Researchers at Weill Cornell Medicine-Qatar (WCM-Q) have made new discoveries about the essential role played by a protein called Sirtuin1 in the metabolism of fat, and how depletion of this protein is related to obesity and type-2 diabetes.

The researchers showed that the Sirtuin1 protein, also known as SIRT1, performs a wide variety of important functions, including promoting the metabolism of fat cells, coordinating the generation of healthy new fat cells from stem cells, regulating the function of key metabolic transcription factors, and facilitating the transcription of RNA from DNA to set other key metabolic functions in motion.

The research team, led by Dr. Nayef Mazloum, assistant professor of microbiology and immunology and assistant dean for student research at WCM-Q, was also able to show that SIRT1 promotes the biogenesis of mitochondria and facilitates the respiration of fat cells, which is required for fat to be broken down and expelled from the body as carbon dioxide via the lungs.

Moreover, SIRT1 promotes the expression of molecules such as leptin, a hormone involved in energy regulation and inhibition of hunger; glutathione s-transferase A3 (GSTA3), a family of enzymes involved in defense against toxic and carcinogenic compounds; and lipocalin 2 (LCN2), which sequesters iron and prevents it being used by bacteria, thus limiting their growth.

The researchers were able to identify these molecular pathways that are dependent on the SIRT1 protein by applying an advanced technique called quantitative proteomics analysis to adipose cells derived from mouse cells.

They were also able to discover that depletion of SIRT1 was associated with dysfunction of the fat cells, leading to increased levels of markers of inflammation and fibrosis of white adipose tissue.

Dr. Mazloum said, “Our latest research shows us in far greater detail why SIRT1 is such an important protein in human metabolism and metabolic health, playing a key role in many molecular pathways. It also underlines that obesity is not just about the accumulation of higher levels of stored fat in the body, but that it can also have negative effects on hormone regulation, cellular health, normal fat storage and metabolism, and control of inflammation.

“We believe that SIRT1, therefore, provides us with a very useful target for further research which might ultimately help in the development of new therapies to manage or prevent conditions related to obesity, such as type-2 diabetes,” he added.

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Cover Image Credit & Source: Gulf Times