Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/12/2013
Publication Date: 5/1/2013
Citation: Mcmanaman, J.L., Bales, E.S., Orlicky, D.J., Jackman, M., Maclean, P.S., Cain, S., Crunk, A.E., Mansur, A., Graham, C.E., Bowman, T.A., Greenberg, A.S. 2013. Perilipin-2 null mice are protected against diet-induced obesity, adipose inflammation, and fatty liver disease. Journal of Lipid Research. 54(5):1346-1359. Interpretive Summary: The protein perilipin2 (plin2) is expressed on the surface of stored fat within all cells of the body. To investigate the role of plin2 in regulating body weight in response to a high caloric diet, we bred a mouse that does not express the plin2 gene or protein in any of its cells. We then fed a high caloric diet to the mouse that did not express plin2 and a normal mouse expressing plin2. We observed that the mice expressing plin2 ingested a significantly reduced amount of the high caloric diet and stored significantly less fat in its body as compared to a normal mouse. These data suggest that plin2 regulates appetite and body weight when consuming high caloric diet and protects against the development of obesity.
Technical Abstract: The cytoplasmic lipid droplet (CLD) protein perilipin-2 (Plin2) is expressed in multiple nonadipose tissues, where it is thought to play a role in regulating their lipid storage properties. However, the extent to which Plin2 functions in nutrient utilization and metabolism, or how it influences the consequences of over-feeding, remains unclear. In this study, we demonstrate that the absence of Plin2 prevents high-fat diet(HFD)-induced obesity in male and female mice. This response is associated with increased formation of subcutaneous beige adipocyte cells with uncoupling protein 1 expression, and amelioration of inflammatory foci formation in white adipose tissue and steatosis in the liver. Experiments demonstrate that Plin2 loss results in reduced energy intake and increased physical activity in response to HFD feeding. Our study provides the first evidence that Plin2 contributes to HFD-induced obesity by modulating food intake, and that its absence prevents obesity-associated adipose tissue inflammatory foci and liver steatosis.