Obesity and Kidney Disease

Differential Effects of Obesity on Adipose Tissue and Kidney Inflammation and Fibrosis

Anne-Emilie Declèves; Kumar Sharma

Disclosures

Curr Opin Nephrol Hypertens. 2015;24(1):28-36. 

In This Article

Abstract and Introduction

Abstract

Purpose of review To provide a perspective by investigating the potential cross-talk between the adipose tissue and the kidney during obesity.

Recent findings It is well established that excessive caloric intake contributes to organ injury. The associated increased adiposity initiates a cascade of cellular events that leads to progressive obesity-associated diseases such as kidney disease. Recent evidence has indicated that adipose tissue produces bioactive substances that contribute to obesity-related kidney disease, altering the renal function and structure. In parallel, proinflammatory processes within the adipose tissue can also lead to pathophysiological changes in the kidney during the obese state.

Summary Despite considerable efforts to better characterize the pathophysiology of obesity-related metabolic disease, there are still a lack of efficient therapeutic strategies. New strategies focused on regulating adipose function with respect to AMP-activated protein kinase activation, NADPH oxidase function, and TGF-β may contribute to reducing adipose inflammation that may also provide renoprotection.

Introduction

The growing epidemic of obesity, particularly in the western world, is a major factor in reducing the expected life-expectancy, and is an added serious health and economic burden. The epidemic of obesity is related to the combination of sedentary lifestyle, usually associated with a high caloric intake and a lack of exercise. A possible scenario is that when the energy intake exceeds the storage capacity of white adipose tissue (WAT), ectopic lipid accumulation in ectopic organs is induced,[1] promoting metabolic disturbances such as insulin resistance and alteration in the control of glucose and lipid metabolisms, contributing to hyperglycemia, dyslipidemia, hypertension, insulin resistance, glucose intolerance, and atherosclerosis.[2] Moreover, central obesity is a major risk factor for diabetes and hypertension, which together account for about 70% of all cases of end-stage renal disease (ESRD).[3] However, a full understanding of the mechanisms involved in progressive renal disease is still absent.

WAT is not only a simple fat storage organ, but also now recognized as a dynamic tissue involved in the production of adipokines such as leptin, adiponectin, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), transforming growth factor-beta (TGF-β), and angiotensin II (ANG II).[4,5] The balance between these adipokines allows the adipose tissue to regulate the appetite, food intake, glucose clearance, and energy expenditure. The perturbation of this balance during obesity promotes a proinflammatory environment and leads to insulin resistance. Obesity-related kidney disease is associated with renal hemodynamic abnormalities, endothelial and podocyte dysfunction, glomerular basement membrane thickening and mesangial expansion, tubular atrophy, interstitial fibrosis, and a progressive decrease in renal function [increased albuminuria and decreased glomerular filtration rate (GFR)], leading to ESRD.[6–9] Assuming that common factors exist between obesity-induced adipose tissue and kidney disease, here we will discuss the potential cross-talk between both tissues during obesity.

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