Obesity-Initiated Metabolic Syndrome and the Kidney

Abstract

Metabolic syndrome, originally described in 1988 as "syndrome X" by Reaven et al. (1), has evolved in our collective thinking from a vague association of common chronic disease states to a formally defined cluster of clinical traits with adverse impact on cardiovascular risk (2). The cause is incompletely understood but represents a complex interaction among genetic, environmental, and metabolic factors, clearly including diet (3,4) and level of physical activity (4,5). These abnormalities are mediated by-and interconnected by-complex pathways that affect energy homeostasis at cellular, organ, and whole-body levels. This review focuses on obesity-initiated metabolic syndrome, first to provide a pathogenetic overview of extrarenal metabolic derangements; second to consider predisposing conditions shaped by genetic or environmental factors, including growth constraints in utero; and finally to consider the impact of metabolic syndrome on the kidney in its prediabetic phase. The pathogenesis of hypertension in the context of metabolic syndrome is considered separately in this series. Similarly, central nervous system pathways that contribute to disordered energy homeostasis is addressed in detail by others. The mechanisms of irreversible renal injury from hypertension and overt diabetes are well documented and are beyond the scope of this review; nonetheless, they loom large in the long-term renal future of the patient with metabolic syndrome. The current worldwide epidemic of obesity-initiated metabolic syndrome, with its potential for renal damage, mandates our commitment to early renal protection in the obese and to vigorous prevention of obesity in both pediatric and adult populations.

Antilipolytic effect of calcimimetics depends on the allelic variant of calcium-sensing receptor gene polymorphism rs1042636 (Arg990Gly)

“…Recently, obesity was described as a possible independent risk factor for CKD. 16 The underlying mechanism could be overstimulated lipolysis, leading to high levels of circulating FFA, which may elevate kidney damage. 6 Decreasing kidney function leads to the elevation of PTH levels, 17 which may be linked to greater extracellular calcium concentrations needed to activate the CASR.…”

Pathological influence of obesity on renal structural changes in chronic kidney disease

“…Histopathological analysis was performed on the index of glomerular lesion (IGL), incidence of FSGS and sclerotic glomeruli (SG) as described previously [13]. IGL took into account both proliferative and sclerotic changes.…”

Eicosanoids and renal damage in cardiometabolic syndrome

“…Interestingly. FFA can generate ROS that also contribute to the renal injury [1,53]. As a whole, elevated ROS and FFA levels are factors that contribute to the endothelial dysfunction and progression of chronic kidney disease in cardiometabolic syndrome.…”

“…Elevated levels of intracellular lipids will result in lipid products like diacylglyceride and ceramide that have been implicated as mediators of cell death or what is known as apoptosis [1,52]. Increased FFA levels have the potential to cause tubulointerstitital nephritis in metabolic syndrome [1,53]. Interestingly.…”

“…Obesity is the central phenotype in metabolic syndrome, also known as cardiometabolic syndrome that clusters with other cardiovascular risk factors. These other cardiovascular risk factors include hypertension, type 2 diabetes, insulin resistance, low high-density lipoproteins (HDL) cholesterol, elevated triglycerides, microalbuminuria, and atherosclerosis [1,2,3] (Figure 1). The Adult treatment Panel II of the National Cholesterol Education Program has defined metabolic syndrome as any three of the following five traits: visceral obesity, hypertension, hypertriglyceridemia, low HDL cholesterol, and impaired fasting glucose [4].…”