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

Author(s):  
O. Kalmukova ◽  
K. Chumak ◽  
O. Voronina ◽  
M. Dzerzhynsky

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.

Author(s):  
O. Kalmykova ◽  
M. Dzerzhynsky

The aim of our study was to determine morpho-functional state (area of nucleus, brown adipocytes and also area and number of lipid droplets in each cells, general optical density of tissue) of brown adipose tissue in rats with high-calorie (high fat) dietinduced obesity after melatonin administration in different time of the day (morning and evening). Melatonin was administered daily by gavage for 7 weeks in dose 30 mg/kg either 1 h after lights-on (ZT01) or 1 h before lights-off (ZT11) rats with high-calorie diet (HCD). Besides morphometric parameters as well were measured related visceral fat weight and related brown adipose tissue mass. Rats with HCD had huge changes in brown adipocytes morphology, which summarized in become resembles of classical white adipocytes: grown lipid droplets and cells area, but goes down lipid droplets number and optical density of brown adipose tissue. In general brown adipose tissue with above mentioned characteristic from HCD rats lose their ability to conduct strongly thermoproduction function. After melatonin used in rats with HCD arise leveling of pathological changes, which associated with consumption of HCD. Namely, in groups HCD ZT01 and HCD ZT11 we obtain decreased cells and lipid droplets area, increased lipid droplets number and optical density of brown adipose tissue, in relation to group HCD. Therese received changes has evidence about functionally active brown adipose tissue state, which can also dissipate of exceed energy (lipids – triacylglycerols) amount into whole organism during heat production for avoid to its storage in white adipose tissue and in outside adipose tissue. In addition, evening administration of melatonin (group HCD ZT11) demonstrate more activated state of brown adipose tissueand also related visceral weight gain less, than morning(group HCD ZT01). In conclusions, melatonin influence on morpho-functional state brown adipose tissue in rats with HCD, moreover evening administration can use for obesity therapy via its strong action on activate brown adipocytes.


Author(s):  
I. Vareniuk ◽  
N. Shevchuk ◽  
N. Roslova ◽  
M. Dzerzhynsky

The aim of this work was to determine structural and functional changes in a small intestine of rats after morning and evening administration of melatonin in obese animals during the spring-autumn photoperiod (12L:12D). The obesity was caused with a high-calorie diet for 6 weeks. After that, morning or evening melatonin administrations were given to normal and obese animals at a dose of 30 mg/kg for 7 weeks. After that, paraffin sections of the small intestine were made, on which a state of the mucosa, enterocytes and goblet cells in crypts was morphometrically and visually examined under a microscope. It has been shown, that obesity causes swelling and an increase of thickness of a mucosa, reduction of crypts, a decrease of activity of enterocytes and goblet cells of the small intestine. Introduction of melatonin to animals without obesity causes an increase in thickness of mucosa and a decrease in area of goblet cells. Additionally, after morning melatonin administration a depth of crypts and a height of enterocytes increases. Morning administration of melatonin to obese animals partially recovers crypts and their goblet cells, but doesn't prevent mucosal edema and worsens a state of enterocytes. The evening administration of melatonin partially normalizes all structural changes, caused by obesity. It was concluded, that melatonin may partially correct morpho-functional changes in the small intestine, caused by obesity in the spring and autumn seasons. The evening administration of melatonin to animals with obesity is more effective, than morning administrations. Also, the evening administration of melatonin causes fewer changes in the small intestine of animals without obesity, compared with morning administration.


Author(s):  
O. Kalmukova ◽  
T. Kushmyruk ◽  
M. Dzerzhynsky

Kidneys, like the cardiovascular system, are one of the main target organs, the most vulnerable to obesity, because the first take on the metabolism correction function at an increasing excess of fat tissue in the body. Kidney affection under obesity is a multifactorial thing that is caused by a number of processes, including inflammation, oxidative stress, lipid metabolism disorders, renin-angiotensin-aldosterone system activation, insulin resistance and other factors. An optimal candidate for reducing the harmful effects of kidneys obesity should be a compound that simultaneously exhibits anti-inflammatory and antioxidant properties, controls the circadian rhythm, and also affects on the adipokines secretion. The molecule that meets these conditions is melatonin.The aim of our study was to determine morpho-functional state (morphology characteristic of kidney glomeruli and tubules; morphometric parameters: area and density of glomeruli) of kidney in rats with high-calorie (high fat) diet-induced obesity after melatonin administration in determined time of the day. Melatonin was administered daily by gavage for 7 weeks in dose 30 mg/kg 1 h before lights-off (ZT11) rats with high-calorie diet (HCD). Rats with HCD had huge changes in kidney morphology, which manifested in presence of numerous mesangial cells outside glomeruli and lipid droplets in tubules epithelial cells, while area and density of glomeruli in cm2 decrease. In general kidney with above mentioned characteristic from HCD rats lose their ability to conduct strongly renal function. After melatonin used in rats with HCD arise leveling of pathological changes, which associated with consumption of HCD. Namely, in rats with development obesity melatonin administrations led to increase area and density in comparison to HCD group, moreover glomeruli density reach control values. This is suggest that melatonin have protecting effect against glomerular degeneration. In conclusions, melatonin influence on kidney morpho-functional state in rats with HCD and turn back pathological its changes, moreover evening administration can use for obesity therapy via its strong action on conservation glomerular morphology.


2021 ◽  
Vol 22 (11) ◽  
pp. 6142
Author(s):  
Michael Ezrokhi ◽  
Yahong Zhang ◽  
Shuqin Luo ◽  
Anthony H. Cincotta

The treatment of type 2 diabetes patients with bromocriptine-QR, a unique, quick release micronized formulation of bromocriptine, improves glycemic control and reduces adverse cardiovascular events. While the improvement of glycemic control is largely the result of improved postprandial hepatic glucose metabolism and insulin action, the mechanisms underlying the drug’s cardioprotective effects are less well defined. Bromocriptine is a sympatholytic dopamine agonist and reduces the elevated sympathetic tone, characteristic of metabolic syndrome and type 2 diabetes, which potentiates elevations of vascular oxidative/nitrosative stress, known to precipitate cardiovascular disease. Therefore, this study investigated the impact of bromocriptine treatment upon biomarkers of vascular oxidative/nitrosative stress (including the pro-oxidative/nitrosative stress enzymes of NADPH oxidase 4, inducible nitric oxide (iNOS), uncoupled endothelial nitric oxide synthase (eNOS), the pro-inflammatory/pro-oxidative marker GTP cyclohydrolase 1 (GTPCH 1), and the pro-vascular health enzyme, soluble guanylate cyclase (sGC) as well as the plasma level of thiobarbituric acid reactive substances (TBARS), a circulating marker of systemic oxidative stress), in hypertensive SHR rats held on a high fat diet to induce metabolic syndrome. Inasmuch as the central nervous system (CNS) dopaminergic activities both regulate and are regulated by CNS circadian pacemaker circuitry, this study also investigated the time-of-day-dependent effects of bromocriptine treatment (10 mg/kg/day at either 13 or 19 h after the onset of light (at the natural waking time or late during the activity period, respectively) among animals held on 14 h daily photoperiods for 16 days upon such vascular biomarkers of vascular redox state, several metabolic syndrome parameters, and mediobasal hypothalamic (MBH) mRNA expression levels of neuropeptides neuropeptide Y (NPY) and agouti-related protein (AgRP) which regulate the peripheral fuel metabolism and of mRNA expression of other MBH glial and neuronal cell genes that support such metabolism regulating neurons in this model system. Such bromocriptine treatment at ZT 13 improved (reduced) biomarkers of vascular oxidative/nitrosative stress including plasma TBARS level, aortic NADPH oxidase 4, iNOS and GTPCH 1 levels, and improved other markers of coupled eNOS function, including increased sGC protein level, relative to controls. However, bromocriptine treatment at ZT 19 produced no improvement in either coupled eNOS function or sGC protein level. Moreover, such ZT 13 bromocriptine treatment reduced several metabolic syndrome parameters including fasting insulin and leptin levels, as well as elevated systolic and diastolic blood pressure, insulin resistance, body fat store levels and liver fat content, however, such effects of ZT 19 bromocriptine treatment were largely absent versus control. Finally, ZT 13 bromocriptine treatment reduced MBH NPY and AgRP mRNA levels and mRNA levels of several MBH glial cell/neuronal genes that code for neuronal support/plasticity proteins (suggesting a shift in neuronal structure/function to a new metabolic control state) while ZT 19 treatment reduced only AgRP, not NPY, and was with very little effect on such MBH glial cell genes expression. These findings indicate that circadian-timed bromocriptine administration at the natural circadian peak of CNS dopaminergic activity (that is diminished in insulin resistant states), but not outside this daily time window when such CNS dopaminergic activity is naturally low, produces widespread improvements in biomarkers of vascular oxidative stress that are associated with the amelioration of metabolic syndrome and reductions in MBH neuropeptides and gene expressions known to facilitate metabolic syndrome. These results of such circadian-timed bromocriptine treatment upon vascular pathology provide potential mechanisms for the observed marked reductions in adverse cardiovascular events with circadian-timed bromocriptine-QR therapy (similarly timed to the onset of daily waking as in this study) of type 2 diabetes subjects and warrant further investigations into related mechanisms and the potential application of such intervention to prediabetes and metabolic syndrome patients as well.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Steffen Moritz ◽  
Anja S. Göritz ◽  
Stella Schmotz ◽  
Roland Weierstall-Pust ◽  
Josefine Gehlenborg ◽  
...  

AbstractOverweight and obesity are epidemic conditions. Obesity is associated with somatic and psychological sequelae, including serious life-shortening disorders (e.g., diabetes). This study aimed to evaluate the efficacy of a newly developed imaginal variant of approach bias modification (i.e., imaginal retraining) for the reduction of craving for high-calorie food. In a randomized controlled trial, 384 women with a body mass index above 25 were allocated to a wait-list control group or to two variants of imaginal retraining (ratio: 1; 0.5; 0.5). The two intervention groups were sent a manual on imaginal retraining. One group was explicitly encouraged and instructed to use electronic reminders (RER); the standard retraining group (RS) was not encouraged to use electronic reminders. Assessments were 6 weeks apart and were carried out online. Craving for high-calorie food represented the primary outcome (based on the Visual Analog Scale, VAS). Secondary outcomes included the Food Cravings Questionnaire (FCQ-T-R). The study was registered as DRKS00017220. Women in the RER group utilized the retraining technique more often than those in the RS condition, and utilization frequency in turn was associated with improvement on craving and eating behavior scales. Both intention-to-treat and per-protocol analyses showed a favorable effect of the RER group, which achieved significance on the primary outcome, as well as on several other outcomes relative to controls at a small to medium effect size. For those participants who measured their weight before and after the assessment using a scale, weight loss in the RER group was significantly greater compared to the control group. Both retraining groups (RER: 39.4%; RS: 31.1%) reduced their subjective amount of eating relative to controls (24.2%). Approximately two-thirds of the sample (68.3%) performed the exercises at least once during the study period. The present results show that, when used regularly, imaginal retraining may reduce craving for high-calorie food in overweight and obese women. Of note, there was also evidence suggestive of weight reduction, although no diet or lifestyle change was recommended in the manual. Because a large subgroup neither read the manual nor performed the exercises, we recommend that future imaginal retraining be conveyed via short video clips.


Author(s):  
Amit Sohani ◽  
Chincholikar Sanjeev

Background: The basic cause of obesity is over nutrition easy and increasing availability of energy-dense, high-calorie foods/snacks and drinks are one of the factors that could significantly affect children’s energy intake.Methods: All adolescent school going boys and girls in the age group between 10 to 19 years were included as per definition of adolescent. 585 students were selected by systematic sample i.e. every third student was included in the study sample. A pretested standardized questionnaire which consisted of questions related to sociodemographic data and nutrition was used to screen the population for determining association between nutrition and obesity.Results: It can be observed that 28.21% students were vegetarian while remaining 71.79% were having mixed diet. It can be observed from the Table 2 that overweight and obesity are not related to frequency of consumption of meal, It can be seen that 30.97% overweight subjects had frequent junk food. There was a significant association between frequency of junk food and prevalence of overweight as well as obesity. 25.73% Students with overweight and obese subjects were frequent sweet eaters.Conclusions: Vegetarian diet or non-vegetarian diet did not have any effect on prevalence of underweight, overweight and obesity in adolescent population. Overweight and obesity are not related to frequency of consumption of meal. There was a significant association between frequency of junk foods, sweets with prevalence of overweight as well as obesity.


2020 ◽  
Vol 105 (3) ◽  
pp. e211-e221 ◽  
Author(s):  
Juliane Richter ◽  
Nina Herzog ◽  
Simon Janka ◽  
Thalke Baumann ◽  
Alina Kistenmacher ◽  
...  

Abstract Background The question of whether there is daytime time variation in diet-induced thermogenesis (DIT) has not been clearly answered. Moreover, it is unclear whether a potential diurnal variation in DIT is preserved during hypocaloric nutrition. Objective We hypothesized that DIT varies depending on the time of day and explored whether this physiological regulation is preserved after low-calorie compared with high-calorie intake. Design Under blinded conditions, 16 normal-weight men twice underwent a 3-day in-laboratory, randomized, crossover study. Volunteers consumed a predetermined low-calorie breakfast (11% of individual daily kilocalorie requirement) and high-calorie dinner (69%) in one condition and vice versa in the other. DIT was measured by indirect calorimetry, parameters of glucose metabolism were determined, and hunger and appetite for sweets were rated on a scale. Results Identical calorie consumption led to a 2.5-times higher DIT increase in the morning than in the evening after high-calorie and low-calorie meals (P < .001). The food-induced increase of blood glucose and insulin concentrations was diminished after breakfast compared with dinner (P < .001). Low-calorie breakfast increased feelings of hunger (P < .001), specifically appetite for sweets (P = .007), in the course of the day. Conclusions DIT is clearly higher in the morning than in the evening, irrespective of the consumed calorie amount; that is, this physiological rhythmicity is preserved during hypocaloric nutrition. Extensive breakfasting should therefore be preferred over large dinner meals to prevent obesity and high blood glucose peaks even under conditions of a hypocaloric diet.


2016 ◽  
Vol 116 (11) ◽  
pp. 1954-1965 ◽  
Author(s):  
Emil Kupek ◽  
Adriana S. Lobo ◽  
Danielle B. Leal ◽  
France Bellisle ◽  
Maria Alice A. de Assis

AbstractSeveral studies reported that the timing of eating events has critical implications in the prevention of obesity, but dietary patterns regarding the time-of-day have not been explored in children. The aim of this study was to derive latent food patterns of daily eating events and to examine their associations with overweight/obesity among schoolchildren. A population-based cross-sectional study was conducted with 7–10-year-old Brazilian schoolchildren (n 1232) who completed the Previous Day Food Questionnaire, illustrated with twenty-one foods/beverages in six daily eating events. Latent class analysis was used to derive dietary patterns whose association with child weight status was evaluated by multivariate multinomial regression. Four mutually exclusive latent classes of dietary patterns were identified and labelled according to the time-of-day of eating events and food intake probability (FIP): (A) higher FIP only at lunch; (B) lower FIP at all eating events; (C) higher FIP at lunch, afternoon and evening snacks; (D) lower FIP at breakfast and at evening snack, higher FIP at other meals/snacks. The percentages of children within these classes were 32·3, 48·6, 15·1 and 4·0 %, respectively. After controlling for potential confounders, the mean probabilities of obesity for these classes were 6 % (95 % CI 3·0, 9·0), 13 % (95 % CI 9·0, 17·0), 12 % (95 % CI 6·0, 19) and 11 % (95 % CI 5·0, 17·0), in the same order. In conclusion, the children eating traditional lunch with rice and beans as the main meal of the day (class A) had the lowest obesity risk, thus reinforcing the importance of both the food type and the time-of-day of its intake for weight status.


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