Lipid Storage Disorders: Biological and Medical Aspects


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Cell , FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46 , Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Brown and beige fat: molecular parts of a thermogenic machine. Diabetes 64 , Adipsin: a circulating serine protease homolog secreted by adipose tissue and sciatic nerve. Science , Identification and importance of brown adipose tissue in adult humans.

N Engl J Med , Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat. Nat Med 19 , Cell Metab 21 , Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med 15 , Genes Dev 26 , J Biol Chem , Lipodystrophies: genetic and acquired body fat disorders. J Clin Endocrinol Metab 96 , Effect of CL,, a thermogenic beta 3-agonist, on energy balance and brown and white adipose tissues in rats. Am J Physiol , RR Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes.

Central role of tumor necrosis-alpha.

J Clin Invest 94 , Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. A classical brown adipose tissue mRNA signature partly overlaps with brite in the supraclavicular region of adult humans.

New strategies for the treatment of lysosomal storage diseases (Review)

Cell Metab 17 , Disruption of hypoxia-inducible factor 1 in adipocytes improves insulin sensitivity and decreases adiposity in high-fat diet-fed mice. Diabetes 60 , Brown and beige fat: physiological roles beyond heat generation. Cell Metab 22 , Immunological complications of obesity. Nat Immunol 13 , A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat.

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Selective parasympathetic innervation of subcutaneous and intra-abdominal fat—functional implications. Activated type 2 innate lymphoid cells regulate beige fat biogenesis. Inducible lineage tracing of Pax7-descendant cells reveals embryonic origin of adult satellite cells. Genesis 48 , Evidence for two types of brown adipose tissue in humans. A smooth muscle-like origin for beige adipocytes.

Cell Metab 19 , Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. White adipocyte vascular endothelial growth factor: regulation by insulin. Due to the success of these animal trials, a small scale clinical trial showed a small but non-significant improvement Clearly there are safety issues with using viruses as gene delivery targets. Interestingly, autophagy enhancers such as lithium and L, inositol monophosphatase inhibitors 67 were shown to reduce the abnormal accumulation of autophagosomes, mitochondrial ATP synthase subunit C and lipofuscin in Cln3 mutant knock-in cerebellar cells This study points to the need for a deeper understanding of the mechanisms of defective autophagy and its therapeutic application in NCL.

Metabolic Disorders

Fabry disease GLA alpha- galactosidase A Homodimeric glycoprotein, hydrolyses glycolipids and glycoproteins Failure to catabolize alpha-D-galactosyl glycolipid moieties Inhibition caused disruption autophagy-lysosome pathway by of , Gaucher disease GBA glucosidase, beta, acid Lysosomal membrane protein, Involved in glycolipid metabolism Accumulation of glucocerebrosides Block in autophagic flux , Glycogenoses GAA acid alpha-glucosidase Lysosomal enzyme, converts glycogen to glucose Glycogen accumulation Accumulation autophagosomes of , Mucopolysaccharidoses More than 10 genes identified Lysosomal enzymes Glycosaminoglycans Defective autophagosome-lysosome fusion While in recent years an important role of autophagy in the maintenance of lipo-homeostasis has been revealed, the contribution of autophagy pathways to the pathology in many lipid storage disorders still remains poorly understood.

Further work will be required to better define the mechanistic details of autophagy perturbations in each specific disease and their contribution to the pathology. These studies will undoubtedly inform new treatment strategies as has already been demonstrated in case of several lipid storage disorders. De Duve, C. Annual review of physiology 28, Lamb, C. Nature reviews. Molecular cell biology 14, Ravikumar, B.

Lysosome Storage Disorders Made Simple!

Nature cell biology 12, Yla-Anttila, P. Autophagy 5, Hailey, D.


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Lysosomal Storage Disorders: Treatments - Medical Clinical Policy Bulletins | Aetna

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Lipid Storage Disorders: Biological and Medical Aspects Lipid Storage Disorders: Biological and Medical Aspects
Lipid Storage Disorders: Biological and Medical Aspects Lipid Storage Disorders: Biological and Medical Aspects
Lipid Storage Disorders: Biological and Medical Aspects Lipid Storage Disorders: Biological and Medical Aspects
Lipid Storage Disorders: Biological and Medical Aspects Lipid Storage Disorders: Biological and Medical Aspects
Lipid Storage Disorders: Biological and Medical Aspects Lipid Storage Disorders: Biological and Medical Aspects
Lipid Storage Disorders: Biological and Medical Aspects Lipid Storage Disorders: Biological and Medical Aspects
Lipid Storage Disorders: Biological and Medical Aspects Lipid Storage Disorders: Biological and Medical Aspects

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