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Fax Number:

(310) 794-5446

Work Phone Number:

(310) 267-2752
(310) 794-5631

Laboratory Address:

Laboratory
Department of Human Genetics
Gonda Building, 6th floor
UCLA
Los Angeles, CA 90095
UNITED STATES

Mailing Address:

Mailing Address
Department of Human Genetics
David Geffen School of Medicine at UCLA
695 Charles E. Young Drive South
Los Angeles, CA 90095
UNITED STATES

Office Address:

Office
Department of Human Genetics
Gonda Building, 6th floor
Los Angeles, CA 90095
UNITED STATES

Email Address:

reuek@ucla.edu

Detailed Biography:

Research Interest:

Genes underlying disorders in lipid and glucose metabolism

We are interested in identifying genes that underlie abnormalities in lipid and glucose metabolism using the mouse as a model. Much of our recent work has focused on the fatty liver dystrophy (fld) mutation, which results in lipodystrophy (lack of fat tissue), insulin resistance, and increased susceptibility to atherosclerosis. Using a positional cloning approach, we identified the fld mutation in a novel gene that we named Lipin. We are studying the role of lipin in fat tissue development and metabolic disorders in several models, including engineered mouse strains, cultured cells, human adipose tissue, and invertebrate organisms. A second positional cloning project that is underway is aimed at isolating a gene mutation that confers resistance to hypercholesterolemia and atherosclerosis. We are also pleased to be a member of the BayGenomics consortium that is performing analysis of gene function in the mouse on a large scale using gene-trap technology.

Péterfy M, Harris TE, Fujita N, Reue K Insulin-stimulated interaction with 14-3-3 promotes cytoplasmic localization of lipin-1 in adipocytes. J Biol Chem 2010; Epub ahead of print Dec 2, 2009: .

Donkor J, Zhang P, Wong S, O?Loughlin L, Kok B, Dewald J, Brindley DN, Reue K A conserved serine residue is required for the phosphatidate phosphatase activity but not coactivator functions of lipin-1 and lipin-2. J Biol Chem 2009; 284: 29968-29978.

Phan J, Hickey M, Zhang P, Chesselet M, Reue K Adipose tissue dysfunction tracks disease progression in two Huntington?s disease mouse models. Hum Mol Genet 2009; 18: 1006-1016.

Takeuchi K, Reue K Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis. Am J Physiol Endocrinol Metab 2009; 296: E1195-209.

Hegele RA, Reue K Hoofbeats, zebras, and insights into insulin resistance. J Clin Invest 2009; 119: 249-251.

Chao LC, Wroblewski K, Zhang A, Pei L, Vergnes L, Ilkayeva OR, Ding S, Reue K, Watt MJ, Newgard CB, Pilch PF, Hevener AL, Tontonoz P Insulin resistance and altered systemic glucose metabolism in mice lacking Nur77. Diabetes 2009; 58: 2788-2796.

Reue K, Dwyer J Lipin proteins and metabolic homeostasis. J Lipid Res 2009; 50: Suppl: S109-114.

Brindley DN, Pilquil C, Sariahmetoglu M, Reue K Phosphatidate degradation: Phosphatidate phosphatases (lipins) and lipid phosphate phosphatases. Biochim Biophys Acta 2009; 1791: 956-961.

Dean JT, Tran L, Beaven S, Tontonoz P, Reue K, Dipple KM, Liao JC Resistance to diet-induced obesity in mice with synthetic glyoxylate shunt. Cell Metab 2009; 9: 525-536.

Bou Khalil M, Sundaram M, Zhang HY, Links PH, Raven JF, Manmontri B, Sariahmetoglu M, Tran K, Reue K, Brindley DN, Yao Z The level and compartmentalization of phosphatidate phosphatase-1 (lipin-1) control the assembly and secretion of hepatic very low density lipoproteins. J Lipid Res 2009; 50: 47-58.

Reue K The lipin protein family: mutations and metabolism. Curr Opin Lipidol 2009; 20: 165-170.

Donkor J, Sparks LM, Xie H, Smith SR, Reue K Adipose tissue lipin-1 expression is correlated with PPAR? gene expression and insulin sensitivity in healthy young men. J Clin Endocrinol Metab 2008; 93: 233-239.

Manmontri B, Sariahmetoglu M, Donkor J, Bou Khalil M, Yao Z, Reue K, Lehner R, Brindley DN Glucocorticoids and cAMP selectively increase hepatic lipin-1 expression and insulin acts antagonistically. J Lipid Res 2008; 49: 1056-1067.

Nagle CA, Vergnes L, Dejong H, Wang S, Lewin TM, Reue K, Coleman RA Identification of a novel sn-glycerol-3-phosphate acyltransferase isoform, GPAT4, as the enzyme deficient in Agpat6?/? mice. J Lipid Res 2008; 49: 823-831.

Lusis AJ, Attie AD, Reue K Metabolic Syndrome: from epidemiology to gene networks. Nat Rev Genet 2008; 9: 819-830.

Reue K, Brindley DN Multiple roles for lipins/phosphatidate phosphatase enzymes in lipid metabolism. J Lipid Res 2008; 49: 2493-2503.

Zhang P, O?Loughlin L, Brindley, DN, Reue K Regulation of lipin-1 gene expression by glucocorticoids during adipogenesis. J Lipid Res 2008; 49: 1519-1528.

Reue K, Zhang P The lipin protein family: dual roles in lipid biosynthesis and gene expression. FEBS Lett 2008; 582: 90-96.

Ji J, Lee RT, Vergnes L, Fong LG, Stewart CL, Reue K, Young SG, Zhang Q, Shanahan CM, Lammerding J Cell nuclei spin in the absence of lamin B1. J Biol Chem 2007; 282: 20015-20026.

Reue K, Donkor J Genetic factors in type 2 diabetes: all in the (lipin) family. Diabetes 2007; 56: 2842-2843.

Péterfy M, Ben-Zeev O, Mao HZ, Weissglas-Volkov D. Aouizerat BE, Pullinger CR, Frost PH, Kane JP, Malloy MJ, Reue K, Pajukanta P, Doolittle MH Mutations in LMF1 cause combined lipase deficiency and severe hypertriglyceridemia. Nat Genet 2007; 39: 1483-1487.

Donkor J, Sariahmetoglu M, Dewald J, Brindley DN, Reue K Three mammalian lipins act as phosphatidate phosphatases with distinct tissue expression patterns. J Biol Chem 2007; 282: 3450-3457.

Lindegaard, B., Larsen, L.F., Hansen, A.-B.E., Gerstoft, J., Pedersen, B.K., Reue, K Adipose tissue lipin expression levels distinguish HIV patients with and without lipodystrophy. Int. J. Obes 2006; 31: 449-456.

Vergnes L Beigneux AP Davis R Watkins SM Young SG Reue K Agpat6 deficiency causes subdermal lipodystrophy and resistance to obesity. J Lipid Res 2006; 47: 745-754.

Beigneux AP Vernes L Qiao X Quatela S Davis R Watkins SM Coleman RA Walzem RL Philips M Reue K Young, SG Agpat6--a novel lipid biosynthetic gene required for triacylglycerol production in mammary epithelium. J Lipid Res 2006; 47: 734-744.

Suviolahti E Reue K Cantor RM Phan J Gentile M Naukkarinen J Soro-Paavonen A Oksanen L Kaprio J Rissanen A Salomaa V Kontula K Taskinen MR Pajukanta P Peltonen L. Cross-species analyses implicate Lipin 1 involvement in human glucose metabolism. Hum Mol Genet 2006; 15: 377-386.

Lammerding J Fong L Ji JY Reue K Stewart CL Young SG Lee RT Lamins A and C but not lamin B1 regulate nuclear mechanics. J. Biol. Chem. 2006; 281: 25768-25780.

Xu J Lee WN Phan J Saad MF Reue K Kurland IJ Lipin deficiency impairs diurnal metabolic fuel switching. Diabetes 2006; 55: 3429-3438.

Yao-Borengasser A Rasouli N Varma V Miles LM Phanavanh B Starks TN Phan J Spencer HJ 3rd McGehee RE Jr Reue K Kern PA Lipin expression is attenuated in adipose tissue of insulin-resistant human subjects and increases with peroxisome proliferator-activated receptor gamma activation. Diabetes 2006; 55: 2811-2818.

Reue K Phan J Metabolic consequences of lipodystrophy in mouse models. Curr. Opin. Clin. Nutr. Metab. Care 2006; 9: 436-441.

Reue K, Vergnes L Systems biology approaches to metabolic and cardiovascular disorders. Approaches to lipid metabolism gene identification and characterization in the post-genomic era. J Lipid Res 2006; 47: 1891-1907.

Peterfy, M. Phan, J. Reue, K. Alternatively spliced lipin isoforms exhibit distinct expression pattern, subcellular localization and role in adipogenesis. J. Biol. Chem. 2005; 280: 32883-32889.

Phan, J Peterfy, M Reue, K Biphasic expression of lipin suggests dual roles in adipocyte development.. Drug news & perspectives. . 2005; 18(1): 5-11.

Vergnes, L., Peterfy, M., Bergo, M., Young, S.G., Reue, K. Lamin B1 is required for mouse development and nuclear integrity. Proc. Natl. Acad. Sci. USA 2004; 101: 10428-10433.

Phan, J., Peterfy, M., Reue, K. Lipin expression preceding PPAR-gamma is critical for adipogenesis in vivo and in vitro. J. Biol. Chem. 2004; 279: 29558-29564.

Peterfy, M., Phan, J., Xu, P., Reue, K. Lipodystrophy in the fld mouse results from mutation in a novel nuclear protein, lipin.. Nature Genetics 2001; 27: 121-124.

Mouzeyan, A., Choi, J., Allayee, H., Sinsheimer, J., Phan, J., Castellani, L.W., Reue, K., Lusis, A.J., Davis, R.C. A gene conferring resistance to diet-induced hypercholesterolemia and atherosclerosis on mouse chromosome 2.. J. Lipid Res. 2000; 41: 573-582.

Harte, R.A., Hulten, L.M., Lindmark, H., Reue, K., Schotz, M.C., Khoo, J., Rosenfeld, M.E. Low level expression of hormone-sensitive lipase in arterial macrophage-derived foam cells: potential explanation for low rates of cholesteryl ester hydrolysis.. Atherosclerosis 2000; 149: 343-350.

Phan, J., Reue, K., Peterfy, M. MS-IRS: PCR: A simple method for the isolation of microsatellites.. BioTechniques 2000; 28: 18-20.

Reue, K., Peterfy, M. Mouse models of lipodystrophy.. Curr. Atherosclerosis Reports 2000; 2: 390-396.

Phan, J Reue, K Lipin, a lipodystrophy and obesity gene.. Cell metabolism. . 2005; 1(1): 73-83.

Fong, LG Ng, JK Meta, M Coté, N Yang, SH Stewart, CL Sullivan, T Burghardt, A Majumdar, S Reue, K Bergo, MO Young, SG Heterozygosity for Lmna deficiency eliminates the progeria-like phenotypes in Zmpste24-deficient mice.. Proceedings of the National Academy of Sciences of the United States of America. . 2004; 101(52): 18111-6.

Vergnes, L Phan, J Strauss, M Tafuri, S Reue, K Cholesterol and cholate components of an atherogenic diet induce distinct stages of hepatic inflammatory gene expression.. The Journal of biological chemistry. . 2003; 278(44): 42774-84.

Vergnes, L Phan, J Stolz, A Reue, K A cluster of eight hydroxysteroid dehydrogenase genes belonging to the aldo-keto reductase supergene family on mouse chromosome 13.. Journal of lipid research. . 2003; 44(3): 503-11.

Phan, J Pesaran, T Davis, RC Reue, K The Diet1 locus confers protection against hypercholesterolemia through enhanced bile acid metabolism.. The Journal of biological chemistry.. 2002; 277(1): 469-77.

Reue, K Glueck, SB Accumulating evidence for differences during preadipocyte development: Focus on "Differential gene expression in white and brown preadipocytes".. Physiological genomics. . 2001; 7(1): 1-2.

Kast, HR Nguyen, CM Sinal, CJ Jones, SA Laffitte, BA Reue, K Gonzalez, FJ Willson, TM Edwards, PA Farnesoid X-activated receptor induces apolipoprotein C-II transcription: a molecular mechanism linking plasma triglyceride levels to bile acids.. Molecular endocrinology (Baltimore, Md.) . 2001; 15(10): 1720-8.

Karlsson, M Reue, K Xia, YR Lusis, AJ Langin, D Tornqvist, H Holm, C Exon-intron organization and chromosomal localization of the mouse monoglyceride lipase gene.. Gene. . 2001; 272(1-2): 11-8.

Reue, K Xu, P Wang, XP Slavin, BG Adipose tissue deficiency, glucose intolerance, and increased atherosclerosis result from mutation in the mouse fatty liver dystrophy (fld) gene.. Journal of lipid research. . 2000; 41(7): 1067-76.

Klingenspor, M Xu, P Cohen, RD Welch, C Reue, K Altered gene expression pattern in the fatty liver dystrophy mouse reveals impaired insulin-mediated cytoskeleton dynamics.. The Journal of biological chemistry. . 1999; 274(33): 23078-84.

Escary, JL Choy, HA Reue, K Wang, XP Castellani, LW Glass, CK Lusis, AJ Schotz, MC Paradoxical effect on atherosclerosis of hormone-sensitive lipase overexpression in macrophages.. Journal of lipid research. . 1999; 40(3): 397-404.

Oswell, GM Doolittle, MH Reue, K Preparation of YAC end fragments from the whitehead/MIT mouse YAC library pRML vectors.. BioTechniques. . 1999; 26(3): 396-8, 400, 402.

Rehnmark, S Giometti, CS Slavin, BG Doolittle, MH Reue, K The fatty liver dystrophy mutant mouse: microvesicular steatosis associated with altered expression levels of peroxisome proliferator-regulated proteins.. Journal of lipid research. . 1998; 39(11): 2209-17.

Reue, K mRNA quantitation techniques: considerations for experimental design and application.. The Journal of nutrition. . 1998; 128(11): 2038-44.

Escary, JL Choy, HA Reue, K Schotz, MC Hormone-sensitive lipase overexpression increases cholesteryl ester hydrolysis in macrophage foam cells.. Arteriosclerosis, thrombosis, and vascular biology. . 1998; 18(6): 991-8.