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.
Highlights
Obesity is one of the major diseases in the modern world
According to the World Health Organization (WHO), obesity in Europe affects between 20 % and 30 % of adults, while in Ukraine, obesity are harmed 16 % of men and 26 % of women, whereas among children and adolescents, obesity expanded by 11.1 % [5]
The changes we described in high-calorie diet (HCD) group accord with data of other HCD obesity model within 3 and 6 months, namely: lesions of the endocrine part in which some pancreatic islets were fibrotic and disorganized, in the tissues of the pancreas were signs of inflammation, contained macrophages and lymphocytes [21]
Summary
Obesity is one of the major diseases in the modern world. It is a multifactorial disease associated with several metabolic disorders, including insulin resistance, hyperglycemia, dyslipidemia and high blood pressure, which exacerbate each other [1]. They increase the risk of cardiovascular disease and type 2 diabetes, and their combination is called metabolic syndrome. Factors of metabolic syndrome include dysglycemia, atherogenic dyslipidemia, insulin resistance, hypertension and, obesity [2]. About 3.4 million people die from obesity every year, which is more than from underweight at the same time [3]. According to the World Health Organization (WHO), obesity in Europe affects between 20 % and 30 % of adults, while in Ukraine, obesity are harmed 16 % of men and 26 % of women, whereas among children and adolescents, obesity expanded by 11.1 % [5]
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