Deficiency of a Lipid Droplet Protein, Perilipin 5, Suppresses Myocardial Lipid Accumulation, Thereby Preventing Type 1 Diabetes-Induced Heart Malfunction

被引：46

作者：

Kuramoto, Kenta ^{[1
]}

Sakai, Fumie ^{[1
]}

Yoshinori, Nana ^{[1
]}

Nakamura, Tomoe Y. ^{[2
]}

Wakabayashi, Shigeo ^{[2
]}

Kojidani, Tomoko ^{[3
,4
]}

Haraguchi, Tokuko ^{[4
,5
,6
]}

Hirose, Fumiko ^{[1
]}

Osumi, Takashi ^{[1
]}

机构：

[1] Univ Hyogo, Grad Sch Life Sci, Kamigori, Hyogo, Japan

[2] Natl Cerebral & Cardiovasc Ctr, Res Inst, Dept Mol Physiol, Suita, Osaka, Japan

[3] Japan Womens Univ, Dept Chem & Biol Sci, Bunkyo Ku, Tokyo 112, Japan

[4] Natl Inst Informat & Commun Technol, Adv ICT Res Inst Kobe, Nishi Ku, Kobe, Hyogo, Japan

[5] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka, Japan

[6] Osaka Univ, Grad Sch Sci, Toyonaka, Osaka 560, Japan

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2014年 / 34卷 / 14期

基金：

日本学术振兴会;

关键词：

FATTY-ACID OXIDATION; KINASE-C ACTIVATION; NADPH OXIDASE; PPAR-ALPHA; LIPOTOXIC CARDIOMYOPATHY; CARDIAC DYSFUNCTION; MOUSE MODEL; PAT-FAMILY; OVEREXPRESSION; RATS;

D O I：

10.1128/MCB.00133-14

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Lipid droplet (LD) is a ubiquitous organelle that stores triacylglycerol and other neutral lipids. Perilipin 5 (Plin5), a member of the perilipin protein family that is abundantly expressed in the heart, is essential to protect LDs from attack by lipases, including adipose triglyceride lipase. Plin5 controls heart metabolism and performance by maintaining LDs under physiological conditions. Aberrant lipid accumulation in the heart leads to organ malfunction, or cardiomyopathy. To elucidate the role of Plin5 in a metabolically disordered state and the mechanism of lipid-induced cardiomyopathy, we studied the effects of streptozotocin-induced type 1 diabetes in Plin5-knockout (KO) mice. In contrast to diabetic wild-type mice, diabetic Plin5-KO mice lacked detectable LDs in the heart and did not exhibit aberrant lipid accumulation, excessive reactive oxygen species (ROS) generation, or heart malfunction. Moreover, diabetic Plin5-KO mice exhibited lower heart levels of lipotoxic molecules, such as diacylglycerol and ceramide, than wild-type mice. Membrane translocation of protein kinase C and the assembly of NADPH oxidase 2 complex on the membrane were also suppressed. The results suggest that diabetic Plin5-KO mice are resistant to type 1 diabetes-induced heart malfunction due to the suppression of the diacylglycerol/ceramide-protein kinase C pathway and of excessive ROS generation by NADPH oxidase.

引用

页码：2721 / 2731

页数：11

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