Identification of a Lipokine, a Lipid Hormone Linking Adipose Tissue to Systemic Metabolism

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2008 Sep 23

PMID 18805087

Citations 524

Authors

Haiming Cao

Kristin Gerhold

Jared R Mayers

Michelle M Wiest

Steven M Watkins

Gokhan S Hotamisligil

Affiliations

Soon will be listed here.

Abstract

Dysregulation of lipid metabolism in individual tissues leads to systemic disruption of insulin action and glucose metabolism. Utilizing quantitative lipidomic analyses and mice deficient in adipose tissue lipid chaperones aP2 and mal1, we explored how metabolic alterations in adipose tissue are linked to whole-body metabolism through lipid signals. A robust increase in de novo lipogenesis rendered the adipose tissue of these mice resistant to the deleterious effects of dietary lipid exposure. Systemic lipid profiling also led to identification of C16:1n7-palmitoleate as an adipose tissue-derived lipid hormone that strongly stimulates muscle insulin action and suppresses hepatosteatosis. Our data reveal a lipid-mediated endocrine network and demonstrate that adipose tissue uses lipokines such as C16:1n7-palmitoleate to communicate with distant organs and regulate systemic metabolic homeostasis.

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References

Furuhashi M, Hotamisligil G . Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov. 2008; 7(6):489-503. PMC: 2821027. DOI: 10.1038/nrd2589. View

Furuhashi M, Tuncman G, Gorgun C, Makowski L, Atsumi G, Vaillancourt E . Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature. 2007; 447(7147):959-65. PMC: 4076119. DOI: 10.1038/nature05844. View

Paillard F, Catheline D, Le Duff F, Bouriel M, Deugnier Y, Pouchard M . Plasma palmitoleic acid, a product of stearoyl-coA desaturase activity, is an independent marker of triglyceridemia and abdominal adiposity. Nutr Metab Cardiovasc Dis. 2007; 18(6):436-40. DOI: 10.1016/j.numecd.2007.02.017. View

Moraes R, Blondet A, Birkenkamp-Demtroeder K, Tirard J, Orntoft T, Gertler A . Study of the alteration of gene expression in adipose tissue of diet-induced obese mice by microarray and reverse transcription-polymerase chain reaction analyses. Endocrinology. 2003; 144(11):4773-82. DOI: 10.1210/en.2003-0456. View

Ntambi J, Miyazaki M . Regulation of stearoyl-CoA desaturases and role in metabolism. Prog Lipid Res. 2003; 43(2):91-104. DOI: 10.1016/s0163-7827(03)00039-0. View

Kim J, Fillmore J, Sunshine M, Albrecht B, Higashimori T, Kim D . PKC-theta knockout mice are protected from fat-induced insulin resistance. J Clin Invest. 2004; 114(6):823-7. PMC: 516267. DOI: 10.1172/JCI22230. View

Hotamisligil G, Johnson R, Distel R, Ellis R, Papaioannou V, Spiegelman B . Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science. 1996; 274(5291):1377-9. DOI: 10.1126/science.274.5291.1377. View

Stein D, Stevenson B, Chester M, Basit M, DANIELS M, Turley S . The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation. J Clin Invest. 1997; 100(2):398-403. PMC: 508203. DOI: 10.1172/JCI119546. View

Waters K, Miller C, Ntambi J . Localization of a polyunsaturated fatty acid response region in stearoyl-CoA desaturase gene 1. Biochim Biophys Acta. 1998; 1349(1):33-42. DOI: 10.1016/s0005-2760(97)00069-6. View

10.

Ntambi J . Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol. J Lipid Res. 1999; 40(9):1549-58. View

11.

Folch J, Lees M, SLOANE STANLEY G . A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957; 226(1):497-509. View

12.

Todaro G, Green H . Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J Cell Biol. 1963; 17:299-313. PMC: 2106200. DOI: 10.1083/jcb.17.2.299. View

13.

Hiraoka-Yamamoto J, Ikeda K, Negishi H, Mori M, Hirose A, Sawada S . Serum lipid effects of a monounsaturated (palmitoleic) fatty acid-rich diet based on macadamia nuts in healthy, young Japanese women. Clin Exp Pharmacol Physiol. 2005; 31 Suppl 2:S37-8. DOI: 10.1111/j.1440-1681.2004.04121.x. View

14.

Eckel R, Grundy S, Zimmet P . The metabolic syndrome. Lancet. 2005; 365(9468):1415-28. DOI: 10.1016/S0140-6736(05)66378-7. View

15.

Kuriyama H, Liang G, Engelking L, Horton J, Goldstein J, Brown M . Compensatory increase in fatty acid synthesis in adipose tissue of mice with conditional deficiency of SCAP in liver. Cell Metab. 2005; 1(1):41-51. DOI: 10.1016/j.cmet.2004.11.004. View

16.

Maeda K, Cao H, Kono K, Gorgun C, Furuhashi M, Uysal K . Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes. Cell Metab. 2005; 1(2):107-19. DOI: 10.1016/j.cmet.2004.12.008. View

17.

Warensjo E, Riserus U, Vessby B . Fatty acid composition of serum lipids predicts the development of the metabolic syndrome in men. Diabetologia. 2005; 48(10):1999-2005. DOI: 10.1007/s00125-005-1897-x. View

18.

Ginsberg H, Zhang Y, Hernandez-Ono A . Metabolic syndrome: focus on dyslipidemia. Obesity (Silver Spring). 2006; 14 Suppl 1:41S-49S. DOI: 10.1038/oby.2006.281. View

19.

Tuncman G, Erbay E, Hom X, De Vivo I, Campos H, Rimm E . A genetic variant at the fatty acid-binding protein aP2 locus reduces the risk for hypertriglyceridemia, type 2 diabetes, and cardiovascular disease. Proc Natl Acad Sci U S A. 2006; 103(18):6970-5. PMC: 1447594. DOI: 10.1073/pnas.0602178103. View

20.

Avramoglu R, Basciano H, Adeli K . Lipid and lipoprotein dysregulation in insulin resistant states. Clin Chim Acta. 2006; 368(1-2):1-19. DOI: 10.1016/j.cca.2005.12.026. View