scholarly journals Peroxisomal Disorders and Their Mouse Models Point to Essential Roles of Peroxisomes for Retinal Integrity

2021 ◽  
Vol 22 (8) ◽  
pp. 4101
Author(s):  
Yannick Das ◽  
Daniëlle Swinkels ◽  
Myriam Baes
Keyword(s):  
Mouse Models ◽  
Current Knowledge ◽  
Lipid Synthesis ◽  
Ether Lipid ◽  
Metabolic Disturbances ◽  
Peroxisomal Disorders ◽  
Biochemical Alterations ◽  
Ocular Symptoms ◽  
Peroxisomal Biogenesis ◽  
Fatty Acid Accumulation

Peroxisomes are multifunctional organelles, well known for their role in cellular lipid homeostasis. Their importance is highlighted by the life-threatening diseases caused by peroxisomal dysfunction. Importantly, most patients suffering from peroxisomal biogenesis disorders, even those with a milder disease course, present with a number of ocular symptoms, including retinopathy. Patients with a selective defect in either peroxisomal α- or β-oxidation or ether lipid synthesis also suffer from vision problems. In this review, we thoroughly discuss the ophthalmological pathology in peroxisomal disorder patients and, where possible, the corresponding animal models, with a special emphasis on the retina. In addition, we attempt to link the observed retinal phenotype to the underlying biochemical alterations. It appears that the retinal pathology is highly variable and the lack of histopathological descriptions in patients hampers the translation of the findings in the mouse models. Furthermore, it becomes clear that there are still large gaps in the current knowledge on the contribution of the different metabolic disturbances to the retinopathy, but branched chain fatty acid accumulation and impaired retinal PUFA homeostasis are likely important factors.

Ether lipid synthesis and its deficiency in peroxisomal disorders

Biochimie ◽  
1993 ◽  
Vol 75 (3-4) ◽  
pp. 183-189 ◽  
Author(s):  
H. van den Bosch ◽  
G. Schrakamp ◽  
D. Hardeman ◽  
A.W.M. Zomer ◽  
R.J.A. Wanders ◽  
...  
Keyword(s):  
Lipid Synthesis ◽  
Ether Lipid ◽  
Peroxisomal Disorders

Abstract 577: MicroRNA-30c Reduces Plasma Cholesterol in Different Hypercholesterolemic and Hyperglycemic Mouse Models

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Sara Irani ◽  
Jahangir Iqbal ◽  
M.Mahmood Hussain
Keyword(s):  
Mouse Models ◽  
Metabolic Disorders ◽  
Leptin Receptor ◽  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Lipid Synthesis ◽  
Density Lipoprotein ◽  
High Plasma ◽  
Western Diet ◽  
Lower Plasma

High plasma cholesterol levels are found in several metabolic disorders and their reductions are advocated to reduce risk of atherosclerosis. A way to lower plasma lipids is to curtail lipoprotein assembly and secretion; however, this is associated with steatosis. We have shown that microRNA-30c (miR-30c) reduces Western diet-induced hypercholesterolemia and atherosclerosis in C57BL/6J and Apoe -/- mice with no obvious adverse effects by reducing hepatic lipoprotein production and lipid synthesis. Here, we tested the effect of miR-30c on plasma lipids, transaminases and hepatic lipids in five different mouse models. Hepatic delivery of miR-30c reduced MTP activity but did not affect plasma cholesterol, triglyceride and glucose in chow-fed C57Bl6J and streptozotocin-induced diabetic, normolipidemic mice. However, hepatic delivery of miR-30c to chow fed leptin deficient ( ob/ob ) and leptin receptor deficient ( db/db ) hypercholesterolemic and hyperglycemic type 2 diabetic mice reduced cholesterol in total plasma and VLDL/LDL by ~ 28%and ~ 25%, respectively, without affecting phospholipid, triglyceride and glucose levels. Interestingly, these mice had lower plasma transaminases and creatine kinases indicating possible beneficial effects. Mechanistic studies showed that miR-30c reduced hepatic MTP activity and lipid synthesis. Moreover, miR-30c significantly lowered plasma cholesterol and atherosclerosis in Western-diet fed low density lipoprotein receptor knockout mice with no effect on plasma triglyceride, glucose and transaminases, suggesting that miR-30c can be a potential therapeutic agent for homozygous familial hypercholesterolemia. In all these studies, hepatic lipid levels were similar in control and miR-30c injected mice. These studies indicate that miR-30c reduces plasma cholesterol in diet-induced and diabetic hyperholesterolemic mice but not in normocholesterolemic mice. Thus, miR-30c may be beneficial in lowering plasma cholesterol in different metabolic disorders independent of the origin of hypercholesterolemia.

Essential fatty acids and serine as plasmalogen precursors in relation to competing metabolic pathways

1991 ◽  
Vol 69 (7) ◽  
pp. 475-484 ◽  
Author(s):  
Harold W. Cook ◽  
Susan E. Thomas ◽  
Zhaolin Xu
Keyword(s):  
Fatty Acids ◽  
Vascular Tissue ◽  
Essential Fatty Acids ◽  
Ether Lipid ◽  
Water Soluble ◽  
Peroxisomal Disorders ◽  
Ethanolamine Phosphoglycerides ◽  
Acyl Chains ◽  
Cellular Water ◽  
Soluble Components

Interest in altered ether-lipid metabolism, associated with peroxisomal disorders including adrenoleukodystrophy and Zellweger's syndrome, has highlighted present limitations in our understanding of the biosynthesis and turnover of plasmalogens. These 1-alkenyl ethanolamine phosphoglycerides are major phospholipids in brain, vascular tissue, neutrophils, and most tumors, and they constitute 15–20% of total phospholipids in cultured glioma cells. In glioma, turnover of polyunsaturated acyl chains in the sn-2 position of plasmalogens was examined in relation to selectivity for the (n–3) and (n–6) families. Remodeling of acyl chains was more dependent on chain length than on selectivity between families, consistent with plasmalogens enriched in polyunsaturated, but not specifically (n–3), fatty acids. Extracellular serine was a precursor of serine and ethanolamine phosphoglycerides and was associated with plasmalogens due to decarboxylation and headgroup exchange. Incorporation of extracellular serine ceased within 8 h, even though more than 50% of the label remained in the medium. Analyses of medium and cellular water-soluble components indicated rapid conversion of serine to glycine and other metabolites not used in phospholipid biosynthesis. Thus, nutrient molecules as precursors of plasmalogens are involved in complex competitive interactions. As functions of plasmalogens are clarified, regulation of plasmalogen turnover becomes an increasingly important issue and elucidation of these processes is essential.Key words: plasmalogen, serine, fatty acids, glioma.

scholarly journals Renal stone disease: causes, evaluation and medical treatment

2006 ◽  
Vol 50 (4) ◽  
pp. 823-831 ◽  
Author(s):  
Ita Pfeferman Heilberg ◽  
Nestor Schor
Keyword(s):  
Medical Treatment ◽  
Renal Stone ◽  
Salt Intake ◽  
Current Knowledge ◽  
Stone Formation ◽  
Potassium Citrate ◽  
Blood Analysis ◽  
Dietary Recommendations ◽  
Metabolic Disturbances ◽  
Mineral Density

The purpose of the present review is to provide an update about the most common risk factors or medical conditions associated with renal stone formation, the current methods available for metabolic investigation, dietary recommendations and medical treatment. Laboratory investigation of hypercalciuria, hyperuricosuria, hyperoxaluria, cystinuria, hypocitraturia, renal tubular acidosis, urinary tract infection and reduction of urinary volume is based on the results of 24-hr urine collection and a spot urine for urinary sediment, culture and pH. Blood analysis for creatinine, calcium and uric acid must be obtained. Bone mineral density has to be determined mainly among hypercalciurics and primary hyperparathyroidism has to be ruled out. Current knowledge does not support calcium restriction recommendation because it can lead to secondary hyperoxaluria and bone demineralization. Reduction of animal protein and salt intake, higher fluid intake and potassium consumption should be implemented. Medical treatments involve the use of thiazides, allopurinol, potassium citrate or other drugs according to the metabolic disturbances. The correction of those metabolic abnormalities is the basic tool for prevention or reduction of recurrent stone formation.

scholarly journals Genetic Mouse Models as In Vivo Tools for Cholangiocarcinoma Research

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1868 ◽  
Author(s):  
Oihane Erice ◽  
Adrian Vallejo ◽  
Mariano Ponz-Sarvise ◽  
Michael Saborowski ◽  
Arndt Vogel ◽  
...  
Keyword(s):  
Mouse Models ◽  
Molecular Mechanisms ◽  
Complex Disease ◽  
Current Knowledge ◽  
Genetic Alterations ◽  
In Vivo Model ◽  
In Vivo Models ◽  
Dismal Prognosis ◽  
Genetic Mouse Models

Cholangiocarcinoma (CCA) is a genetically and histologically complex disease with a highly dismal prognosis. A deeper understanding of the underlying cellular and molecular mechanisms of human CCA will increase our current knowledge of the disease and expedite the eventual development of novel therapeutic strategies for this fatal cancer. This endeavor is effectively supported by genetic mouse models, which serve as sophisticated tools to systematically investigate CCA pathobiology and treatment response. These in vivo models feature many of the genetic alterations found in humans, recapitulate multiple hallmarks of cholangiocarcinogenesis (encompassing cell transformation, preneoplastic lesions, established tumors and metastatic disease) and provide an ideal experimental setting to study the interplay between tumor cells and the surrounding stroma. This review is intended to serve as a compendium of CCA mouse models, including traditional transgenic models but also genetically flexible approaches based on either the direct introduction of DNA into liver cells or transplantation of pre-malignant cells, and is meant as a resource for CCA researchers to aid in the selection of the most appropriate in vivo model system.

scholarly journals Premature Ovarian Insufficiency: New Perspectives on Genetic Cause and Phenotypic Spectrum

2016 ◽  
Vol 37 (6) ◽  
pp. 609-635 ◽  
Author(s):  
Elena J. Tucker ◽  
Sonia R. Grover ◽  
Anne Bachelot ◽  
Philippe Touraine ◽  
Andrew H. Sinclair
Keyword(s):  
Mouse Models ◽  
Genetic Basis ◽  
Current Knowledge ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Activity ◽  
Substantial Evidence ◽  
Ovarian Insufficiency ◽  
Phenotypic Spectrum ◽  
Disease Mechanisms

Abstract Premature ovarian insufficiency (POI) is one form of female infertility, defined by loss of ovarian activity before the age of 40 and characterized by amenorrhea (primary or secondary) with raised gonadotropins and low estradiol. POI affects up to one in 100 females, including one in 1000 before the age of 30. Substantial evidence suggests a genetic basis for POI; however, the majority of cases remain unexplained, indicating that genes likely to be associated with this condition are yet to be discovered. This review discusses the current knowledge of the genetic basis of POI. We highlight genes typically known to cause syndromic POI that can be responsible for isolated POI. The role of mouse models in understanding POI pathogenesis is discussed, and a thorough list of candidate POI genes is provided. Identifying a genetic basis for POI has multiple advantages, such as enabling the identification of presymptomatic family members who can be offered counseling and cryopreservation of eggs before depletion, enabling personalized treatment based on the cause of an individual's condition, and providing better understanding of disease mechanisms that ultimately aid the development of improved treatments.

scholarly journals Black elderberry extract attenuates inflammation and metabolic dysfunction in diet-induced obese mice

2015 ◽  
Vol 114 (8) ◽  
pp. 1123-1131 ◽  
Author(s):  
Nicholas J. Farrell ◽  
Gregory H. Norris ◽  
Julia Ryan ◽  
Caitlin M. Porter ◽  
Christina Jiang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Fatty Acid Synthase ◽  
Transforming Growth Factor ◽  
Serum Insulin ◽  
Lipid Synthesis ◽  
Metabolic Effects ◽  
Liver Cholesterol ◽  
Model Assessment ◽  
Metabolic Disturbances ◽  
Monocyte Chemoattractant Protein 1

AbstractDietary anthocyanins have been shown to reduce inflammation in animal models and may ameliorate obesity-related complications. Black elderberry is one of the richest sources of anthocyanins. We investigated the metabolic effects of anthocyanin-rich black elderberry extract (BEE) in a diet-induced obese C57BL/6J mouse model. Mice were fed either a low-fat diet (n 8), high-fat lard-based diet (HFD; n 16), HFD+0·25 % (w/w) BEE (0·25 %-BEE; n 16) or HFD+1·25 % BEE (1·25 %-BEE; n 16) for 16 weeks. The 0·25 % BEE (0·034 % anthocyanin, w/w) and 1·25 % BEE (0·17 % anthocyanin, w/w) diets corresponded to estimated anthocyanin doses of 20–40 mg and 100–200 mg per kg of body weight, respectively. After 16 weeks, both BEE groups had significantly lower liver weights, serum TAG, homoeostasis model assessment and serum monocyte chemoattractant protein-1 compared with HFD. The 0·25 %-BEE also had lower serum insulin and TNFα compared with HFD. Hepatic fatty acid synthase mRNA was lower in both BEE groups, whereas PPARγ2 mRNA and liver cholesterol were lower in 1·25 %-BEE, suggesting decreased hepatic lipid synthesis. Higher adipose PPARγ mRNA, transforming growth factor β mRNA and adipose tissue histology suggested a pro-fibrogenic phenotype that was less inflammatory in 1·25 %-BEE. Skeletal muscle mRNA expression of the myokine IL-6 was higher in 0·25 %-BEE relative to HFD. These results suggest that BEE may have improved some metabolic disturbances present in this mouse model of obesity by lowering serum TAG, inflammatory markers and insulin resistance.

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