Kumari M

References (7)

Title : Role of Endothelial Cell Lipoprotein Lipase for Brown Adipose Tissue Lipid and Glucose Handling - Thiemann_2022_Front.Physiol_13_859671
Author(s) : Thiemann E , Schwaerzer GK , Evangelakos I , Fuh MM , Jaeckstein MY , Behrens J , Nilsson SK , Kumari M , Scheja L , Pfeifer A , Heeren J , Heine M
Ref : Front Physiol , 13 :859671 , 2022
Abstract : Cold-induced activation of brown adipose tissue (BAT) has an important impact on systemic lipoprotein metabolism by accelerating the processing of circulating triglyceride-rich lipoproteins (TRL). Lipoprotein lipase (LPL) expressed by adipocytes is translocated via endothelial to the capillary lumen, where LPL acts as the central enzyme for the vascular lipoprotein processing. Based on preliminary data showing that LPL is not only expressed in adipocytes but also in endothelial cells of cold-activated BAT, we aimed to dissect the relevance of endothelial versus adipocyte LPL for lipid and energy metabolism in the context of adaptive thermogenesis. By metabolic studies we found that cold-induced triglyceride uptake into BAT, lipoprotein disposal, glucose uptake and adaptive thermogenesis were not impaired in mice lacking Lpl exclusively in endothelial cells. This finding may be explained by a compensatory upregulation in the expression of adipocyte-derived Lpl and endothelial lipase (Lipg).
ESTHER : Thiemann_2022_Front.Physiol_13_859671
PubMedSearch : Thiemann_2022_Front.Physiol_13_859671
PubMedID: 35422714

Title : Aging. Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans - Folick_2015_Science_347_83
Author(s) : Folick A , Oakley HD , Yu Y , Armstrong EH , Kumari M , Sanor L , Moore DD , Ortlund EA , Zechner R , Wang MC
Ref : Science , 347 :83 , 2015
Abstract : Lysosomes are crucial cellular organelles for human health that function in digestion and recycling of extracellular and intracellular macromolecules. We describe a signaling role for lysosomes that affects aging. In the worm Caenorhabditis elegans, the lysosomal acid lipase LIPL-4 triggered nuclear translocalization of a lysosomal lipid chaperone LBP-8, which promoted longevity by activating the nuclear hormone receptors NHR-49 and NHR-80. We used high-throughput metabolomic analysis to identify several lipids in which abundance was increased in worms constitutively overexpressing LIPL-4. Among them, oleoylethanolamide directly bound to LBP-8 and NHR-80 proteins, activated transcription of target genes of NHR-49 and NHR-80, and promoted longevity in C. elegans. These findings reveal a lysosome-to-nucleus signaling pathway that promotes longevity and suggest a function of lysosomes as signaling organelles in metazoans.
ESTHER : Folick_2015_Science_347_83
PubMedSearch : Folick_2015_Science_347_83
PubMedID: 25554789
Gene_locus related to this paper: caeel-K04A8.5

Title : Curcumin-Loaded Nanoparticles Potently Induce Adult Neurogenesis and Reverse Cognitive Deficits in Alzheimer's Disease Model via Canonical Wnt\/beta-Catenin Pathway - Tiwari_2014_ACS.Nano_8_76
Author(s) : Tiwari SK , Agarwal S , Seth B , Yadav A , Nair S , Bhatnagar P , Karmakar M , Kumari M , Chauhan LK , Patel DK , Srivastava V , Singh D , Gupta SK , Tripathi A , Chaturvedi RK , Gupta KC
Ref : ACS Nano , 8 :76 , 2014
Abstract : Neurogenesis, a process of generation of new neurons, is reported to be reduced in several neurodegenerative disorders including Alzheimer's disease (AD). Induction of neurogenesis by targeting endogenous neural stem cells (NSC) could be a promising therapeutic approach to such diseases by influencing the brain self-regenerative capacity. Curcumin, a neuroprotective agent, has poor brain bioavailability. Herein, we report that curcumin-encapsulated PLGA nanoparticles (Cur-PLGA-NPs) potently induce NSC proliferation and neuronal differentiation in vitro and in the hippocampus and subventricular zone of adult rats, as compared to uncoated bulk curcumin. Cur-PLGA-NPs induce neurogenesis by internalization into the hippocampal NSC. Cur-PLGA-NPs significantly increase expression of genes involved in cell proliferation (reelin, nestin, and Pax6) and neuronal differentiation (neurogenin, neuroD1, neuregulin, neuroligin, and Stat3). Curcumin nanoparticles increase neuronal differentiation by activating the Wnt/beta-catenin pathway, involved in regulation of neurogenesis. These nanoparticles caused enhanced nuclear translocation of beta-catenin, decreased GSK-3beta levels, and increased promoter activity of the TCF/LEF and cyclin-D1. Pharmacological and siRNA-mediated genetic inhibition of the Wnt pathway blocked neurogenesis-stimulating effects of curcumin. These nanoparticles reverse learning and memory impairments in an amyloid beta induced rat model of AD-like phenotypes, by inducing neurogenesis. In silico molecular docking studies suggest that curcumin interacts with Wif-1, Dkk, and GSK-3beta. These results suggest that curcumin nanoparticles induce adult neurogenesis through activation of the canonical Wnt/beta-catenin pathway and may offer a therapeutic approach to treating neurodegenerative diseases such as AD, by enhancing a brain self-repair mechanism.
ESTHER : Tiwari_2014_ACS.Nano_8_76
PubMedSearch : Tiwari_2014_ACS.Nano_8_76
PubMedID: 24467380

Title : Adiponutrin functions as a nutritionally regulated lysophosphatidic acid acyltransferase - Kumari_2012_Cell.Metab_15_691
Author(s) : Kumari M , Schoiswohl G , Chitraju C , Paar M , Cornaciu I , Rangrez AY , Wongsiriroj N , Nagy HM , Ivanova PT , Scott SA , Knittelfelder O , Rechberger GN , Birner-Gruenberger R , Eder S , Brown HA , Haemmerle G , Oberer M , Lass A , Kershaw EE , Zimmermann R , Zechner R
Ref : Cell Metab , 15 :691 , 2012
Abstract : Numerous studies in humans link a nonsynonymous genetic polymorphism (I148M) in adiponutrin (ADPN) to various forms of fatty liver disease and liver cirrhosis. Despite its high clinical relevance, the molecular function of ADPN and the mechanism by which I148M variant affects hepatic metabolism are unclear. Here we show that ADPN promotes cellular lipid synthesis by converting lysophosphatidic acid (LPA) into phosphatidic acid. The ADPN-catalyzed LPA acyltransferase (LPAAT) reaction is specific for LPA and long-chain acyl-CoAs. Wild-type mice receiving a high-sucrose diet exhibit substantial upregulation of Adpn in the liver and a concomitant increase in LPAAT activity. In Adpn-deficient mice, this diet-induced increase in hepatic LPAAT activity is reduced. Notably, the I148M variant of human ADPN exhibits increased LPAAT activity leading to increased cellular lipid accumulation. This gain of function provides a plausible biochemical mechanism for the development of liver steatosis in subjects carrying the I148M variant.
ESTHER : Kumari_2012_Cell.Metab_15_691
PubMedSearch : Kumari_2012_Cell.Metab_15_691
PubMedID: 22560221

Title : Growth retardation, impaired triacylglycerol catabolism, hepatic steatosis, and lethal skin barrier defect in mice lacking comparative gene identification-58 (CGI-58) - Radner_2010_J.Biol.Chem_285_7300
Author(s) : Radner FP , Streith IE , Schoiswohl G , Schweiger M , Kumari M , Eichmann TO , Rechberger G , Koefeler HC , Eder S , Schauer S , Theussl HC , Preiss-Landl K , Lass A , Zimmermann R , Hoefler G , Zechner R , Haemmerle G
Ref : Journal of Biological Chemistry , 285 :7300 , 2010
Abstract : Comparative gene identification-58 (CGI-58), also designated as alpha/beta-hydrolase domain containing-5 (ABHD-5), is a lipid droplet-associated protein that activates adipose triglyceride lipase (ATGL) and acylates lysophosphatidic acid. Activation of ATGL initiates the hydrolytic catabolism of cellular triacylglycerol (TG) stores to glycerol and nonesterified fatty acids. Mutations in both ATGL and CGI-58 cause "neutral lipid storage disease" characterized by massive accumulation of TG in various tissues. The analysis of CGI-58-deficient (Cgi-58(-/-)) mice, presented in this study, reveals a dual function of CGI-58 in lipid metabolism. First, systemic TG accumulation and severe hepatic steatosis in newborn Cgi-58(-/-) mice establish a limiting role for CGI-58 in ATGL-mediated TG hydrolysis and supply of nonesterified fatty acids as energy substrate. Second, a severe skin permeability barrier defect uncovers an essential ATGL-independent role of CGI-58 in skin lipid metabolism. The neonatal lethal skin barrier defect is linked to an impaired hydrolysis of epidermal TG. As a consequence, sequestration of fatty acids in TG prevents the synthesis of acylceramides, which are essential lipid precursors for the formation of a functional skin permeability barrier. This mechanism may also underlie the pathogenesis of ichthyosis in neutral lipid storage disease patients lacking functional CGI-58.
ESTHER : Radner_2010_J.Biol.Chem_285_7300
PubMedSearch : Radner_2010_J.Biol.Chem_285_7300
PubMedID: 20023287
Gene_locus related to this paper: mouse-abhd5

Title : PLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10 494 cases and 15 624 controls of European Ancestry - Casas_2010_Circulation_121_2284
Author(s) : Casas JP , Ninio E , Panayiotou A , Palmen J , Cooper JA , Ricketts SL , Sofat R , Nicolaides AN , Corsetti JP , Fowkes FG , Tzoulaki I , Kumari M , Brunner EJ , Kivimaki M , Marmot MG , Hoffmann MM , Winkler K , Marz W , Ye S , Stirnadel HA , Boekholdt SM , Khaw KT , Humphries SE , Sandhu MS , Hingorani AD , Talmud PJ
Ref : Circulation , 121 :2284 , 2010
Abstract : BACKGROUND: Higher lipoprotein-associated phospholipase A(2)(Lp-PLA2) activity is associated with increased risk of coronary heart disease (CHD), making Lp-PLA2 a potential therapeutic target. PLA2G7 variants associated with Lp-PLA2 activity could evaluate whether this relationship is causal. METHODS AND RESULTS: A meta-analysis including a total of 12 studies (5 prospective, 4 case-control, 1 case-only, and 2 cross-sectional studies; n=26 118) was undertaken to examine the association of the following: (1) Lp-PLA2 activity versus cardiovascular biomarkers and risk factors and CHD events (2 prospective studies; n=4884); (2) PLA2G7 single-nucleotide polymorphisms and Lp-PLA2 activity (3 prospective, 2 case-control, 2 cross-sectional studies; up to n=6094); and (3) PLA2G7 single-nucleotide polymorphisms and angiographic coronary artery disease (2 case-control, 1 case-only study; n=4971 cases) and CHD events (5 prospective, 2 case-control studies; n=5523). Lp-PLA2 activity correlated with several CHD risk markers. Hazard ratios for CHD events for the top versus bottom quartile of Lp-PLA2 activity were 1.61 (95% confidence interval, 1.31 to 1.99) and 1.17 (95% confidence interval, 0.91 to 1.51) after adjustment for baseline traits. Of 7 single-nucleotide polymorphisms, rs1051931 (A379V) showed the strongest association with Lp-PLA2 activity, with VV subjects having 7.2% higher activity than AAs. Genotype was not associated with risk markers, angiographic coronary disease (odds ratio, 1.03; 95% confidence interval, 0.80 to 1.32), or CHD events (odds ratio, 0.98; 95% confidence interval, 0.82 to 1.17). CONCLUSIONS: Unlike Lp-PLA2 activity, PLA2G7 variants associated with modest effects on Lp-PLA2 activity were not associated with cardiovascular risk markers, coronary atheroma, or CHD. Larger association studies, identification of single-nucleotide polymorphisms with larger effects, or randomized trials of specific Lp-PLA2 inhibitors are needed to confirm or refute a contributory role for Lp-PLA2 in CHD.
ESTHER : Casas_2010_Circulation_121_2284
PubMedSearch : Casas_2010_Circulation_121_2284
PubMedID: 20479152
Gene_locus related to this paper: human-PLA2G7

Title : The N-terminal region of comparative gene identification-58 (CGI-58) is important for lipid droplet binding and activation of adipose triglyceride lipase - Gruber_2010_J.Biol.Chem_285_12289
Author(s) : Gruber A , Cornaciu I , Lass A , Schweiger M , Poeschl M , Eder C , Kumari M , Schoiswohl G , Wolinski H , Kohlwein SD , Zechner R , Zimmermann R , Oberer M
Ref : Journal of Biological Chemistry , 285 :12289 , 2010
Abstract : In mammals, excess energy is stored in the form of triacylglycerol primarily in lipid droplets of white adipose tissue. The first step of lipolysis (i.e. the mobilization of fat stores) is catalyzed by adipose triglyceride lipase (ATGL). The enzymatic activity of ATGL is strongly enhanced by CGI-58 (comparative gene identification-58), and the loss of either ATGL or CGI-58 function causes systemic triglyceride accumulation in humans and mice. However, the mechanism by which CGI-58 stimulates ATGL activity is unknown. To gain insight into CGI-58 function using structural features of the protein, we generated a three-dimensional homology model based on sequence similarity with other proteins. Interestingly, the model of CGI-58 revealed that the N terminus forms an extension of the otherwise compact structure of the protein. This N-terminal region (amino acids 1-30) harbors a lipophilic tryptophan-rich stretch, which affects the localization of the protein. (1)H NMR experiments revealed strong interaction between the N-terminal peptide and dodecylphosphocholine micelles as a lipid droplet-mimicking system. A role for this N-terminal region of CGI-58 in lipid droplet binding was further strengthened by localization studies in cultured cells. Although wild-type CGI-58 localizes to the lipid droplet, the N-terminally truncated fragments of CGI-58 are dispersed in the cytoplasm. Moreover, CGI-58 lacking the N-terminal extension loses the ability to stimulate ATGL, implying that the ability of CGI-58 to activate ATGL is linked to correct localization. In summary, our study shows that the N-terminal, Trp-rich region of CGI-58 is essential for correct localization and ATGL-activating function of CGI-58.
ESTHER : Gruber_2010_J.Biol.Chem_285_12289
PubMedSearch : Gruber_2010_J.Biol.Chem_285_12289
PubMedID: 20164531