Morpho-functional state of rat pancreas under melatonin administration during obesity development: chronotherapeutic approach

Abstract

Overweight and obesity often cause some comorbidity like insulin resistance, diabetes type 2, cancer, cardio-vascular pathology etc. Pancreas is the important organ in carbohydrate metabolism and insulin signaling, that under obesity conditions undergo pathologic changes. For diminish adverse effects of obesity in the role of therapeutic agent is considered melatonin – pineal gland pleiotropic multifunctional molecule. In view of development precision medicine, which include processing personalized data of whole genome sequencing, microbiome, individual day/night regime etc., time selection of drug administration for maximize efficacy and minimize side effects to each patient in according of private organism circadian rhythm is the main goal of chronotherapy approach. The aim of our study was to determine morpho-functional state (morphology characteristic of exocrine and endocrine part; morphometric parameters: areas of pancreatic islets, acini and acinar cell nucleus) of pancreas in rats with high-calorie (high fat) diet-induced obesity after melatonin administration in determined time of the day (evening and morning). Melatonin was administered daily by gavage for 7 weeks in dose 30 mg/kg 1 h before lights-off (ZT11, evening) or 1 h after lights-on (ZT01, morning) rats with high-calorie diet (HCD). Rats with HCD had morbid changes in pancreas cells morphology of exocrine and endocrine part, which manifested in presence of macrophage and leukocyte infiltration of islets, vacuolization and lipid droplets in acinocytes cytoplasm, while areas of islets, acini and acinar cell nucleus decreased. Obese rats with melatonin administration demonstrate amelioration of HCD-associated changes in pancreas. Namely, in rats with development obesity melatonin administrations increased area of pancreatic islets in comparison to HCD group, moreover pancreas acini area reach control values. Also were observed difference between time-of-day interventions of melatonin on acinar cell nucleus area parameters: evening administration showed more strong action in increased to control level direction. Together, is suggesting about melatonin ameliorative role on morpho-functional state of pancreas exocrine and endocrine part under HCD-induced obesity conditions, additionally evening administration 1 h before light-off displayed more beneficial influence compared to morning.