scholarly journals Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy

2013 ◽  
Vol 55 (3) ◽  
pp. 561-572 ◽  
Author(s):  
Michal Herman-Edelstein ◽  
Pnina Scherzer ◽  
Ana Tobar ◽  
Moshe Levi ◽  
Uzi Gafter
Keyword(s):  
Diabetic Nephropathy ◽  
Lipid Metabolism ◽  
Lipid Accumulation

scholarly journals The Attenuation of Diabetic Nephropathy by Annexin A1 via Regulation of Lipid Metabolism through AMPK/PPARα/CPT1b Pathway

2021 ◽  
Author(s):  
Liang Wu ◽  
Changjie Liu ◽  
Dong-Yuan Chang ◽  
Rui Zhan ◽  
Mingming Zhao ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
Annexin A1 ◽  
Diabetic Mice ◽  
Tubulointerstitial Lesions ◽  
Matrix Expansion ◽  
Elevated Expression ◽  
Abnormal Metabolism ◽  
Proximal Tubular Epithelial Cells

Inflammation and abnormal metabolism play important roles in the pathogenesis of diabetic nephropathy (DN). Annexin A1 (ANXA1) contributes to inflammation resolution and improves metabolism. Here, we assess the effects of ANXA1 in diabetic mice and proximal tubular epithelial cells (PTECs) treated with high glucose plus palmitate acid (HGPA), and explore the association of ANXA1 with lipid accumulation in DN patients. It is found that ANXA1 deletion aggravates renal injuries, including albuminuria, mesangial matrix expansion and tubulointerstitial lesions in HFD/STZ-induced diabetic mice. ANXA1 deficiency promotes intra-renal lipid accumulation and drives mitochondrial alterations in kidneys. In addition, Ac2-26, an ANXA1 mimetic peptide, has a therapeutic effect against lipid toxicity in diabetic mice. In HGPA-treated human PTECs, <i>ANXA1</i> silencing causes FPR2/ALX-driven deleterious effects, which suppress phosphorylated Thr<sup>172</sup>AMPK, resulting in decreased PPARα and CPT1b expression and increased HGPA-induced lipid accumulation, apoptosis and elevated expression of pro-inflammatory and pro-fibrotic genes. Last but not least, the extent of lipid accumulation correlates with renal function, and the level of tubulointerstitial ANXA1 expression correlates with ectopic lipid deposition in kidneys of DN patients. These data demonstrate that ANXA1 regulates lipid metabolism of PTECs to ameliorate disease progression, hence it holds great potential as a therapeutic target for DN.

scholarly journals The Attenuation of Diabetic Nephropathy by Annexin A1 via Regulation of Lipid Metabolism through AMPK/PPARα/CPT1b Pathway

2021 ◽  
Author(s):  
Liang Wu ◽  
Changjie Liu ◽  
Dong-Yuan Chang ◽  
Rui Zhan ◽  
Mingming Zhao ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
Annexin A1 ◽  
Diabetic Mice ◽  
Tubulointerstitial Lesions ◽  
Matrix Expansion ◽  
Elevated Expression ◽  
Abnormal Metabolism ◽  
Proximal Tubular Epithelial Cells

Inflammation and abnormal metabolism play important roles in the pathogenesis of diabetic nephropathy (DN). Annexin A1 (ANXA1) contributes to inflammation resolution and improves metabolism. Here, we assess the effects of ANXA1 in diabetic mice and proximal tubular epithelial cells (PTECs) treated with high glucose plus palmitate acid (HGPA), and explore the association of ANXA1 with lipid accumulation in DN patients. It is found that ANXA1 deletion aggravates renal injuries, including albuminuria, mesangial matrix expansion and tubulointerstitial lesions in HFD/STZ-induced diabetic mice. ANXA1 deficiency promotes intra-renal lipid accumulation and drives mitochondrial alterations in kidneys. In addition, Ac2-26, an ANXA1 mimetic peptide, has a therapeutic effect against lipid toxicity in diabetic mice. In HGPA-treated human PTECs, <i>ANXA1</i> silencing causes FPR2/ALX-driven deleterious effects, which suppress phosphorylated Thr<sup>172</sup>AMPK, resulting in decreased PPARα and CPT1b expression and increased HGPA-induced lipid accumulation, apoptosis and elevated expression of pro-inflammatory and pro-fibrotic genes. Last but not least, the extent of lipid accumulation correlates with renal function, and the level of tubulointerstitial ANXA1 expression correlates with ectopic lipid deposition in kidneys of DN patients. These data demonstrate that ANXA1 regulates lipid metabolism of PTECs to ameliorate disease progression, hence it holds great potential as a therapeutic target for DN.

scholarly journals The Attenuation of Diabetic Nephropathy by Annexin A1 via Regulation of Lipid Metabolism through AMPK/PPARα/CPT1b Pathway

2021 ◽  
Author(s):  
Liang Wu ◽  
Changjie Liu ◽  
Dong-Yuan Chang ◽  
Rui Zhan ◽  
Mingming Zhao ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
Annexin A1 ◽  
Diabetic Mice ◽  
Tubulointerstitial Lesions ◽  
Matrix Expansion ◽  
Elevated Expression ◽  
Abnormal Metabolism ◽  
Proximal Tubular Epithelial Cells

Inflammation and abnormal metabolism play important roles in the pathogenesis of diabetic nephropathy (DN). Annexin A1 (ANXA1) contributes to inflammation resolution and improves metabolism. Here, we assess the effects of ANXA1 in diabetic mice and proximal tubular epithelial cells (PTECs) treated with high glucose plus palmitate acid (HGPA), and explore the association of ANXA1 with lipid accumulation in DN patients. It is found that ANXA1 deletion aggravates renal injuries, including albuminuria, mesangial matrix expansion and tubulointerstitial lesions in HFD/STZ-induced diabetic mice. ANXA1 deficiency promotes intra-renal lipid accumulation and drives mitochondrial alterations in kidneys. In addition, Ac2-26, an ANXA1 mimetic peptide, has a therapeutic effect against lipid toxicity in diabetic mice. In HGPA-treated human PTECs, <i>ANXA1</i> silencing causes FPR2/ALX-driven deleterious effects, which suppress phosphorylated Thr<sup>172</sup>AMPK, resulting in decreased PPARα and CPT1b expression and increased HGPA-induced lipid accumulation, apoptosis and elevated expression of pro-inflammatory and pro-fibrotic genes. Last but not least, the extent of lipid accumulation correlates with renal function, and the level of tubulointerstitial ANXA1 expression correlates with ectopic lipid deposition in kidneys of DN patients. These data demonstrate that ANXA1 regulates lipid metabolism of PTECs to ameliorate disease progression, hence it holds great potential as a therapeutic target for DN.

scholarly journals How does hepatic lipid accumulation lead to lipotoxicity in non-alcoholic fatty liver disease?

2021 ◽  
Vol 15 (1) ◽  
pp. 21-35
Author(s):  
Yana Geng ◽  
Klaas Nico Faber ◽  
Vincent E. de Meijer ◽  
Hans Blokzijl ◽  
Han Moshage
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Lipid Uptake ◽  
Cellular Mechanisms ◽  
Alcoholic Fatty Liver ◽  
Lipid Species ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD), characterized as excess lipid accumulation in the liver which is not due to alcohol use, has emerged as one of the major health problems around the world. The dysregulated lipid metabolism creates a lipotoxic environment which promotes the development of NAFLD, especially the progression from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH). Purposeand Aim This review focuses on the mechanisms of lipid accumulation in the liver, with an emphasis on the metabolic fate of free fatty acids (FFAs) in NAFLD and presents an update on the relevant cellular processes/mechanisms that are involved in lipotoxicity. The changes in the levels of various lipid species that result from the imbalance between lipolysis/lipid uptake/lipogenesis and lipid oxidation/secretion can cause organellar dysfunction, e.g. ER stress, mitochondrial dysfunction, lysosomal dysfunction, JNK activation, secretion of extracellular vesicles (EVs) and aggravate (or be exacerbated by) hypoxia which ultimately lead to cell death. The aim of this review is to provide an overview of how abnormal lipid metabolism leads to lipotoxicity and the cellular mechanisms of lipotoxicity in the context of NAFLD.

scholarly journals The Role of Lipids, Lipid Metabolism and Ectopic Lipid Accumulation in Axon Growth, Regeneration and Repair after CNS Injury and Disease

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1078
Author(s):  
Debasish Roy ◽  
Andrea Tedeschi
Keyword(s):  
Nervous System ◽  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
Axon Regeneration ◽  
Axon Growth ◽  
The Body ◽  
Cns Repair ◽  
Cord Injury ◽  
Cns Trauma

Axons in the adult mammalian nervous system can extend over formidable distances, up to one meter or more in humans. During development, axonal and dendritic growth requires continuous addition of new membrane. Of the three major kinds of membrane lipids, phospholipids are the most abundant in all cell membranes, including neurons. Not only immature axons, but also severed axons in the adult require large amounts of lipids for axon regeneration to occur. Lipids also serve as energy storage, signaling molecules and they contribute to tissue physiology, as demonstrated by a variety of metabolic disorders in which harmful amounts of lipids accumulate in various tissues through the body. Detrimental changes in lipid metabolism and excess accumulation of lipids contribute to a lack of axon regeneration, poor neurological outcome and complications after a variety of central nervous system (CNS) trauma including brain and spinal cord injury. Recent evidence indicates that rewiring lipid metabolism can be manipulated for therapeutic gain, as it favors conditions for axon regeneration and CNS repair. Here, we review the role of lipids, lipid metabolism and ectopic lipid accumulation in axon growth, regeneration and CNS repair. In addition, we outline molecular and pharmacological strategies to fine-tune lipid composition and energy metabolism in neurons and non-neuronal cells that can be exploited to improve neurological recovery after CNS trauma and disease.

Regulation of Renal Lipid Metabolism, Lipid Accumulation, and Glomerulosclerosis in FVBdb/db Mice With Type 2 Diabetes

Diabetes ◽  
2005 ◽  
Vol 54 (8) ◽  
pp. 2328-2335 ◽  
Author(s):  
Z. Wang ◽  
T. Jiang ◽  
J. Li ◽  
G. Proctor ◽  
J. L. McManaman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Lipid Metabolism ◽  
Lipid Accumulation

scholarly journals Hepatic Lipid Accumulation Induced by a High-fat Diet Is Regulated by Nrf2 Through Multiple Pathways

2021 ◽  
Author(s):  
sheng Qiu ◽  
Zerong Liang ◽  
Qinan Wu ◽  
Miao Wang ◽  
Mengliu Yang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Underlying Mechanism ◽  
Luciferase Assay ◽  
High Fat ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Abstract BackgroundNuclear factor erythroid 2-related factor 2 (Nrf2) is reportedly involved in hepatic lipid metabolism, but the results are contradictory and the underlying mechanism thus remains unclear. Herein we focused on elucidating the effects of Nrf2 on hepatic adipogenesis and on determining the possible underlying mechanism. We established a metabolic associated fatty liver disease (MAFLD) model in high fat diet (HFD) fed Nrf2 knockout (Nrf2 KO) mice; further, a cell model of lipid accumulation was established using mouse primary hepatocytes (MPHs) treated with free fatty acids (FAs). Using these models, we investigated the relationship between Nrf2 and autophagy and its role in the development of MAFLD.ResultsWe observed that Nrf2 expression levels were up-regulated in patients with MAFLD and diet-induced obese mice. Nrf2 deficiency led to hepatic lipid accumulation in vivo and in vitro, in addition to, promoting lipogenesis mainly by increasing SREBP-1 activity. Moreover, Nrf2 deficiency attenuated autophagic flux and inhibited the fusion of autophagosomes and lysosomes in vivo and in vitro. Weakened autophagy caused reduced lipolysis in the liver. Importantly, Chromatin immunoprecipitation-qPCR (ChIP-qPCR) and dual-luciferase assay results proved that Nrf2 bound to LAMP1 promoter and regulated its transcriptional activity. We accordingly report that Nrf2-LAMP1 interaction has an indispensable role in Nrf2-regulated hepatosteatosis. ConclusionsThese data collectively confirm that Nrf2 deficiency promotes hepatosteatosis by enhancing SREBP-1 activity and attenuating autophagy. To conclude, our data reveal a novel multi-pathway effect of Nrf2 on lipid metabolism in the liver, and we believe that multi-target intervention of Nrf2 signaling is a promising new strategy for the prevention and treatment of MAFLD.

scholarly journals Intramyocellular Lipid Accumulation After High-Fat Diet Is Associated with the Gene Expression Involved in Lipid Metabolism in Skeletal Muscle of Non-Obese Men

2016 ◽  
Vol 62 (Suppl.1) ◽  
pp. 144-145
Author(s):  
SAORI KAKEHI ◽  
YOSHIFUMI TAMURA ◽  
KAGEUMI TAKENO ◽  
YUKO SAKURAI ◽  
MINAKO KAWAGUCHI ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Intramyocellular Lipid ◽  
High Fat
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