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Project 1: Lipin proteins—masters of fat synthesis

How lipid droplets "TAG" along: Glycerolipid synthetic enzymes and lipid storage. Wang H, Airola MV, Reue K. Biochim Biophys Acta. 2017 Jun 19. pii: S1388-1981(17)30114-2. doi: 10.1016/j.bbalip.2017.06.010. Review. Lipin proteins and glycerolipid metabolism: Roles at the ER membrane and beyond. Zhang P, Reue K. Biochim Biophys Acta. 2017 Apr 11. pii: S0005-2736(17)30123-2. doi: 10.1016/j.bbamem.2017.04.007. Review. Lipin-1 and lipin-3 together determine adiposity in vivo. Csaki LS, Dwyer JR, Li X, Nguyen MH, Dewald J, Brindley DN, Lusis AJ, Yoshinaga Y, de Jong P, Fong L, Young SG, Reue K. Mol Metab. 2013 Nov 28;3(2):145-54. doi: 10.1016/j.molmet.2013.11.008. eCollection 2014 Apr. Lipins, lipinopathies, and the modulation of cellular lipid storage and signaling. Csaki LS, Dwyer JR, Fong LG, Tontonoz P, Young SG, Reue K. Prog Lipid Res. 2013 Jul;52(3):305-16. doi: 10.1016/j.plipres.2013.04.001. Review. Mouse lipin-1 and lipin-2 cooperate to maintain glycerolipid homeostasis in liver and aging cerebellum. Dwyer JR, Donkor J, Zhang P, Csaki LS, Vergnes L, Lee JM, Dewald J, Brindley DN, Atti E, Tetradis S, Yoshinaga Y, De Jong PJ, Fong LG, Young SG, Reue K. Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):E2486-95. doi: 10.1073/pnas.1205221109. Lipin-1 phosphatidic phosphatase activity modulates phosphatidate levels to promote peroxisome proliferator-activated receptor γ (PPARγ) gene expression during adipogenesis. Zhang P, Takeuchi K, Csaki LS, Reue K. J Biol Chem. 2012 Jan 27;287(5):3485-94. doi: 10.1074/jbc.M111.296681. A thematic review series: lipid droplet storage and metabolism: from yeast to man. Reue K. J Lipid Res. 2011 Nov;52(11):1865-8. doi: 10.1194/jlr.E020602. Review. Lipins: multifunctional lipid metabolism proteins. Csaki LS, Reue K. Annu Rev Nutr. 2010 Aug 21;30:257-72. doi: 10.1146/annurev.nutr.012809.104729. Review. Insulin-stimulated interaction with 14-3-3 promotes cytoplasmic localization of lipin-1 in adipocytes. Péterfy M, Harris TE, Fujita N, Reue K. J Biol Chem. 2010 Feb 5;285(6):3857-64. doi: 10.1074/jbc.M109.072488. A conserved serine residue is required for the phosphatidate phosphatase activity but not the transcriptional coactivator functions of lipin-1 and lipin-2. Donkor J, Zhang P, Wong S, O'Loughlin L, Dewald J, Kok BP, Brindley DN, Reue K. J Biol Chem. 2009 Oct 23;284(43):29968-78. doi: 10.1074/jbc.M109.023663. The lipin family: mutations and metabolism. Reue K. Curr Opin Lipidol. 2009 Jun;20(3):165-70. doi: 10.1097/MOL.0b013e32832adee5. Review. Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis. Takeuchi K, Reue K. Am J Physiol Endocrinol Metab. 2009 Jun;296(6):E1195-209. doi: 10.1152/ajpendo.90958.2008. Review. Phosphatidate degradation: phosphatidate phosphatases (lipins) and lipid phosphate phosphatases. Brindley DN, Pilquil C, Sariahmetoglu M, Reue K. Biochim Biophys Acta. 2009 Sep;1791(9):956-61. doi: 10.1016/j.bbalip.2009.02.007. Review. Lipin proteins and metabolic homeostasis. Reue K, Dwyer JR. J Lipid Res. 2009 Apr;50 Suppl:S109-14. doi: 10.1194/jlr.R800052-JLR200. Review. Regulation of lipin-1 gene expression by glucocorticoids during adipogenesis. Zhang P, O'Loughlin L, Brindley DN, Reue K. J Lipid Res. 2008 Jul;49(7):1519-28. doi: 10.1194/jlr.M800061-JLR200. The role of lipin 1 in adipogenesis and lipid metabolism. Reue K. Novartis Found Symp. 2007;286:58-68; discussion 68-71, 162-3, 196-203. Review. Genetic factors in type 2 diabetes: all in the (lipin) family. Reue K, Donkor J. Diabetes. 2007 Dec;56(12):2842-3. Review. The lipin protein family: dual roles in lipid biosynthesis and gene expression. Reue K, Zhang P. FEBS Lett. 2008 Jan 9;582(1):90-6. Review. Adipose tissue lipin-1 expression is correlated with peroxisome proliferator-activated receptor alpha gene expression and insulin sensitivity in healthy young men. Donkor J, Sparks LM, Xie H, Smith SR, Reue K. J Clin Endocrinol Metab. 2008 Jan;93(1):233-9. Three mammalian lipins act as phosphatidate phosphatases with distinct tissue expression patterns. Donkor J, Sariahmetoglu M, Dewald J, Brindley DN, Reue K. J Biol Chem. 2007 Feb 9;282(6):3450-7. Adipose tissue lipin expression levels distinguish HIV patients with and without lipodystrophy. Lindegaard B, Larsen LF, Hansen AB, Gerstoft J, Pedersen BK, Reue K Int J Obes (Lond). 2007 Mar;31(3):449-56. Lipin, a lipodystrophy and obesity gene. Phan J, Reue K. Cell Metab. 2005 Jan;1(1):73-83. Alternatively spliced lipin isoforms exhibit distinct expression pattern, subcellular localization, and role in adipogenesis. Péterfy M, Phan J, Reue K. J Biol Chem. 2005 Sep 23;280(38):32883-9. Biphasic expression of lipin suggests dual roles in adipocyte development. Phan J, Peterfy M, Reue K. Drug News Perspect. 2005 Jan-Feb;18(1):5-11. Review. Lipin expression preceding peroxisome proliferator-activated receptor-gamma is critical for adipogenesis in vivo and in vitro. Phan J, Péterfy M, Reue K. J Biol Chem. 2004 Jul 9;279(28):29558-64. Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin. Péterfy M, Phan J, Xu P, Reue K. Nat Genet. 2001 Jan;27(1):121-4.

Project 2: Diet1 and resistance to high cholesterol levels and cardiovascular disease

Diet1 is a regulator of fibroblast growth factor 15/19-dependent bile acid synthesis. Reue K, Lee JM, Vergnes L. Dig Dis. 2015;33(3):307-13. doi: 10.1159/000371649. Regulation of bile acid homeostasis by the intestinal Diet1-FGF15/19 axis. Reue K, Lee JM, Vergnes L. Curr Opin Lipidol. 2014 Apr;25(2):140-7. doi: 10.1097/MOL.0000000000000060. Review. Diet1 functions in the FGF15/19 enterohepatic signaling axis to modulate bile acid and lipid levels. Vergnes L, Lee JM, Chin RG, Auwerx J, Reue K. Cell Metab. 2013 Jun 4;17(6):916-28. doi: 10.1016/j.cmet.2013.04.007. Cholesterol and cholate components of an atherogenic diet induce distinct stages of hepatic inflammatory gene expression. Vergnes L, Phan J, Strauss M, Tafuri S, Reue K. J Biol Chem. 2003 Oct 31;278(44):42774-84. The Diet1 locus confers protection against hypercholesterolemia through enhanced bile acid metabolism. Phan J, Pesaran T, Davis RC, Reue K. J Biol Chem. 2002 Jan 4;277(1):469-77.

Project 3: Pharmacogenomics of statin drugs

Lipin-1 flexes its muscle in autophagy. Zhang P, Reue K. Cell Cycle. 2014;13(24):3789-90. doi: 10.4161/15384101.2014.988105. Lipin-1 regulates autophagy clearance and intersects with statin drug effects in skeletal muscle. Zhang P, Verity MA, Reue K. Cell Metab. 2014 Aug 5;20(2):267-79. doi: 10.1016/j.cmet.2014.05.003.

Project 4: Sex differences in obesity

The Genetic Basis for Sex Differences in Obesity and Lipid Metabolism. Link JC, Reue K. Annu Rev Nutr. 2017 Jun 19. doi: 10.1146/annurev-nutr-071816-064827. Review. A Guide for the Design of Pre-clinical Studies on Sex Differences in Metabolism. Mauvais-Jarvis F, Arnold AP, Reue K. Cell Metab. 2017 Jun 6;25(6):1216-1230. doi: 10.1016/j.cmet.2017.04.033. Review. Sex differences in obesity: X chromosome dosage as a risk factor for increased food intake, adiposity and co-morbidities. Reue K. Physiol Behav. 2017 Mar 8. pii: S0031-9384(17)30005-7. doi: 10.1016/j.physbeh.2017.02.040. Review. Diet, gonadal sex, and sex chromosome complement influence white adipose tissue miRNA expression. Link JC, Hasin-Brumshtein Y, Cantor RM, Chen X, Arnold AP, Lusis AJ, Reue K. BMC Genomics. 2017 Jan 17;18(1):89. doi: 10.1186/s12864-017-3484-1. Increased high-density lipoprotein cholesterol levels in mice with XX versus XY sex chromosomes. Link JC, Chen X, Prien C, Borja MS, Hammerson B, Oda MN, Arnold AP, Reue K. Arterioscler Thromb Vasc Biol. 2015 Aug;35(8):1778-86. doi: 10.1161/ATVBAHA.115.305460. Metabolic impact of sex chromosomes. Link JC, Chen X, Arnold AP, Reue K. Adipocyte. 2013 Apr 1;2(2):74-9. doi: 10.4161/adip.23320. Review. Cell-autonomous sex determination outside of the gonad. Arnold AP, Chen X, Link JC, Itoh Y, Reue K. Dev Dyn. 2013 Apr;242(4):371-9. doi: 10.1002/dvdy.23936. Review. The number of X chromosomes causes sex differences in adiposity in mice. Chen X, McClusky R, Chen J, Beaven SW, Tontonoz P, Arnold AP, Reue K. PLoS Genet. 2012;8(5):e1002709. doi: 10.1371/journal.pgen.1002709.

Project 5: Brown adipose tissue and energy metabolism

Adipocyte browning and higher mitochondrial function in peri-adrenal but not subcutaneous fat in pheochromocytoma. Vergnes L, Davies GR, Lin JY, Yeh MW, Livhits MJ, Harari A, Symonds ME, Sacks HS, Reue K. J Clin Endocrinol Metab. 2016 Nov;101(11):4440-4448. Zbtb16 has a role in brown adipocyte bioenergetics. Plaisier CL, Bennett BJ, He A, Guan B, Lusis AJ, Reue K, Vergnes L. Nutr Diabetes. 2012 Sep 17;2:e46. doi: 10.1038/nutd.2012.21. Heart-type fatty acid-binding protein is essential for efficient brown adipose tissue fatty acid oxidation and cold tolerance. Vergnes L, Chin R, Young SG, Reue K. J Biol Chem. 2011 Jan 7;286(1):380-90. doi: 10.1074/jbc.M110.184754.

Laboratory of Karen Reue | Human Genetics | David Geffen School of Medicine | UCLA