Lipid mediators in diabetic nephropathy

Srivastava, Swayam Prakash; Shu, Shi; Koya, Daisuke; Kanasaki, Keizo

doi:10.1186/1755-1536-7-12

Cited by 61 publications

(45 citation statements)

References 73 publications

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“…Metabolic syndrome, which may represent a risk factor for AD in some patients [43], can lead to elevated DAG levels via augmented glycolysis [44]. However, hyperglycemia was not a factor in our MCI and AD cohorts, indicating that this is a minor source for increased circulating levels of DAGs.…”

Section: Discussionmentioning

confidence: 86%

Targeted Lipidomics of Fontal Cortex and Plasma Diacylglycerols (DAG) in Mild Cognitive Impairment and Alzheimer’s Disease: Validation of DAG Accumulation Early in the Pathophysiology of Alzheimer’s Disease

Wood

Medicherla

Sheikh

et al. 2015

JAD

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Previous studies have demonstrated augmented levels of diacylglycerols (DAG) in the frontal cortex and plasma of Alzheimer’s disease (AD) patients. We extended these findings from non-targeted liopidomics studies to design a lipidomics platform to interrogate DAGs and monoacylglycerols (MAG) in the frontal cortex and plasma of MCI subjects. Control subjects included both aged normal controls and controls with normal cognition, but AD pathology at autopsy, individuals termed non-demented AD neuropathology (NDAN). DAGs with saturated, unsaturated, and polyunsaturated fatty acid substituents were found to be elevated in MCI frontal cortex and plasma. Tandem mass spectrometry of the DAGs did not reveal any differences in the distributions of the fatty acid substitutions between MCI and control subjects. While triacylglycerols were not altered in MCI subjects there were increases in monoacylglycerol levels both in the frontal cortex and plasma. In toto, increased levels of DAGs and MAGs appear to occur early in AD pathophysiology and require both further validation in a larger patient cohort and elucidation of the lipidomics alteration(s) that lead to the accumulation of DAGs in MCI subjects.

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Section: Discussionmentioning

confidence: 86%

Targeted Lipidomics of Fontal Cortex and Plasma Diacylglycerols (DAG) in Mild Cognitive Impairment and Alzheimer’s Disease: Validation of DAG Accumulation Early in the Pathophysiology of Alzheimer’s Disease

Wood

Medicherla

Sheikh

et al. 2015

JAD

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“…Furthermore, it has been reported that plasma ceramides are elevated in obese patients with type 2 diabetes mellitus [10]. Most ceramide studies have focused on insulin resistance in the liver, muscle, and adipose tissue; only few have associated increased ceramide levels with renal injury, and most reports on diabetic nephropathy have used extrapolated data from plasma ceramide levels [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Ceramide Accumulation in Podocytes by Myriocin Prevents Diabetic Nephropathy

et al. 2020

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Background: Ceramides are associated with metabolic complications including diabetic nephropathy in patients with diabetes. Recent studies have reported that podocytes play a pivotal role in the progression of diabetic nephropathy. Also, mitochondrial dysfunction is known to be an early event in podocyte injury. Thus, we tested the hypothesis that ceramide accumulation in podocytes induces mitochondrial damage through reactive oxygen species (ROS) production in patients with diabetic nephropathy. Methods: We used Otsuka Long Evans Tokushima Fatty (OLETF) rats and high-fat diet (HFD)-fed mice. We fed the animals either a control-or a myriocin-containing diet to evaluate the effects of the ceramide. Also, we assessed the effects of ceramide on intracellular ROS generation and on podocyte autophagy in cultured podocytes. Results: OLETF rats and HFD-fed mice showed albuminuria, histologic features of diabetic nephropathy, and podocyte injury, whereas myriocin treatment effectively treated these abnormalities. Cultured podocytes exposed to agents predicted to be risk factors (high glucose, high free fatty acid, and angiotensin II in combination [GFA]) showed an increase in ceramide accumulation and ROS generation in podocyte mitochondria. Pretreatment with myriocin reversed GFA-induced mitochondrial ROS generation and prevented cell death. Myriocin-pretreated cells were protected from GFA-induced disruption of mitochondrial integrity. Conclusion: We showed that mitochondrial ceramide accumulation may result in podocyte damage through ROS production. Therefore, this signaling pathway could become a pharmacological target to abate the development of diabetic kidney disease.

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“…2-5 For example, lipids are essential in the regulation of blood vessel permeability, 6 blood clotting, 7,8 diabetic nephropathy, 9 and apoptosis. 10 One particularly fascinating aspect of lipid behavior is the effect that hydration has on lipid function.…”

Section: Introductionmentioning

confidence: 99%

Comparative atomic-scale hydration of the ceramide and phosphocholine headgroup in solution and bilayer environments

Gillams

Lorenz

McLain

2016

The Journal of Chemical Physics

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Previous studies have used neutron diffraction to elucidate the hydration of the ceramide and the phosphatidylcholine headgroup in solution. These solution studies provide bond-length resolution information on the system, but are limited to liquid samples. The work presented here investigates how the hydration of ceramide and phosphatidylcholine headgroups in a solution compares with that found in a lipid bilayer. This work shows that the hydration patterns seen in the solution samples provide valuable insight into the preferential location of hydrating water molecules in the bilayer. There are certain subtle differences in the distribution, which result from a combination of the lipid conformation and the lipid-lipid interactions within the bilayer environment. The lipid-lipid interactions in the bilayer will be dependent on the composition of the bilayer, whereas the restricted exploration of conformational space is likely to be applicable in all membrane environments. The generalized description of hydration gathered from the neutron diffraction studies thus provides good initial estimation for the hydration pattern, but this can be further refined for specific systems. Published by AIP Publishing. [http://dx

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Lipid mediators in diabetic nephropathy

Cited by 61 publications

References 73 publications

Targeted Lipidomics of Fontal Cortex and Plasma Diacylglycerols (DAG) in Mild Cognitive Impairment and Alzheimer’s Disease: Validation of DAG Accumulation Early in the Pathophysiology of Alzheimer’s Disease

Targeted Lipidomics of Fontal Cortex and Plasma Diacylglycerols (DAG) in Mild Cognitive Impairment and Alzheimer’s Disease: Validation of DAG Accumulation Early in the Pathophysiology of Alzheimer’s Disease

Inhibition of Ceramide Accumulation in Podocytes by Myriocin Prevents Diabetic Nephropathy

Comparative atomic-scale hydration of the ceramide and phosphocholine headgroup in solution and bilayer environments

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