Gene That Regulates Fat Accumulation Identified

In vivo studies showed that knockout mice lacking Panx1 genes accumulated greater total fat mass whether they were fed normal or high diets; absence of Panx1 also led to increased insulin and blood glucose levels increasing the risks for type 2 diabetes, in the first study to show a link between fat accumulation and Panx1.

Latest figures suggests that 10% of the global population is now obese according to W.H.O, which accounts for comorbidities including type 2 diabetes, cancers, and cardiovascular disease. Adipocytes that form from ASCs are the main type of cells that accumulates fat within the body, these cells have ability to store lipids that leads to excess adipose tissue formation. Obesity is a leading cause of death globally, and has reached epidemic proportion and continues to grow.

Channels are formed between cell surfaces and intracellular compartments by pannexin proteins that are also involved with cell signalling. Of these proteins Panx1 is reported to regulate cell proliferation and differentiation during early development in many cell types, however its function in early adipogenic development is poorly understood.

The team’s latest studies have confirmed that Panx1 knockout mice accumulated 42% more fat mass than normal, and the animals were more active and slept less; the animals did not gain more weight under intense high fat diets which may be due to increased activity. When Panx1 was missing from ASCs proliferation in their cultures was compromised with a 50% reduction in total cell numbers. In vivo studies suggest lack of Panx1 was associated with increased adipocyte fat cells in subcutaneous fat pads of knockout mice under normal and high fat diets.

The team suggests that their study shows Panx1 regulates proliferation and differentiation of ASCs into mature adipocytes, and germline deletion of Panx1 in ASCs lead to increased adipogenic differentiation and fat accumulation; use of knockout mice with germline depletion allowed for assessment of the gene’s role during the earliest stages of adipogenesis allowing observation in vivo and in vitro studies.

There is more hypertrophy in mice without Panx1 making fat cells larger and accumulate more fat. The team wants to look at levels of expression in human fat cells in the next phases of study to examine for the presence of mutations in samples from obese subjects vs healthy body weight subjects. Their early results are already starting to show connections, according to the researchers.