title: Triglycerides in the human kidney cortex: relationship with body size.
abstract: Obesity is associated with increased risk for kidney disease and uric acid nephrolithiasis, but the pathophysiological mechanisms underpinning these associations are incompletely understood. Animal experiments have suggested that renal lipid accumulation and lipotoxicity may play a role, but whether lipid accumulation occurs in humans with increasing body mass index (BMI) is unknown. The association between obesity and abnormal triglyceride accumulation in non-adipose tissues (steatosis) has been described in the liver, heart, skeletal muscle and pancreas, but not in the human kidney. We used a quantitative biochemical assay to quantify triglyceride in normal kidney cortex samples from 54 patients undergoing nephrectomy for localized renal cell carcinoma. In subsets of the study population we evaluated the localization of lipid droplets by Oil Red O staining and measured 16 common ceramide species by mass spectrometry. There was a positive correlation between kidney cortex trigyceride content and BMI (Spearman R = 0.27, P = 0.04). Lipid droplets detectable by optical microscopy had a sporadic distribution but were generally more prevalent in individuals with higher BMI, with predominant localization in proximal tubule cells and to a lesser extent in glomeruli. Total ceramide content was inversely correlated with triglycerides. We postulate that obesity is associated with abnormal triglyceride accumulation (steatosis) in the human kidney. In turn, steatosis and lipotoxicity may contribute to the pathogenesis of obesity-associated kidney disease and nephrolithiasis.
authors.affiliation: Department of Internal Medicine and the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Ion Alexandru
authors.initials: IA
authors.lastname: Bobulescu
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Tara R
authors.initials: TR
authors.lastname: Rosenthal
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: John T
authors.initials: JT
authors.lastname: Rogers
authors.affiliation: Department of Clinical Sciences and the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Beverley
authors.initials: B
authors.lastname: Adams-Huet
authors.affiliation: Department of Internal Medicine and the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Khashayar
authors.initials: K
authors.lastname: Sakhaee
authors.affiliation: Departments of Internal Medicine, Physiology, and the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Orson W
authors.initials: OW
authors.lastname: Moe
mesh_terms: D000368:Aged; D000818:Animals; D015992:Body Mass Index; D049628:Body Size; D002518:Ceramides / Q000032:analysis; D006801:Humans; D007672:Kidney Cortex / Q000473:pathology*; D007680:Kidney Neoplasms / Q000150:complications / Q000473:pathology; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D011924:Rats, Zucker; D014280:Triglycerides / Q000032:analysis*
chemical_list: D002518:Ceramides; D014280:Triglycerides