The joint effect of congenital hypothyroidism and hypercaloric diet consumption as triggers of type 2 diabetes mellitus

Introduction Congenital hypothyroidism affects metabolic and thyroid programming, having a deleterious effect on bodyweight regulation promoting metabolic diseases. This work aimed to demonstrate the development of type 2 diabetes mellitus (T2D) in animals with congenital hypothyroidism, only by the consumption of a mild hypercaloric diet in the extrauterine stage. Methods Two groups of female Wistar rats (n = 9): euthyroid and hypothyroid were used. Hypothyroidism was induced by a thyroidectomy with parathyroid reimplantation. Male offsprings post-weaning were divided into four groups (n = 10): euthyroid, hypothyroid, euthyroid + hypercaloric diet, and hypothyroid + hypercaloric diet. The hypercaloric diet consisted of ground commercial feed plus 20% lard and was administered until postnatal week 40. Bodyweight and energy intake were monitored weekly. Also, metabolic and hormonal markers related to cardiovascular risk, insulin resistance, and glucose tolerance were analyzed at week 40. Then, animals were sacrificed to perform the morphometric analysis of the pancreas and adipose tissue. Results T2D was developed in animals fed a hypercaloric diet denoted by the presence of central obesity, hyperphagia, hyperglycemia, dyslipidemia, glucose tolerance, insulin resistance and hypertension, as well as changes in the cytoarchitecture of the pancreas and adipose tissue related to T2D. The results show that congenital hypothyroid animals had an increase in metabolic markers and an elevated cardiovascular risk. Conclusions Congenital hypothyroid animals develop T2D, having the highest metabolic disturbances and a worsened clinical prognosis than euthyroid animals.

Modification of a model of non-alcoholic fat liver disease in rats with a сombination of a hypercaloric diet and hypodynamia

Introduction. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world, and non-alcoholic steatohepatitis is the second most common cause of liver transplantation in the adult population. An urgent task is to find and develop an optimal model of NAFLD in laboratory animals, which would reproduce all the features of this disease in the clinic.Aim. Modification of the NAFLD model in laboratory animals (rats), which allows the obtained data to be transmitted to humans as fully as possible.Materials and methods. The study was conducted on 52 outbred white male rats of the same age. As the basis of the model, a hypercaloric high-fat diet was used with the addition of food appeal enhancers (sodium glutamate and liquid shrimp extract) and for the first-time conditions of hypodynamia were used – restriction of the motor activity of animals using specially designed cells, in which an individual 11 × 18 cm cell was allocated for each individual. The duration of the study was 12 months. In the course of the experiment, body weight, physical performance, biochemical parameters of blood serum and urine in dynamics were assessed, and lethality was recorded. After the end of the study, the mass of internal organs, visceral and epididymal fat was analyzed, and a histological examination of the liver was performed.Results and discussion. In the course of the experimental study, the development of NAFLD in rats of the control group of animals was histologically confirmed. A high mortality rate was revealed in the group of animals with pathology. Compared with animals of the intact group, a statistically significant increase in their body weight, liver weight, visceral and epididymal fat, a decrease in physical performance, disturbances in lipid, carbohydrate and protein metabolism were revealed, as well as signs of deterioration of the protein synthesis and excretory functions of the liver.Conclusion. A number of advantages of the NAFLD model with a combination of a hypercaloric diet and hypodynamic conditions were revealed, including the similarity of the conditions for the formation and pathogenesis of the disease in experimental animals and humans, which ensures the adequacy of data translation from preclinical practice to clinical practice.

Evaluation of homeopathic medicine in rats subjected to a hypercaloric diet and stress

Introduction: The factors related to obesity are complex, involving biologic, environmental and neuropsychological mechanisms[1-3]. Among the factors which influence the gain of weight, we can consider the stressful factors. Aims: The aim of this experiment was to evaluate the influence of the commercial homeopathic product compound by Fucus vesiculosus 1cH, Thyroidinum 5cH and Calcarea carbonica 5cH (Besomed®) in the gain of weight in animals submitted to hypercaloric diet and stress. Materials and Methods 40 male freshly weaned Wistar rats, ingesting hypercaloric food, were divided into 4 groups, being two groups submitted to stress by standstill, being one group treated and the other one for control (vehicle) and two more groups without stress being one treated and the other one for control. All were given the drink water ad libidum, in blind, for 2 months. The general activity was evaluated by the Open Field method in 2 steps, one after stress and one after 1 month of treatment. The weekly gain of weight was measured during the whole period of treatment. The data were analyzed by the ANOVA method of two ways followed by the Bonferroni test[4], being p≤0,05. Results: The treatment with Besomed® was effective in reducing only the gain of weight in the animals submitted to stress (p≤0,05); the evaluation of general activity in the Open Field showed increase in the time of freezing of these same animals after receiving the stressful stimulus. Discussion: The medicine is used as auxiliary in obesity treatment, and has the same both endogenous highdiluted molecules as the medicine used by similarity, which is the case of Calcarea carbonica, which, among others is indicated for obesity and hyperlipidemia[5], being observed in this study that the homeopathic complex group gained less weight than the other groups. Stress is capable of disturbing the physiological and psychological homeostasia of an individual, and when the stress is caused by standstill, it may induce behavior of the anxious type. There are also studies relating anxiety and feeding behavior in chronically stressed[6] individuals, showing that consuming a hypercaloric diet induces an anxious behavior[7] in male rats. In this study was not observed any change in the motor activity of animals which passed stress, however the time of freezing of the animals which took Besomed® was the lowest (p≤0,05) after stress, if compared to the control groups, demonstrating the absence of an anxious behavior. Conclusion: The medicine evaluated was effective in reducing weight and in inducing an adaptive behavior only in the stressed animals, reducing the evaluated parameters to the same levels observed in the control group.

Blueberry Counteracts Prediabetes in a Hypercaloric Diet-Induced Rat Model and Rescues Hepatic Mitochondrial Bioenergetics

The paramount importance of a healthy diet in the prevention of type 2 diabetes is now well recognized. Blueberries (BBs) have been described as attractive functional fruits for this purpose. This study aimed to elucidate the cellular and molecular mechanisms pertaining to the protective impact of blueberry juice (BJ) on prediabetes. Using a hypercaloric diet-induced prediabetic rat model, we evaluated the effects of BJ on glucose, insulin, and lipid profiles; gut microbiota composition; intestinal barrier integrity; and metabolic endotoxemia, as well as on hepatic metabolic surrogates, including several related to mitochondria bioenergetics. BJ supplementation for 14 weeks counteracted diet-evoked metabolic deregulation, improving glucose tolerance, insulin sensitivity, and hypertriglyceridemia, along with systemic and hepatic antioxidant properties, without a significant impact on the gut microbiota composition and related mechanisms. In addition, BJ treatment effectively alleviated hepatic steatosis and mitochondrial dysfunction observed in the prediabetic animals, as suggested by the amelioration of bioenergetics parameters and key targets of inflammation, insulin signaling, ketogenesis, and fatty acids oxidation. In conclusion, the beneficial metabolic impact of BJ in prediabetes may be mainly explained by the rescue of hepatic mitochondrial bioenergetics. These findings pave the way to support the use of BJ in prediabetes to prevent diabetes and its complications.

Short high fat diet triggers reversible and region specific effects in DCX+ hippocampal immature neurons of adolescent male mice

Adolescence represents a crucial period for maturation of brain structures involved in cognition. Early in life unhealthy dietary patterns are associated with inferior cognitive outcomes at later ages; conversely, healthy diet is associated with better cognitive results. In this study we analyzed the effects of a short period of hypercaloric diet on newborn hippocampal doublecortin+ (DCX) immature neurons in adolescent mice. Male mice received high fat diet (HFD) or control low fat diet (LFD) from the 5th week of age for 1 or 2 weeks, or 1 week HFD followed by 1 week LFD. After diet supply, mice were either perfused for immunohistochemical (IHC) analysis or their hippocampi were dissected for biochemical assays. Detailed morphometric analysis was performed in DCX+ cells that displayed features of immature neurons. We report that 1 week-HFD was sufficient to dramatically reduce dendritic tree complexity of DCX+ cells. This effect occurred specifically in dorsal and not ventral hippocampus and correlated with reduced BDNF expression levels in dorsal hippocampus. Both structural and biochemical changes were reversed by a return to LFD. Altogether these studies increase our current knowledge on potential consequences of hypercaloric diet on brain and in particular on dorsal hippocampal neuroplasticity.

Effect of Salvia officinalis and S. sclarea on rats with a high-fat hypercaloric diet

Phytotherapy for the correction of excess body weight is widely used. However, a comprehensive study of herbal preparations on the organism of model animals has been carried out only for a few plant species. Supplementing the diet of rats with closely related sage species (Salvia officinalis L. and S. sclarea L.) against the background of high-fat hypercaloric diet triggered multidirectional changes in their metabolism. The addition of crushed dry shoots of S. officinalis to the diet of animals led to a sharp increase in their body weight (up to 130.8% of the initial one in 30 days of the experiment). The body weight of the rats treated with S. sclarea for 30 days increased only up to 103.8% of their initial weight and was lower than in the control group. Addition of S. officinalis caused an increase in daily weight gain up to 253.1% of the control group, and S. sclarea – its decrease to 27.8% of the daily weight gain in the control group. In the S. officinalis group, the relative weight of the brain, spleen, and thymus decreased, while in the S. sclarea group, the relative weight of the thymus decreased and that of the colon increased. Under the influence of S. officinalis, the concentration of urea, total bilirubin, and triglycerides in the blood plasma of male rats decreased and the concentration of total protein and the activity of alkaline phosphatase increased. While consuming S. sclarea shoots, there was an increase of alkaline phosphatase activity in the rats’ blood, but atherogenic index (23.1% of the level of the control group) sharply dropped due to an increase in the concentration of high-density lipoprotein cholesterol (286.9% of the control) and a decrease in the concentration of low-density lipoprotein cholesterol (67.7% of control). In rats feeding on S. sclarea shoots, we observed a decrease in the concentration of triglycerides in the blood (39.9% of the control), a decrease in the activity of gamma-glutamyl transferase (62.8%), and an increase in the Ca/P ratio (132.5% of the control group). No significant changes were observed in CBC and WBC differential of male rats when eating S. officinalis and S. sclarea shoots. According to the results of the open field test, the physical and orientational activity of male rats under the influence of S. officinalis significantly decreased by the end of the experiment. Emotional status of rats, on the contrary, decreased when they ate dry crushed shoots of S. sclarea in the composition of the food. Thus, excess body weight of rats in the conditions of hypercaloric diet led to more pronounced deviations from the norm while consuming dry crushed shoots of S. officinalis. The addition of S. sclarea dry crushed shoots to the animals’ diet normalized the body weight in comparison with the control group, reduced the negative manifestations of obesity at the biochemical and organismal levels. In this regard, the substances that contains S. sclarea should be carefully studied for anti-atherosclerotic activity, and tea supplemented with S. sclarea shoots can be recommended as a corrective supplement in the diet of overweight people.

Unraveling the hepatoprotective effects of blueberries in a hypercaloric diet-induced rat model of prediabetes by metabolomic and transcriptomic approaches

Background We previously described protective effects of blueberry juice (BJ) against hepatic steatosis evolution in a hypercaloric diet-induced rat model of prediabetes; however, the underlying mechanisms, are still scarcely explored. Herein, we aim to elucidate the molecular pathways underpinning BJ hepatoprotection on the dysmetabolism evolution in a rat model of prediabetes. Methods A rat model of evolutive prediabetes [Male Wistar rats, 8 weeks old] was developed by ingestion of a high-sucrose (HSu, 35%) diet for 9 weeks (W9), supplemented with a high-fat diet (HF, 60%) for further 14 weeks (HSuHF, W23), vs control with standard diet. Half of the animals (n = 10/group) daily received BJ (25g/Kg BW, orally) between W9 and W23. Along with metabolic characterization, BJ effects on serum and hepatic metabolic surrogates were elucidated using a 1H NMR based metabolomic approach. Moreover, the liver expression of genes (RT-PCR) involved in insulin signaling, lipid metabolism, inflammatory response and mitochondrial respiration was also explored. Values are means ± S.E.M (ANOVA followed by post-hoc tests). Results HSuHF+BJ rats restored hepatic levels of betaine and tend to recover the depletion of glutathione content found in HSuHF animals’ livers. Moreover, BJ positively affected the hepatic mRNA expression of key enzymes and mediators involved in fatty acid oxidation, insulin signalling, inflammatory response, as well as mitochondrial respiratory chain-related genes, which were all downregulated (P < 0.05) in HSuHF animals’ livers. Conclusions Altogether, these molecular findings contribute to explain the mechanisms by which BJ elicits protection against hepatic steatosis and mitochondrial dysfunction induced by hypercaloric diets in the frame of prediabetes evolution.