Renal Lipid Metabolism Abnormalities in Obesity and Clear Cell Renal Cell Carcinoma.

Ion Alexandru Bobulescu,Christian Rivera,Subash Kairamkonda,Sabiha Khatoon,Laurentiu M Pop,Raquibul Hannan,Chinnadurai Mani,Komaraiah Palle,Kala Turner

doi:10.3390/metabo11090608

Abstract

Clear cell renal cell carcinoma is the most common and deadly type of cancer affecting the kidney, and is characterized histologically by large intracellular lipid deposits. These deposits are thought to result from lipid metabolic reprogramming occurring in tumor cells, but the exact mechanisms and implications of these metabolic alterations are incompletely understood. Obesity is an independent risk factor for clear cell renal cell carcinoma, and is also associated with lipid accumulation in noncancerous epithelial cells of the proximal tubule, where clear cell renal cell carcinoma originates. This article explores the potential link between obesity-associated renal lipid metabolic disturbances and lipid metabolic reprogramming in clear cell renal cell carcinoma, and discusses potential implications for future research.

Highlights

Kidney cancer represents approximately 2.2% of all new cancer cases and 1.8% of cancer deaths globally [1]
Renal cell carcinomas (RCCs) are primary adenocarcinomas originating from renal tubular epithelial cells, and are the most common type of kidney cancer (90–95% of all cases)
Clear cell renal cell carcinoma, which is thought to arise from proximal tubule epithelial cells [3], is the most common and deadly subtype (75–80% of all cases of RCC) [4,5,6]

Summary

Introduction

Kidney cancer represents approximately 2.2% of all new cancer cases and 1.8% of cancer deaths globally [1]. The characteristic “clear cell” (or empty cytoplasm) appearance of ccRCC on standard histological examination is due to the intracellular accumulation of large amounts of lipid, and some glycogen, which are washed out during the standard sample preparation procedure [8,9]. These large lipid depots indicate that lipid metabolic reprogramming is a central feature of ccRCC, but the roles played by lipid accumulation in the biology and pathogenesis of ccRCC remain incompletely understood. We review the pathophysiologic mechanisms and implications of lipid accumulation in ccRCC and in non-cancerous proximal tubule cells, and propose a new research direction examining the link between obesity-related renal lipid accumulation and ccRCC pathogenesis

Lipid Uptake and Metabolism in Normal Proximal Tubule Cells

Lipid Metabolic Disturbances in Non-Cancerous Proximal Tubule Cells

Lipid Metabolic Reprogramming in ccRCC

Exploring the Link between Obesity and Renal Cell Carcinoma

Findings

Conclusions