title: Deficiency of a lipid droplet protein, perilipin 5, suppresses myocardial lipid accumulation, thereby preventing type 1 diabetes-induced heart malfunction.
abstract: 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.
authors.forename: Kenta
authors.initials: K
authors.lastname: Kuramoto
authors.forename: Fumie
authors.initials: F
authors.lastname: Sakai
authors.forename: Nana
authors.initials: N
authors.lastname: Yoshinori
authors.forename: Tomoe Y
authors.initials: TY
authors.lastname: Nakamura
authors.forename: Shigeo
authors.initials: S
authors.lastname: Wakabayashi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kojidani
authors.forename: Tokuko
authors.initials: T
authors.lastname: Haraguchi
authors.forename: Fumiko
authors.initials: F
authors.lastname: Hirose
authors.forename: Takashi
authors.initials: T
authors.lastname: Osumi
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000150:complications / Q000517:prevention & control*; D002518:Ceramides / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D004075:Diglycerides / Q000378:metabolism; D066292:Lipid Droplets / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D000070797:Perilipin-5; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013311:Streptozocin; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D002518:Ceramides; D004075:Diglycerides; D008562:Membrane Glycoproteins; D000070797:Perilipin-5; C511805:Plin5 protein, mouse; D011506:Proteins; D017382:Reactive Oxygen Species; D014280:Triglycerides; D013311:Streptozocin; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D011493:Protein Kinase C