WCM-Q research probes mechanisms of premature aging of fat cells in obesity

WCM-Q research probes mechanisms of premature aging of fat cells in obesity

Researchers at Weill Cornell Medicine-Qatar (WCM-Q) have gained new insight into the molecular mechanisms by which obesity leads to premature aging of fat cells, and then to chronic inflammation, insulin resistance and – eventually - type-2 diabetes. The researchers, led by WCM-Q’s Dr. Nayef Mazloum, developed a new in vitro laboratory test and used gene analysis and editing technologies to discover key molecules that regulate cellular senescence and aging in adipose (fat) cells and examined the function of two protein encoding genes - named STAT1 and STAT3 - in the regulation of inflammation that can lead to insulin resistance and type 2 diabetes. Cellular senescence is a process of deterioration akin to aging in which cells lose certain functions, particularly the ability to proliferate by cell division.   Obesity and type-2 diabetes are two of the most pressing health issues facing Qatar. An estimated 41% of adult Qatari nationals are obese, compared to 13% worldwide. The global prevalence of type-2 diabetes among adults is around 10%, while in Qatar it is estimated that round 17% of adults have the condition, a figure that is projected to rise to 24% by 2050 if current trends continue. While it is already well known that obesity causes premature aging of cells within the adipose tissue that can lead to inflammation and diabetes, the molecular mechanisms underlying this cellular dysfunction remain poorly understood. In order to examine these molecular mechanisms, the WCM-Q researchers devised a new laboratory test whereby they employed murine fat cell precursors (preadipocytes) and exposed them to repeated cycles of sublethal doses of hydrogen peroxide to induce premature aging, which triggered the release of inflammatory molecules. The researchers were then able to use WCM-Q’s advanced capabilities in transcriptome analysis to discover which genes were being expressed to produce the inflammation and identify disease-specific molecules involved in regulating the inflammatory pathways. Additionally, the team used CRISPR gene editing technology to delete the protein-encoding STAT1 and STAT3 genes in order to examine the effects of these genes on inflammation of the adipose cells.