Birmingham obesity research could herald novel therapy

Researchers say the discovery could provide a novel therapy to reduce systemic inflammation and tissue damage that underpins the onset of multiple obesity-related conditions, or co-morbidities.

Dr Helen McGettrick of the university’s Institute of Inflammation and Aging described the investigation for which results were published in Clinical and Experimental Immunology. She explained:

“Obesity causes low-grade systemic inflammation, that alters the function of cells in the immune system and also stromal cells that are resident within tissues, increasing the risk of developing diseases in organs across the body.

“Despite this, we know very little about exactly how obesity induced inflammation drives pathology in non-adipose tissues.  We’ve shown a completely new therapeutic route, which could provide new drugs to tackle the root cause of the obesity-related conditions by preventing the damage caused by systemic inflammation.”   

Scientists employed used a mouse model of obesity to investigate whether PEPITEM – identified in 2015 by University of Birmingham researchers –could prevent or reverse the effects of a high fat diet (HFD) on insulin-producing cells in the pancreas and immune cell migration into various tissues.  

Results after six weeks of PEPITEM administration, with mice simultaneously fed HFD showed “significant reductions in the enlargement of pancreatic islet insulin-producing beta cells (stromal cells), the number of CD4+ T cells in the visceral adipose tissue and the peritoneal cavity, and the number of macrophages in the peritoneal cavity compared to controls”.  

Separately, mice were fed HFD for six weeks prior to implantation of slow-release pumps for an additional six weeks.  Here, the group also observed a reduce in the number of T and B-cells in the blood, with a concomitant increase in these cell types seen in secondary lymphoid tissues (spleen, inguinal lymph node). 

The investigators said this demonstrated that PEPITEM systematically modulated leukocyte trafficking through tissues, potentially reversing the effects of the obesogenic diet on these body compartments.  

McGettrick added: “Obesity is a global health challenge, with numbers of obese adults and children rising at an alarming rate, and many suffering from obesity-related co-morbidities. Collectively these conditions have an enormous impact on global economies, estimated at over 2% of global gross domestic product. 

“We have now shown that PEPITEM may provide a novel, alternative therapeutic strategy, which may be particularly beneficial in individuals at risk of obesity related diseases.”  

University of Birmingham Enterprise has filed patent applications covering PEPITEM compositions and therapeutic uses, with a further application filed covering its use in the use in the treatment of obesity-associated inflammatory conditions. 

Pic: Pranidchakan Boonrom