Metabolic disorders induced the changes in the expressions of TNFα, E-cadherin and ultrastructural alteration of liver cells in a typical animal model of type 2 diabetes: Psammomys obesus.

By using a unique animal model of type 2 diabetes mellitus, Psammomys obesus induced by a high-calorie diet (HCD) for nine months, we showed for the first time, in the liver, the impact of inflammation on the remodeling of intercellular junction molecules E-cadherins during the progression of steatohepatitis. Under the effect of HCD, the expressions of immunohistochemical markers, Tumor Necrosis Factor alpha (TNFα) and E-cadherins were inversely correlated. Ultrastructural examination revealed the involvement of destabilization and loss of E-cadherins in the process of hepatic pathogenesis. This mechanical maintenance stress was favored by the recruitment of immune cells which contributed to the triggering and progression of fibrosis by the enlargement of the intercellular space and the invasion of collagen fibers. Furthermore to escape cell death, loss of E-cadherins played a major role in mediating fibrosis. Psammomys obesus is a promising model for experimental research, enabling the extrapolation of observed structural and functional alterations in humans, the objective to find new therapeutic targets. The physiological resemblance between Psammomys obesus and humans enhances the precision and relevance of biomedical research efforts.

The effects of 20-hydroxyecdysone on nuclear shape, heterochromatin quantity and gray-level co-occurrence matrix texture analysis of adrenal zona fasciculata cells in an obese gerbil (Gerbillus tarabuli) model for metabolic syndrome: a correlational study.

The aim of this study was to reveal the effects of obesity and phytotherapy with 20-hydroxyecdysone (20E) on the nuclei of adrenal zona fasciculata (ZF) in the gerbil Gerbillus tarabuli by analyzing nuclear shape and gray-level co-occurrence matrix (GLCM) texture characteristics and by quantifying heterochromatin. Twelve gerbils were divided into three groups: control (C), HC and HC-20E (animals receiving a high-calorie-diet without or with a supplement of 20E, respectively). The adrenals were removed and fixed for histological and statistical analysis. Principal component analysis showed a positive correlation of area, perimeter and textural correlation in C. Nevertheless, a negative correlation was recorded for contrast and entropy. The obesity caused a disorder in nuclear texture; negative correlation was noted with heterochromatin fraction, which may be related to increased ZF activity. However, administration of 20E seems to improve the nuclear state by preserving circularity, uniformity and homogeneity of nuclei as well as the proportion of heterochromatin, which could be a sign of a downregulation of cell activity.Our results suggest that new techniques of image processing could contribute to the understanding of nuclear changes associated with obesity and its possible therapy in this gerbil model for metabolic syndrome.

High-fat/high-carbohydrate-diet short- and middle-term effects on gerbil adrenal zona fasciculata histology.

The adrenals synthesize many hormones involved in the regulation and maintenance of homeostasis. To understand the pathophysiological changes during the development of obesity, a histological study of the adrenal was performed in gerbils receiving a high-fat/high-carbohydrate-diet (HFC) for 8 or 12 weeks. Compared to the controls, the HFC diet increased body weight. Our results reveal significant weight and structural changes in the HFC group's adrenal glands (confirmed by gray level co-occurrence matrix texture and fractal analysis), disorganization of zona fasciculata (8 weeks) and hyperplasia and peri-capillary fibrosis (12 weeks). In conclusion, these results show that an HFC induces time-dependent structural lesions of the adrenals in gerbils, which could be a sign of chronic adaptation of these glands.

High-carbohydrate diet-induced metabolic disorders in Gerbillus tarabuli (a new model of non-alcoholic fatty-liver disease). Protective effects of 20-hydroxyecdysone.

The aim of our study was to reveal the effects of long-term consumption of a high-carbohydrate diet (HCD) on metabolic dysfunctions and histopathological liver alterations in Gerbillus tarabuli, as well as to assess the preventive effects of 20-hydroxyecdysone (20E) in the same animals. Contrary to control diet, HCD induces several metabolic disorders including increased adiposity, dyslipidemia, ectopic fat deposition in the liver, associated with higher levels of plasma AST and ALT. These gerbils showed enhanced oxidative stress with liver damages characteristic of steatohepatitis development. By contrast, adding 20E to HCD resulted in a dose-dependent reduction of all changes induced by HCD. In addition, the hepatoprotective effect of 20E was demonstrated by decreased plasma concentrations of AST, ALT and of hepatic malondialdehyde. Our results suggest that G. tarabuli represents a good model to study diet-induced metabolic disorders and hepatic dysfunctions. Moreover, they demonstrate the efficacy of 20E treatment to counteract the damaging effects of HCD.

Adrenal cortex disorders in a new model of obesity, Gerbillus gerbillus, exposed to a high carbohydrate diet.

Obesity is associated with several endocrine disorders, including hypersensitivity of the hypothalamic-pituitary-adrenal axis. The aim of this study was to investigate the effects of a high carbohydrate diet on structural and ultrastructural features of steroidogenic tissue, as well to evaluate adrenocorticotropic hormone (ACTH), cortisol, and insulin levels in the blood and steroidogenic acute regulatory protein (StAR) expression in the adrenals of gerbils. In electron microscopy, the most pronounced effect of the hypercaloric diet was observed in the zona fasciculata. Plasma levels of ACTH, cortisol, and insulin also showed significant increases. However, no significant change was noted in StAR protein levels. There is evidence that high carbohydrate intake brings about remarkable morphological and functional modifications. This could ultimately lead to mitochondrial alteration and accumulation of lipid droplets, which may lead to inflammation and degeneration of adrenal cells.

Experimental diabetes induced by streptozotocin in the desert gerbil, Gerbillus gerbillus, and the effects of short-term 20-hydroxyecdysone administration.

The present work was aimed at studying the effects of streptozotocin (STZ; 130 mg/kg) in the desert gerbil, Gerbillus gerbillus, and at evaluating the impact of the short-term administration of 20-hydroxyecdysone (20E; 5 mg/kg). We observed that administration of streptozotocin caused a significant increase in plasmatic glucose and a decrease in insulin levels. The plasma lipid profile and liver glycogen content were also altered. The activities of antioxidant enzymes and malondialdehyde (MDA) levels were increased in the pancreatic tissue of STZ-treated gerbils. Moreover, histopathological and immunohistochemical analysis showed degenerative damage in the pancreas with a decline in the percentage area of ß-cells. Treatment of STZ-treated gerbils with 20E counteracted metabolic disorders and reduced lipid peroxidation. Histological and immunohistochemical studies showed moderate amelioration in the pancreatic structure. These findings indicate that streptozotocin administration induced experimental diabetes in gerbils and that short-term administration of 20E has beneficial effects in glucose homeostasis in STZ-treated gerbils suggesting that 20E may stimulate surviving ß-cells to release more insulin.

High carbohydrate diet induces nonalcoholic steato-hepatitis (NASH) in a desert gerbil.

A high intake of sugars has been linked to diet-induced health problems. The aim of this study was to assess whether the long-term consumption of a high-carbohydrate diet (HCD) would cause the hepatic histopathological and metabolic abnormalities that characterize nonalcoholic steatohepatitis (NASH) in a desert gerbil, Gerbillus gerbillus. Compared to natural diet, HCD leads to several metabolic disorders including adiposity, dyslipidemia, insulin resistance, ectopic fat deposition in the liver, which were associated with higher levels of transcripts of genes involved with fat synthesis, endoplasmic reticulum (ER) stress, and fibrosis. In the same way, the experimented animals showed enhanced oxidative stress. Taken together, these results demonstrate that HCD consumption in gerbils induces metabolic disorders and damaged liver, which are key contributors to NASH development. These results suggest that this rodent represents a valuable natural model for human diet-induced metabolic disorders and nonalcoholic fatty liver disease (NAFLD).

Obesity, insulin resistance and diabetes in the sand rat exposed to a hypercaloric diet; possible protective effect for IL1-ß.

It is well established that, upon changing their natural desert low caloric (succulent halophilic plants) to a regular laboratory high caloric diet, sand rats undergo various phenotypic changes depending on their genetic background and including obesity and various degrees of insulin resistance. Our aim was to investigate the acute effects of Interleukin-1ß (IL-1ß) and Interferon-γ (IFN-γ) on glucose-induced insulin secretion in normal lean sand rats maintained on their natural diet and in obese insulin resistant normoglycemic or type 2 diabetic animals after a 9-month high caloric diet. Animals were fed either a low or a high caloric diet; after 9 months, pancreatic islets were isolated and incubated in the presence of increasing cytokine concentrations. At the end of the high-energy diet, animals were all over-weight, and probably due to a different genetic background, they displayed either insulin resistance, hyperinsulinemia and normoglycemia or a marked type-2 diabetic state. Pancreatic islets from obese insulin resistant normoglycemic animals were much more sensitive and responsive to IL-1ß when compared to lean controls. The cytokine was inefficient in diabetic islets. In conclusion, the markedly increased insulinotropic effect of IL-1ß in obese diabetes-resistant sand rat could participate and be involved in pancreatic ß-cell hyperactivity that compensates for insulin resistance and thereby prevent the development of type 2 diabetes in these animals.