Targeted Lipidomic and Transcriptomic Analysis Identifies Dysregulated Renal Ceramide Metabolism in a Mouse Model of Diabetic Kidney Disease
نویسندگان
چکیده
Both type 1 and type 2 diabetes are associated with altered lipid metabolism, which might in part contribute to debilitating complications such as diabetic kidney disease (DKD). Ceramides are bioactive sphingolipids that have been implicated in a variety of diseases as they can regulate cellular responses to stress and invoke a myriad of downstream signaling responses. To investigate a potential role of altered ceramide metabolism in DKD, we utilized a highly sensitive and specific mass spectrometry (MS) method to quantitatively measure species in plasma and kidney cortex from the C57BLKS db/db mouse model of DKD and littermate controls. Long-chain ceramides (C14:0, C16:0, C18:0, C20:0) and a glucosylceramide (Glu-Cer C18:0) were increased in diabetic mouse plasma, while long-chain (C14:0, C16:0, C18:0) and very-long-chain (C24:0, C24:1) ceramides and a glucosylceramide (Glu-Cer C16:0) were decreased in diabetic mouse kidney tissue. Kidney and plasma ceramide levels correlated to functional and histopathological features of DKD. Transcriptomic analysis of mouse kidney tissue revealed expression changes indicative of decreased ceramide synthesis (Degs2, Smpd2) and increased conversion to sphingosine (Acer2) and downstream sphingosine-1-phosphate signaling. Correlation analysis identified a negative relationship between plasma and kidney tissue levels of ceramide C16:0 and ceramide C24:1. Overall, the findings suggest a previously unrecognized role for ceramide metabolism in DKD.
منابع مشابه
Sphingolipid Metabolism Is Dysregulated at Transcriptomic and Metabolic Levels in the Spinal Cord of an Animal Model of Amyotrophic Lateral Sclerosis
Lipid metabolism is drastically dysregulated in amyotrophic lateral sclerosis and impacts prognosis of patients. Animal models recapitulate alterations in the energy metabolism, including hypermetabolism and severe loss of adipose tissue. To gain insight into the molecular mechanisms underlying disease progression in amyotrophic lateral sclerosis, we have performed RNA-sequencing and lipidomic ...
متن کاملOriganum Majoranum Extract Modulates Gene Expression, Hepatic and Renal Changes in a Rat Model of Type 2 Diabetes
The present study was conducted to test the effect of Origanum Majoranum Extract (OME) of leaves on alterations induced in a model of type 2 diabetic rats. Adult male Wistar rats were fed high fat diet for 3 weeks and injected a single dose of streptozotocin (35 mg/kg) intraperitoneally to induce type 2 diabetic rats. Diabetic rats were given aqueous extract of OME in a dose of 20 mg/kg orally ...
متن کاملOriganum Majoranum Extract Modulates Gene Expression, Hepatic and Renal Changes in a Rat Model of Type 2 Diabetes
The present study was conducted to test the effect of Origanum Majoranum Extract (OME) of leaves on alterations induced in a model of type 2 diabetic rats. Adult male Wistar rats were fed high fat diet for 3 weeks and injected a single dose of streptozotocin (35 mg/kg) intraperitoneally to induce type 2 diabetic rats. Diabetic rats were given aqueous extract of OME in a dose of 20 mg/kg orally ...
متن کاملAltered hepatic lipid metabolism in C57BL/6 mice fed alcohol: a targeted lipidomic and gene expression study.
Chronic alcohol consumption is associated with fatty liver disease in mammals. The object of this study was to gain an understanding of dysregulated lipid metabolism in alcohol-fed C57BL/6 mice using a targeted lipidomic approach. Liquid chromatography tandem mass spectrometry was used to analyze several lipid classes, including free fatty acids, fatty acyl-CoAs, fatty acid ethyl esters, sphing...
متن کاملEffect of Cysteine on Transforming Growth Factor β1 as the Main Cause of Renal Disorder in a Rat Model of Diabetic Nephropathy
Background and purpose: Glycation products, oxidative stress, and inflammation contribute to the development of diabetic nephropathy (DN) due to the elevation of transforming growth factor-β1 (TGF-β1). This study aimed at investigating the effect of Cysteine (Cys) on TGF-β in DN rat model. Materials and methods: In this experimental study, 40 male Wistar rats were randomly divided into four g...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
دوره Suppl 14 شماره
صفحات -
تاریخ انتشار 2015