Low linolenic and linoleic acid consumption are associated with chronic kidney disease in patients with type 2 diabetes

Santos, Ana Luiza Teixeira dos; Duarte, Camila Kümmel; Santos, M.P. dos; Zoldan, Maira; Almeida, J. C.; Gross, Jorge Luiz; Azevedo, Mirela Jobim de; Lichtenstein, Alice H.; Zelmanovitz, Themis

doi:10.1371/journal.pone.0195249

Cited by 39 publications

(29 citation statements)

References 36 publications

(46 reference statements)

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“…Linoleic acid and linolenic acid are essential polyunsaturated fatty acids with anti-inflammatory properties. Proper intake of these polyunsaturated fatty acids plays an active role in improving kidney function in patients with DKD ( Garman et al, 2009 ; Mali et al, 2016 ; Dos Santos et al, 2018 ). However, it is shown that the levels of free fatty acids such as linoleic acid and arachidonic acid in the urine of patients with DKD are significantly increased ( Sasaki et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

Urine Metabolomics Analysis in Patients With Normoalbuminuric Diabetic Kidney Disease

Feng

Yang

et al. 2020

Front. Physiol.

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Objective Diabetic kidney disease (DKD) leads to low high albuminuria and gradually progresses to very high albuminuria with kidney insufficiency. However, about 20–40% of DKD is normoalbuminuric DKD (NADKD), which has impaired kidney function but normal urine albumin. This study is to investigate the urine metabolomic profiles of patients with NADKD and albuminuria DKD (ADKD). Methods In total, 95 patients were divided into a simple diabetes mellitus group (SDM group), an ADKD group, and a NADKD group. All subjects were analyzed for urine metabolites using non-targeted metabolomics based on ultra-performance liquid chromatography – tandem mass spectrometry. Results The urine metabolomic profiles of the SDM group, NADKD group, and ADKD group were significantly different, and 65 different metabolites were identified among the three groups. Metabolic pathway analysis of these differential metabolites found that the top three significantly changed metabolic pathways were linoleic acid metabolism, citrate cycle, and, arginine and proline metabolism. There are 12 metabolites enriched in these three metabolic pathways. In detail, compared with those in the SDM group, the levels of γ-linolenic acid in the ADKD group were increased significantly, while the levels of succinic acid, cis -aconitic acid, citric acid, L -proline, L -erythro-4-hydroxyglutamate, N -methylhydantoin, N -carbamoylputrescine, spermidine, and 5-aminopentanoic acid were reduced significantly; compared with those in the NADKD group, the levels of linoleic acid, γ-linolenic acid, and L -malic acid in the ADKD group were increased significantly ( P < 0.05), while the levels of L -proline, L -erythro-4-hydroxyglutamate, N -carbamoylputrescine, and spermidine were significantly reduced ( P < 0.05). However, there were no significant difference between the SDM group and NADKD group ( P > 0.05). Conclusion The urine metabolomic profiles between the NADKD group and the ADKD group are significantly different. Specifically, these two groups have distinct levels of linoleic acid, γ-linolenic acid, L -malic acid, L -proline, L -erythro-4-hydroxyglutamate, N -carbamoylputrescine, and spermidine.

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Section: Discussionmentioning

confidence: 99%

Urine Metabolomics Analysis in Patients With Normoalbuminuric Diabetic Kidney Disease

Feng

Yang

et al. 2020

Front. Physiol.

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“…In this context, it is of interest to note that the 18:2 and 18:3 acyl chains, which are the sole precursors of other NEFAs [ 32 ], are essential fatty acids that cannot be synthesised by mammals [ 33 ]. Further, dietary studies report that an increased intake of NEFA 18:2 and 18:3 is negatively associated with DKD, which supports their importance in disease development [ 34 , 35 ]. One possible implication of the importance of NEFA 18:1, 18:2, and 18:3 and DG 18:2/18:2 is that they promote activation of protein kinase C (PKC) [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 90%

Metabolite aberrations in early diabetes detected in rat kidney using mass spectrometry imaging

et al. 2019

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Diabetic kidney disease is a serious complication of diabetes that can ultimately lead to end-stage renal disease. The pathogenesis of diabetic kidney disease is complex, and fundamental research is still required to provide a better understanding of the driving forces behind it. We report regional metabolic aberrations from an untargeted mass spectrometry imaging study of kidney tissue using an insulinopenic rat model of diabetes. Diabetes was induced by intravenous injection of streptozotocin, and kidneys were harvested 2 weeks thereafter. Imaging was performed using nanospray desorption electrospray ionization connected to a high-mass-resolving mass spectrometer. No histopathological changes were observed in the kidney sections; however, mass spectrometry imaging revealed a significant increase in several 18-carbon unsaturated non-esterified fatty acid species and monoacylglycerols. Notably, these 18-carbon acyl chains were also constituents of several increased diacylglycerol species. In addition, a number of short- and long-chain acylcarnitines were found to be accumulated while several amino acids were depleted. This study presents unique regional metabolic data indicating a dysregulated energy metabolism in renal mitochondria as an early response to streptozotocin-induced type I diabetes. Graphical abstract Electronic supplementary material The online version of this article (10.1007/s00216-019-01721-5) contains supplementary material, which is available to authorized users.

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“…In fact, increased proteinuria, uncontrolled hypertension, and sustained high glucose levels in diabetes and dyslipidemia are well-known risk factors for CKD progression [ 40 , 41 , 42 , 43 ]. Many studies have reported the importance of dietary fat in CKD and CKD progression and have shown the association between dietary fat content and kidney function assessed by albuminuria or the GFR [ 33 , 34 , 35 ]. A lower intake of PUFAs, linoleic acid (LA, C18:2 n -6) and α-linolenic acid (ALA, 18:3 n -3), is related to CKD (24-h urinary albumin excretion of >30 mg and/or GFR of <60 mL/min/1.73 m 2 ) in patients with type 2 diabetes [ 33 , 34 ].…”

Section: Impact Of Dietary Fas On Ckd Risk Predictionmentioning

confidence: 99%

“…Many studies have reported the importance of dietary fat in CKD and CKD progression and have shown the association between dietary fat content and kidney function assessed by albuminuria or the GFR [ 33 , 34 , 35 ]. A lower intake of PUFAs, linoleic acid (LA, C18:2 n -6) and α-linolenic acid (ALA, 18:3 n -3), is related to CKD (24-h urinary albumin excretion of >30 mg and/or GFR of <60 mL/min/1.73 m 2 ) in patients with type 2 diabetes [ 33 , 34 ]. Significantly higher intake of PUFAs and lower intake of MUFAs were found in patients with diabetes and CKD than in patients without CKD in a cross-sectional study [ 34 ].…”

Section: Impact Of Dietary Fas On Ckd Risk Predictionmentioning

confidence: 99%

“…A lower intake of PUFAs, linoleic acid (LA, C18:2 n -6) and α-linolenic acid (ALA, 18:3 n -3), is related to CKD (24-h urinary albumin excretion of >30 mg and/or GFR of <60 mL/min/1.73 m 2 ) in patients with type 2 diabetes [ 33 , 34 ]. Significantly higher intake of PUFAs and lower intake of MUFAs were found in patients with diabetes and CKD than in patients without CKD in a cross-sectional study [ 34 ]. On the contrary, ALA intake was associated with CKD in the Blue Mountains Eye Study with a total of 2600 participants aged ≥50 years [ 35 ].…”

Section: Impact Of Dietary Fas On Ckd Risk Predictionmentioning

confidence: 99%

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Impact of Blood or Erythrocyte Membrane Fatty Acids for Disease Risk Prediction: Focusing on Cardiovascular Disease and Chronic Kidney Disease

Kim

Lee

2018

Nutrients

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Fatty acids (FAs) are essential nutrients and main constituents of cell membranes that are involved in the signaling pathway and associated with health conditions. We investigated if blood or erythrocyte membrane FAs can predict the risk of cardiovascular disease (CVD), chronic kidney disease (CKD), and related complications. Omega-3 (n-3) FAs are important predictors for metabolic syndrome, diabetes, CVD, and CKD risks, and the n-3 index is also a good biomarker for sudden cardiac death in coronary artery disease. Linoleic acid, which is one of the major n-6 FAs reflecting recent dietary FA intake, may predict CVD risk and mortality in the general population and patients with CKD. Monounsaturated FAs (MUFAs) are also related to diabetes or diabetic nephropathy. Oleic acid, a major MUFA, is an emerging marker that is related to acute coronary syndrome, low glomerular filtration rate, and vascular calcification in patients with CKD, and can be modified by n-3 FA supplementation. Saturated FAs, trans-FAs, and FA desaturation/elongation are associated with CVD risk; however, few studies have been conducted on patients with CKD. In summary, blood or erythrocyte membrane FA measurements are important for CVD and CKD risk prediction and management. Further studies are needed to elucidate the FAs for their risk predictions.

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Low linolenic and linoleic acid consumption are associated with chronic kidney disease in patients with type 2 diabetes

Cited by 39 publications

References 36 publications

Urine Metabolomics Analysis in Patients With Normoalbuminuric Diabetic Kidney Disease

Urine Metabolomics Analysis in Patients With Normoalbuminuric Diabetic Kidney Disease

Metabolite aberrations in early diabetes detected in rat kidney using mass spectrometry imaging

Impact of Blood or Erythrocyte Membrane Fatty Acids for Disease Risk Prediction: Focusing on Cardiovascular Disease and Chronic Kidney Disease

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