Loss of biliverdin reductase-A (BVRA) promotes lipid accumulation and lipotoxicity in mouse proximal tubule cells.

Loss of biliverdin reductase-A (BVRA) promotes lipid accumulation and lipotoxicity in mouse proximal tubule cells. Am J Physiol Renal Physiol. 2018 Apr 04;: Authors: Adeosun SO, Gordon DM, Weeks MF, Moore KH, Hall JE, Hinds TD, Stec DE Abstract Obesity and increased lipid availability have been implicated in the development and progression of chronic kidney disease. One of the major sites of renal lipid accumulation is in the proximal tubule cells of the kidney, suggesting that these cells may be susceptible to lipotoxicity. We previously demonstrated that loss of hepatic BVRA causes fat accumulation in livers of mice on a high-fat diet. To determine the role of BVRA in mouse proximal tubule cells, we generated a CRISPR targeting BVRA for a knock-out in mouse MCT proximal tubule cells (BVRA KO). The BVRA-KO cells had significantly less metabolic potential and mitochondrial respiration, which was exacerbated by treatment with saturated fatty acid, palmitic acid. The BVRA KO cells also showed increased intracellular triglycerides which were associated with increased fatty acid uptake gene cluster of differentiation 36 (CD36) as well as increased de novo lipogenesis as measured by higher neutral lipids. Additionally, NGAL1 expression, Annexin-v FITC staining, and LDH assays all demonstrated that BVRA KO cells are more sensitive to palmitic acid-induced lipotoxicity than wild-type cells. Phosphorylation of AKT and BAD, which play a role in cell survival path...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

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In conclusions, the present findings firstly supported that renal KLF4 played an important role in combating obesity-related nephropathy, and KLF4/mitochondrial function partially determined the energy homeostasis in chronic kidney diseases. PMID: 31800161 [PubMed - as supplied by publisher]
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
In conclusion, our findings link the calcification of the vascular tissue with the expression of FGF23 in the vessels and with the elevation of circulating levels this hormone. Permanently Boosting Levels of Natural Killer Cells in Mice to Increase Cancer Resistance https://www.fightaging.org/archives/2019/09/permanently-boosting-levels-of-natural-killer-cells-in-mice-to-increase-cancer-resistance/ Researchers here demonstrate a very interesting approach to immunotherapy: they introduce engineered stem cells in mice that will give rise to additional natural killer T cells, boosting the capability of the ...
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Discussion of Developmental Effects on Aging Microtubule Function and Longevity in Nematodes Quantifying the Correlation Between Poverty and Faster Pace of Aging Matthew O'Connor Presenting on Underdog Pharmaceuticals at Undoing Aging 2019 https://www.fightaging.org/archives/2019/09/matthew-oconnor-presenting-on-underdog-pharmaceuticals-at-undoing-aging-2019/ Here Matthew O'Connor of the SENS Research Foundation talks about the research that led to founding of Underdog Pharmaceuticals, a biotech startup incubated by the foundation to commercialize a means of targeting 7-ketocholesterol in atheroscleros...
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Publication date: Available online 20 September 2019Source: Redox BiologyAuthor(s): Mercedes Muñoz, Maria Elvira López-Oliva, Claudia Rodríguez, María Pilar Martínez, Javier Sáenz-Medina, Ana Sánchez, Belén Climent, Sara Benedito, Albino García-Sacristán, Luis Rivera, Medardo Hernández, Dolores PrietoAbstractOxidative stress-associated endothelial dysfunction is a key pathogenic factor underlying the microvascular complications of metabolic disease. NADPH oxidase (Nox) is a major source of oxidative stress in diabetic nephropathy and chronic kidne...
Source: Redox Biology - Category: Biology Source Type: research
We examined human lung tissue from COPD patients and normal control subjects, and found a substantial increase in p16-expressing alveolar cells in COPD patients. Using a transgenic mouse deficient for p16, we demonstrated that lungs of mice lacking p16 were structurally and functionally resistant to CS-induced emphysema due to activation of IGF1/Akt regenerative and protective signaling. Fat Tissue Surrounds Skeletal Muscle to Accelerate Atrophy in Aging and Obesity https://www.fightaging.org/archives/2019/09/fat-tissue-surrounds-skeletal-muscle-to-accelerate-atrophy-in-aging-and-obesity/ Researchers her...
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Abstract Obesity, as well as the metabolic syndrome, are well known risk factors for chronic kidney disease (CKD), but less is known about the mechanism(s) by which metabolic syndrome might accelerate kidney disease. We hypothesized that metabolic syndrome should accelerate the development of kidney disease and that it might be associated with alterations in energy metabolism.We studied the pound mouse (which develops early metabolic syndrome due to a leptin receptor deletion) and wild type littermates and compared the level of renal injury and muscle wasting following equivalent injury with oral adenine. Renal fu...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research
We examined 9293 individuals from the Copenhagen General Population Study using nuclear magnetic resonance spectroscopy measurements of total cholesterol, free- and esterified cholesterol, triglycerides, phospholipids, and particle concentration. Fourteen subclasses of decreasing size and their lipid constituents were analysed: six subclasses were very low-density lipoprotein (VLDL), one intermediate-density lipoprotein (IDL), three low-density lipoprotein (LDL), and four subclasses were high-density lipoprotein (HDL). Remnant lipoproteins were VLDL and IDL combined. Mean nonfasting cholesterol concentration was 72...
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In this study we show, for the first time, significant alterations in cholesterol efflux capacity in adolescents throughout the range of BMI, a relationship between six circulating adipocyte-derived EVs microRNAs targeting ABCA1 and cholesterol efflux capacity, and in vitro alterations of cholesterol efflux in macrophages exposed to visceral adipose tissue adipocyte-derived EVs acquired from human subjects. These results suggest that adipocyte-derived EVs, and their microRNA content, may play a critical role in the early pathological development of ASCVD. Commentary on the Developing UK Government Position on Hea...
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Dominique E. Martin1,2, Amanda K. Jones1,3, Sambhu M. Pillai1,4, Maria L. Hoffman1,5, Katelyn K. McFadden1,6, Steven A. Zinn1, Kristen E. Govoni1 and Sarah A. Reed1* 1Department of Animal Science, University of Connecticut, Storrs, CT, United States 2Department of Psychology, Providence College, Providence, RI, United States 3Department of Pediatrics, School of Medicine, University of Colorado, Aurora, Aurora, CO, United States 4School of Medicine, Georgetown University, Washington, DC, United States 5Department of Fisheries, Animal and Veterinary Sciences, The University of Rhode Island, Kingston, RI, United St...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
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