulin resistance in rodent models, including diabetes mellitus models 186‐189 . Moreover, in these rodent models melatonin reduces plasma insulin levels, 190 and reduces fasting blood glucose levels by stimulating hepatic glycogen synthesis 191,192 and by suppressing hepatic gluconeogenesis 193 .…”