Isolated Plin5-deficient cardiomyocytes store less lipid droplets than normal, but without increased sensitivity to hypoxia.
Isolated Plin5-deficient cardiomyocytes store less lipid droplets than normal, but without increased sensitivity to hypoxia.
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DOI：
10.1016/j.bbalip.2020.158873
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发表时间：
2020-12
期刊：
影响因子：
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通讯作者：
Yuchuan Li;M. Torp;F. Norheim;P. Khanal;A. Kimmel;K. Stensløkken;J. Vaage;K. Dalen
中科院分区：
文献类型：
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作者：
Yuchuan Li;M. Torp;F. Norheim;P. Khanal;A. Kimmel;K. Stensløkken;J. Vaage;K. Dalen
Plin5 is abundantly expressed in the heart where it binds to lipid droplets (LDs) and facilitates physical interaction between LDs and mitochondria. We isolated cardiomyocytes from adultPlin5+/+andPlin5−/−mice to study the role of Plin5 for fatty acid uptake, LD accumulation, fatty acid oxidation, and tolerance to hypoxia. Cardiomyocytes isolated fromPlin5−/−mice cultured with oleic acid stored less LDs thanPlin5+/+, but comparable levels toPlin5+/+cardiomyocytes when adipose triglyceride lipase activity was inhibited. The ability to oxidize fatty acids into CO2was similar betweenPlin5+/+andPlin5−/−cardiomyocytes, butPlin5−/−cardiomyocytes had a transient increase in intracellular fatty acid oxidation intermediates. After pre-incubation with oleic acids,Plin5−/−cardiomyocytes retained a higher content of glycogen and showed improved tolerance to hypoxia compared toPlin5+/+. In isolated, perfused hearts, deletion of Plin5 had no important effect on ventricular pressures or infarct size after ischemia. OldPlin5−/−mice had reduced levels of cardiac triacylglycerides, increased heart weight, and apart from modest elevated expression of mRNAs for beta myosin heavy chainMyh7and the fatty acid transporterCd36, other genes involved in fatty acid oxidation, glycogen metabolism and glucose utilization were essentially unchanged by removal of Plin5. Plin5 seems to facilitate cardiac LD storage primarily by repressing adipose triglyceride lipase activity without altering cardiac fatty acid oxidation capacity. Expression of Plin5 and cardiac LD content of isolated cardiomyocytes has little importance for tolerance to acute hypoxia and ischemia, which contrasts the protective role for Plin5 in mouse models during myocardial ischemia.
