The Role of A Recently Discovered Protein in Obesity

Ellie Teng ‘21

obesity
Figure 1. PGRMC2 is a major contributor to the roles of hemes and thermogenesis.

Progesterone receptor membrane component 2 (PGRMC2) is a signaling protein found in various parts of the body including the uterus and liver. While it is highly expressed in fat tissue, it is also found in especially high levels in brown fat and is required for thermogenesis, the conversion of food into body heat. Researchers at the Scripps Research Institute took this knowledge and sought to expand on it by studying the role and functions of PGRMC2 in the human body. 

After conducting experiments with mice, scientists found that obese-diabetic and PGRMC2-null mice were prone to metabolic deterioration when fed a high-fat diet, while obese-diabetic mice treated with PGRMC2 activator experienced improvements in their conditions. These results suggested a role of PGRMC2 in intracellular heme transport, as the regulation of PGRMC2 levels may have affected obesity-linked defects in fat cells. PGRMC2 binds to and releases the heme molecule, supporting processes such as cellular respiration and proliferation. PGRMC2 is a heme stabilizer and supports its transport from the mitochondria to the nucleus. Mice without PGRMC2 present in their fat tissue were fed a high-fat diet and became intolerant to glucose and insensitive to insulin. The mice were treated with a drug that activated PGRMC2 function and  demonstrated an improvement over the diabetic symptoms. The mice regained glucose tolerance and experienced less resistance to insulin. Additionally, mice without the PGRMC2 gene were unable to efficiently regulate body temperature in cold environments. 

The heme molecule has a crucial role in mitochondrial functions and metabolism. By  activating or promoting the function of PGRMC2 , the “chaperone” for heme could mitigate the symptoms of metabolic disorders. This could improve the lives of many who suffer from non-alcoholic steatohepatitis (NASH), for which the solution is usually liver transplantation. Further research of this protein will allow for advancements in metabolic disease treatments. 

 

References:

  1. A. Galmozzi, et al., PGRMC2 is an intracellular haem chaperone critical for adipocyte function. Nature (2019). doi: 10.1038/s41586-019-1774-2

2. Image retrieved from: https://www.istockphoto.com/photo/young-female-doctor-measuring-waist-of-overweight-woman-with-centimeter-in-clinic-gm922754232-253302427?irgwc=1&esource=AFF_IS_IR_Du%C5%A1an%20Bi%C4%8Danski%20Pr%20Digitalnio_1404368&asid=Du%C5%A1an%20Bi%C4%8Danski%20Pr%20Digitalnio&cid=IS&utm_medium=affiliate&utm_source=Du%C5%A1an%20Bi%C4%8Danski%20Pr%20Digitalnio&utm_content=1404368&clickid=wLbVvD0fHxyOUpTwUx0Mo38VUkn1%3AKRu2Si0xg0

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