Evaluating the Impact of Different Hypercaloric Diets on Weight Gain, Insulin Resistance, Glucose Intolerance, and its Comorbidities in Rats

Abstract

Animal experimentation has a long history in the study of metabolic syndrome-related disorders. However, no consensus exists on the best models to study these syndromes. Knowing that different diets can precipitate different metabolic disease phenotypes, herein we characterized several hypercaloric rat models of obesity and type 2 diabetes, comparing each with a genetic model, with the aim of identifying the most appropriate model of metabolic disease. The effect of hypercaloric diets (high fat (HF), high sucrose (HSu), high fat plus high sucrose (HFHSu) and high fat plus streptozotocin (HF+STZ) during different exposure times (HF 3 weeks, HF 19 weeks, HSu 4 weeks, HSu 16 weeks, HFHSu 25 weeks, HF3 weeks + STZ) were compared with the Zucker fatty rat. Each model was evaluated for weight gain, fat mass, fasting plasma glucose, insulin and C-peptide, insulin sensitivity, glucose tolerance, lipid profile and liver lipid deposition, blood pressure, and autonomic nervous system function. All animal models presented with insulin resistance and dyslipidemia except the HF+STZ and HSu 4 weeks, which argues against the use of these models as metabolic syndrome models. Of the remaining animal models, a higher weight gain was exhibited by the Zucker fatty rat and wild type rats submitted to a HF diet for 19 weeks. We conclude that the latter model presents a phenotype most consistent with that observed in humans with metabolic disease, exhibiting the majority of the phenotypic features and comorbidities associated with type 2 diabetes in humans.

A2 Adenosine Receptors Mediate Whole-Body Insulin Sensitivity in a Prediabetes Animal Model: Primary Effects on Skeletal Muscle

“…Surprisingly, chronic A 2A blockade, increased total fat in female, while decreased total fat mass in male, which contrasts with the lack of effects of the deletion of A 2A receptors in mice in body weight (46). As previously described, 4 weeks of HSu diet were unable to promote significant changes in weight gain (8,47), being this effect also observed with the blockade of the adenosine receptors. However, even without any change in weight gain, chronic blockade of A 1 receptors in HSu female animals decreased total fat mass, which was associated with a decrease in perienteric, genital, and perinephric fat mass, suggesting a redistribution of fat depots or an altered ratio lean/fat mass.…”

“…Also, in an obese mice model with insulin resistance induced by 16 weeks of high-fat diet, the expression of A 2B adenosine receptor is increased in the liver, visceral fat, and gastrocnemius muscle (54). Based on this, we can postulate that the differences in the expression of adenosine receptors might be related with differences in the animal models studied, the HSu model studied in the present work is a lean model of insulin resistance (8,47), or with the degree of insulin resistance and disease progression, as herein we used a 4 weeks model of diet and Johnston-Cox et al (54) submitted the animals to 16 weeks of high-fat diet. Therefore, different metabolic disturbances and different stages of disease progression might contribute differently to the expression of adenosine receptor in the insulin sensitive tissues.…”

GQ‐130, a novel analogue of thiazolidinedione, improves obesity‐induced metabolic alterations in rats: Evidence for the involvement of PPARβ/δ pathway

“…The mechanism by which obesity increased blood pressure is not completely understood, but among other factors, endothelial dysfunction and insulin resistance seem to be involved in the development of hypertension in MS. Many authors believe that insulin resistance itself or the resulting hyperinsulinaemia (a compensatory response to insulin resistance) is responsible for increased retention of sodium and water reabsorption by the kidneys, accelerating the renal damage and activating the sympathetic nervous system . Several studies have investigated the impact of high‐fat or high‐carbohydrate diets on blood pressure and baroreflex .…”

The Metabolic Syndrome: Emerging Novel Insights Regarding the Relationship between the Homeostasis Model Assessment of Insulin Resistance and other Key Predictive Markers in Young Adults of Western Algeria

“…In 2016, more than 1.9 billion adults were overweight and, from these, more than 650 million were obese. If recent trends continue unabated, up to 20% of the world's adult population (1.2 billion individuals) is expected to be obese by 2030 [7,8]. Persistent obesity dysregulates metabolic processes, including action of insulin on glucose-lipid-free fatty acid metabolism, and severely affects processes controlling blood glucose, blood pressure and lipids.…”