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Inactivation of Plin4 downregulates Plin5 and reduces cardiac lipid accumulation in mice
Weiqin Chen1, Benny Chang, Xinyu Wu
1Diabetes and Endocrinology Research Center, Section of Diabetes and Endocrinology, Departments of Medicine, Molecular and Cellular Biology and Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Abstract:
Plin4 is a lipid droplet protein (LDP) found predominantly in white adipose tissue (WAT). The Plin4 gene is immediately downstream of the Plin5 gene; the two genes exhibit distinct though overlapping tissue expression patterns. Plin4 is absent in brown adipose tissue (BAT) and liver and expressed at low levels in heart and skeletal muscle, whereas Plin5 is highly expressed in these oxidative tissues but at a low level in WAT. The physiological role of Plin4 remains unclear. We have generated Plin4(-/-) mice by gene targeting. Loss of Plin4 has no effect on body weight or composition or on adipose mass or development. However, the triacylglycerol (TAG) content in heart, but not other oxidative tissues such as BAT, soleus muscle, and liver, is markedly reduced in Plin4(-/-) mice. The heart of Plin4(-/-) mice displays reduced Plin5 mRNA and protein levels (by ~38 and 87%, respectively, vs. wild-type) but unchanged mRNA levels of other perilipin family genes (Plin2 and Plin3) or genes involved in glucose and lipid metabolism. Despite reduced cardiac TAG level, both young and aged Plin4(-/-) mice maintain normal heart function as wild-type mice, as measured by echocardiography. Interestingly, Plin4 deficiency prevents the lipid accumulation in the heart that normally occurs after a prolonged (48-h) fast. It also protects the heart from cardiac steatosis induced by high-fat diet or when Plin4(-/-) mice are bred into Lep(-/-) obese background. In conclusion, inactivation of Plin4 downregulates Plin5 and reduces cardiac lipid accumulation in mice.
Insights
Plin4 deficiency in mice reduces cardiac lipid accumulation and heart triacylglycerol content by downregulating Plin5. This finding clarifies the physiological role of Plin4 in lipid metabolism.
Area of Science:
- Biochemistry
- Molecular Biology
- Physiology
Background:
- Plin4 is a lipid droplet protein (LDP) primarily found in white adipose tissue (WAT).
- Plin4 and Plin5 genes exhibit distinct yet overlapping tissue expression patterns.
- The physiological function of Plin4 is not well understood.
Purpose of the Study:
- To investigate the physiological role of Plin4.
- To determine the impact of Plin4 deficiency on lipid metabolism and cardiac function in mice.
Main Methods:
- Gene targeting to generate Plin4 knockout (Plin4(-/-)) mice.
- Analysis of body composition, adipose mass, and tissue triacylglycerol (TAG) content.
- Measurement of cardiac function using echocardiography.
- Assessment of gene and protein expression levels in Plin4(-/-) mice.
Main Results:
- Plin4 deficiency did not affect body weight, composition, or adipose mass.
- Cardiac TAG content was significantly reduced in Plin4(-/-) mice.
- Plin4(-/-) mice exhibited reduced Plin5 mRNA and protein levels in the heart.
- Plin4 deficiency protected against diet-induced and fasting-induced cardiac steatosis.
- Cardiac function remained normal in Plin4(-/-) mice despite altered lipid content.
Conclusions:
- Inactivation of Plin4 leads to the downregulation of Plin5.
- Plin4 deficiency reduces cardiac lipid accumulation in mice.
- Plin4 plays a role in regulating cardiac lipid metabolism and preventing steatosis.
