Scientists at the University of Western Ontario have identified glycoprotein, Pannexin 1 (Panx1), which plays a key role in regulating the formation of adipocytes and fat accumulation. In vivo Studies have shown that chicken mice who do not have the Panx1 gene from the early development phase have accumulated a much greater weight compared to wild-type mice (WT), regardless of whether they were fed with a normal diet or high fat. The absence of Panx1 protein led to an increase in insulin and blood glucose levels, which increased the risk of type 2 diabetes.
Reporting in Scientific reportsthe team says that findings suggest Panx1 as a key ingredient in regulating fat accumulation and a "potential new target for overcoming obesity".
"This tells us that if you have to erase it in mice or lose functional mutations in humans, which makes Panx1 an irregular work, then you may be prone to accumulating more fat," commented Silvia Penuela, PhD, assistant professor at Western Schulich School of Medicine & Dentistry, and a leading author of the study team. "This is the first study that shows the link between Panx1 and fat accumulation." The results are described in the article entitled "Pannexin 1 regulates the differentiation of fatty stromal cells and the accumulation of fat."
The "Obesity Epidemic" is the leading cause of death worldwide, with WHO figures suggesting that about 10% of the world's population is now obese, writes the authors. Obesity also causes co-morbidity, including type 2 diabetes, cancer and cardiovascular disease. Adipocytes, formed from differentiated stromal cells derived from fats (ASCs), are the major cell type that collects fat in the body. These cells have the innate ability to store lipids, which leads to excessive formation of fat tissues.
Pannexin's proteins (Panx1, Panx2, and Panx3) are a family of glycoproteins that form channels between the cell surface and intracellular compartments, so they are involved in cell signaling. Panx1 has been reported to regulate cell proliferation and differentiation in many different cell types during early development, but its function in the early development of adipogenesis is not understood.
The preliminary work of the Ontario team of the Ontario team using the Panx1 knockout (KO) mouse model showed that mice that do not have a gene develop an increased fatty layer four days after birth and continue in adulthood. Based on these findings, the group assumed that Panx1 can regulate the proliferation and differentiation of adipogenic cells, leading to changes in the accumulation of fat.
Their most recent studies first confirmed that Panx1 KO mice accumulated 42% more fat than usual, WT mice. Interestingly, when both groups of mice were fed with high fat content (HFD), Panx1 KO animals accumulated more fat than WT animals, but they gained weight at the same rate as WT controls. A further investigation showed that Panx1 KO animals were more active and burned less than WT controls, which may have explained why they did not give more weight. "… KO mice do not gain more weight under an intense diet with high fat content, which may be due to their increased activity and decreased sleep compared to their colleagues from WT," explains the researchers. There were no significant differences in the activities and sleeping stages of WT and Panx1 KO animals that were fed with normal diet.
Additional studies confirmed that Panx1 was expressed in ASCs in WT animals and showed that when Panx1 is missing from ASC, their spread in culture is compromised, "… with approximately 50% reduction in the total number of cells compared to WT ASCs. .. ". "… Panx1 KP ASCs much slower than WT ASCs, but there was no effect on cell death."
Further analyzes have shown that the term Panx1 is parallelized by induction of adipogenesis in WT ASC. When WT and Panx1 KO ASCs were cultivated in culture and caused adipogenic differentiation, Panx1 KO cells collected more intracellular lipids than WT ASCs. In vivo Studies have shown that the lack of Panx1 is associated with an increased surface of adipocyte cells, indicating hypertrophy or excessive growth of individual fat cells in the subcutaneous fat Panx1 KO mice in both conventional diets and high fat regimens. The numbers of adipocytes were fed with normal diet in the Panx1 KO fat lips. "In the case of high-fat diet, a similar trend was observed in a small number of adipocytes Panx1 KO, but it was not statistically significant," wrote the authors.
They say that their study for the first time showed that "Panx1 regulates the spread and differentiation of ASCs in mature adipocytes and that the deletion of the Panx1 embryo in ASC leads to increased adipogenous differentiation and fat accumulation." The use of Panx1 KO Mice with germline germline exhaustion also made it possible to evaluate the role of the gene in the earliest stages of adipogenesis, "where it was observed that the lack of Panx1 in cells similar to parent progenitors significantly influenced the proliferation and differentiation in vitro, and fat accumulation in vivo. "
"When mice do not have Panx1, there is more hypertrophy, so their fat cells are much larger and more fat accumulates," Dr. Penuela. "The next step in our study is to review the level of Panx1 expression in human fat cells and to study the presence of potential mutations in the Panx1 gene in samples taken from patients who are obese compared to donors with a healthy body weight. In the early days of this study we are already starting display a link. "