Childhood-Adolescent Obesity in the Cardiorenal Syndrome: Lessons from Animal Models

Abstract

Background/Aims: Childhood-adolescent overweight and obesity have grown to pandemic proportions during the past decade. The onset of obesity in younger adults will likely be manifested as earlier onset of myocardial and renal end-organ disease in younger adults. For the first time, it is estimated that the current generation may not live to be as old as their parents. Thus, it is important to develop animal models of childhood obesity to understand fundamental pathological organ changes. Methods: In this regard, we utilize transmission electron microscopy evaluation to evaluate early remodeling changes of two adolescent rodent obesity models: the Zucker obese (fa/fa) rat and the db/db mouse models of obesity. We have concentrated on the initial ultrastructural remodeling (obese adipose tissue, skeletal muscle, and islet remodeling) and the associated changes in target end organs (including the myocardium and kidney) in young rodent models of obesity and insulin resistance, collectively manifesting as the cardiorenal metabolic syndrome (CRS). Results: Briefly, tissues revealed the following ultrastructural remodeling abnormalities: inflammation, hypertrophy, and early fibrosis in adipose tissue; loss of mitochondria in skeletal muscles, hyperplasia, fibrosis, and depletion of insulin-secretory granules in pancreatic islets; increased intramyocardial lipid accumulation, fibrosis, and mitochondrial deposition in the myocardium, and obesity-related glomerulopathy and tubulopathy in the kidney. Conclusion: Based on the current knowledge and ultrastructural observations of organ pathology, we propose mechanisms whereby obesity appears to be the driving force behind the development of the CRS.

Dietary sodium restriction prevents kidney damage in high fructose-fed rats

“…It is suggested that the renal reduction in oxidative stress and proinflammatory cytokines is very likely to be related to the prevention of subsequent podocyte injury and fibrosis. A possible link between adipose tissue and renal damages as suggested in childhood-adolescent obesity 52 deserves further investigation in the beneficial influence of dietary sodium restriction in fructose-fed rats.…”

An Immediate and Long-Term Complication of COVID-19 May Be Type 2 Diabetes Mellitus: The Central Role of β-Cell Dysfunction, Apoptosis and Exploration of Possible Mechanisms

“…Islet fibrosis is related to systemic (cRAAS) and islet RAAS (tRAAS) ( Section 2 ), islet redox stress and RONS ( Section 3 ) and systemic and islet inflammation ( Section 4 ). Islet fibrosis is a common finding early on in MetS and T2DM, which is found not only in preclinical animal models ( Figure 8 ) but also in adult humans ( Figure 9 ) [ 20 , 22 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ]. The pancreatic stellate cell is important [ 48 , 50 ] and may reflect the activation of the peri-islet pericytes in the Ren2 model of lean hypertension with excess renin and Ang II ( Figure 8 ).…”

Animal Models to Study Links between Cardiovascular Disease and Renal Failure and Their Relevance to Human Pathology

“…These abnormalities precede the development of albuminuria and glomerular injury and animals show a parallel deterioration in cardiac output and renal function ( 89 ). Ultrastructural studies have shown cardiomyopathy in both the OZ rat, and in mice with a similar mutation (db/db mouse) ( 90 ). A comprehensive analysis in the db/db mouse has shown that albuminuria/glomerulopathy and cardiac contractile dysfunction appear after 2–4 months of hyperglycemia ( 91 ).…”