Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets

被引：1306

作者：

Furuhashi, Masato ^{[1
]}

Hotamisligil, Goekhan S. ^{[1
]}

机构：

[1] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA

来源：

NATURE REVIEWS DRUG DISCOVERY | 2008年 / 7卷 / 06期

关键词：

D O I：

10.1038/nrd2589

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Lipids are vital components of many biological processes and crucial in the pathogenesis of numerous common diseases, but the specific mechanisms coupling intracellular lipids to biological targets and signalling pathways are not well understood. This is particularly the case for cells burdened with high lipid storage, trafficking and signalling capacity such as adipocytes and macrophages. Here, we discuss the central role of lipid chaperones-the fatty acid-binding proteins (FABPs)-in lipid-mediated biological processes and systemic metabolic homeostasis through the regulation of diverse lipid signals, and highlight their therapeutic significance. Pharmacological agents that modify FABP function may provide tissue-specific or cell-type-specific control of lipid signalling pathways, inflammatory responses and metabolic regulation, potentially providing a new class of drugs for diseases such as obesity, diabetes and atherosclerosis.

引用

页码：489 / 503

页数：15

共 101 条

[11]

BOHMER FD, 1987, J BIOL CHEM, V262, P15137

[12] Combined adipocyte-macrophage fatty acid-binding protein deficiency improves metabolism, atherosclerosis, and survival in apolipoprotein E-deficient mice [J].

Boord, JB ;

Maeda, K ;

Makowski, L ;

Babaev, VR ;

Fazio, S ;

Linton, MF ;

Hotamisligil, GS .

CIRCULATION, 2004, 110 (11) :1492-1498

[13] Adipocyte fatty acid-binding protein, aP2, alters late atherosclerotic lesion formation in severe hypercholesterolemia [J].

Boord, JB ;

Maeda, K ;

Makowski, L ;

Babaev, VR ;

Fazio, S ;

Linton, MF ;

Hotamisligil, GS .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2002, 22 (10) :1686-1691

[14] Regulation of metabolic responses by adipocyte/macrophage fatty acid-binding proteins in leptin-deficient mice [J].

Cao, Haiming ;

Maeda, Kazuhisa ;

Gorgun, Cem Z. ;

Kim, Hyo-Jeong ;

Park, So-Young ;

Shulman, Gerald I. ;

Kim, Jason K. ;

Hotamisligil, Gokhan S. .

DIABETES, 2006, 55 (07) :1915-1922

[15] The multigene family of fatty acid-binding proteins (FABPs): Function, structure and polymorphism [J].

Chmurzynska, A .

JOURNAL OF APPLIED GENETICS, 2006, 47 (01) :39-48

[16] Deletion of the gene encoding H-FABP/MDGI has no overt effects in the mammary gland [J].

Clark, AJ ;

Neil, C ;

Gusterson, B ;

McWhir, J ;

Binas, B .

TRANSGENIC RESEARCH, 2000, 9 (06) :439-444

[17]

Coe NR, 1999, J LIPID RES, V40, P967

[18] Physiological properties and functions of intracellular fatty acid-binding proteins [J].

Coe, NR ;

Bernlohr, DA .

BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM, 1998, 1391 (03) :287-306

[19] Fatty acid binding proteins reduce 15-lipoxygenase-inducedoxygenation of linoleic acid and arachidonic acid [J].

Ek, BA ;

Cistola, DP ;

Hamilton, JA ;

Kaduce, TL ;

Spector, AA .

BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM, 1997, 1346 (01) :75-85

[20] Invertebrate intracellular fatty acid binding proteins [J].

Esteves, A ;

Ehrlich, R .

COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY, 2006, 142 (3-4) :262-274

← 1 2 3 4 5 6 7 8 9 10 →