Tài liệu Báo cáo khoa học: Angiopoietin-like proteins: emerging targets for treatment of obesity and

MINIREVIEW

Angiopoietin-like proteins: emerging targets for treatment

of obesity and related metabolic diseases

Tsuyoshi Kadomatsu, Mitsuhisa Tabata and Yuichi Oike

Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Japan

Introduction

A worldwide increase in obesity due to lifestyle

changes, such as inactivity and overnutrition, is an

increasing medical and social problem in developed

and developing countries [1]. Obesity increases the risk

of related metabolic diseases, including type 2 diabetes,

hypertension, hyperlipidemia and cardiovascular dis￾ease [2], which interfere with healthy aging. A major

metabolic manifestation of obesity in the early phase is

systemic insulin resistance [3]. Recently, the concept

has emerged that persistent low-grade activation of

proinflammatory pathways in obese adipose tissue

directly promotes systemic insulin resistance [1,4,5],

suggesting that identification of the molecular mecha￾nisms underlying adipose tissue inflammation could

provide clues for the development of effective preven￾tive and therapeutic approaches to obesity-related insu￾lin resistance.

We and others independently identified seven

angiopoietin-like proteins (ANGPTLs) [6]. ANGPTLs

are structurally similar to angiopoietins, which are

Keywords

adipose tissue; ANGPTL2; ANGPTL6 ⁄ AGF;

cardiovascular disease; chronic

inflammation; energy metabolism;

insulin resistance; metabolic syndrome;

obesity; obesity-related metabolic disease

Correspondence

Y. Oike, Department of Molecular Genetics,

Graduate School of Medical Sciences,

Kumamoto University, 1-1-1 Honjo,

Kumamoto 860-8556, Japan

Fax: +81 96 373 5145

Tel: +81 96 373 5140

E-mail: [email protected]

Note

Tsuyoshi Kadomatsu and Mitsuhisa Tabata

contributed equally to this work

(Received 21 July 2010, revised 21

November 2010, accepted 29 November

2010)

doi:10.1111/j.1742-4658.2010.07979.x

Obesity and related metabolic diseases, such as type 2 diabetes, hyperten￾sion and hyperlipidemia are an increasingly prevalent medical and social

problem in developed and developing countries. These conditions are asso￾ciated with increased risk of cardiovascular disease, the leading cause of

death. Therefore, it is important to understand the molecular basis underly￾ing obesity and related metabolic diseases in order to develop effective pre￾ventive and therapeutic approaches against these conditions. Recently, a

family of proteins structurally similar to the angiogenic-regulating factors

known as angiopoietins was identified and designated ‘angiopoietin-like

proteins’ (ANGPTLs). Encoded by seven genes, ANGPTL1–7 all possess

an N-terminal coiled-coil domain and a C-terminal fibrinogen-like domain,

both characteristic of angiopoietins. ANGPTLs do not bind to either the

angiopoietin receptor Tie2 or the related protein Tie1, indicating that these

ligands function differently from angiopoietins. Like angiopoietins, some

ANGPTLs potently regulate angiogenesis, but ANGPTL3, -4 and ANG￾PTL6 ⁄ angiopoietin-related growth factor (AGF) directly regulate lipid,

glucose and energy metabolism independent of angiogenic effects. Recently,

we found that ANGPTL2 is a key adipocyte-derived inflammatory media￾tor that links obesity to systemic insulin resistance. In this minireview, we

focus on the roles of ANGPTL2 and ANGPTL6 ⁄AGF in obesity and

related metabolic diseases, and discuss the possibility that both could func￾tion as molecular targets for the prevention and treatment of obesity and

metabolic diseases.

Abbreviations

AGF, angiopoietin-related growth factor; ANGPTL, angiopoietin-like protein; PGC-1a, peroxisome proliferator-activated receptor-c (PPARc)

coactivator 1a; PPAR, peroxisome proliferator-activated receptor.

FEBS Journal 278 (2011) 559–564 ª 2010 The Authors Journal compilation ª 2010 FEBS 559