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Specific immune cells that contribute to inflammation may have links to obesity, according to a new study in the journal Science Translational Medicine. VICTOR TORRES/Stocksy Photo
  • A new study on obesity looks at the role of inflammation.
  • Researchers studied obesity levels in both wild mice and genetically modified mice.
  • They found that the genetically modified mice lacked the programmed death-ligand 1 (PD-L1) protein, which is involved in cell signaling in the immune system.
  • The study also found that mice lacking PD-L1 in certain types of cells gained more weight and had higher levels of inflammation.

With obesity levels in the United States on the rise, researchers are studying what contributes to this condition at a molecular level.

Researchers from Ireland and Germany believe they have isolated specific cells that contribute to the inflammation associated with obesity. Their study, which appears in the journal Science Translational Medicine, addresses how managing certain cell components can help reduce obesity and the risk of related diseases such as type 2 diabetes.

According to 2017–2018 data from the Centers for Disease Control and Prevention (CDC), obesity affected 42.4% of adults in the U.S.

Health experts consider people overweight when their body mass index (BMI) reaches 25 and obese with a BMI of 30.

Several factors contribute to obesity, including food consumption and activity levels, but researchers are increasingly calling into question the so-called energy balance hypothesis of obesity. Trauma, stress, and some medications, such as steroids, can also contribute to weight gain.

Inflammation is a contributing factor to obesity. There are two types of inflammation: acute and chronic.

Acute inflammation occurs during an injury or infection. The immune system releases cytokines that aid in healing.

However, chronic inflammation is long lasting and can occur when a person’s immune system is constantly overstimulated. When this occurs, certain functions in the body become dysregulated.

One major health issue relating to chronic inflammation is obesity.

Adipose tissue, or body fat, produces a type of cytokines. Health experts think an excessive amount of these proteins in people with obesity dysregulates the body, which could lead to metabolic disorders and heart disease.

“Fat has traditionally been thought of as a passive storage organ for excess energy, but over the past couple of decades, it has been increasingly understood to have a huge number of other roles involved in metabolic signaling,” Dr. Victoria Salem said in an interview with Medical News Today.

“It has a rich blood and nerve supply and a complex interaction with the hormonal and immune systems.”

Dr. Salem is a fellow in the Department of Bioengineering and an honorary consultant in Diabetes, Endocrinology, and General Internal Medicine at Victoria at Imperial College London.

The researchers speculated that the molecule PD-L1 plays a role in developing obesity. PD-L1 is a checkpoint protein involved in cell signaling within the immune system.

According to the authors, PD-L1 “regulates adipose tissue immune cell composition.”

“Increasing evidence demonstrates profound dysregulation of the immune system in people with obesity […] leading to a state of low-grade inflammation,” the authors write.

With this in mind, the researchers compared wild-type mice and mice genetically altered to lack PD-L1 in different types of cells, including dendritic, T cells, macrophages, and innate lymphoid cells. They fed both groups of mice a high fat diet and then compared which group had more weight gain.

They found that the mice lacking PD-L1 on their dendritic cells “gained significantly more weight after 12 weeks” on the high fat diet. This group also had increased insulin resistance, which leads to type 2 diabetes.

According to the authors, “These results clearly demonstrate a critical role of the immunoregulator PD-L1 for the control of obesity.”

“This new process of checkpoint regulation of cells in visceral fat of obese individuals advances our understanding of how the immune system controls diet-induced weight gain that can lead to conditions such as obesity and type 2 diabetes,” says study co-lead author Professor Padraic Fallon.

Prof. Fallon is the head of the Translational Immunology Group from Trinity College Dublin’s School of Medicine in Ireland.

After establishing the importance of PD-L1 in obesity with mice, the scientists accessed human studies and found that PD-L1 was “up-regulated” in people with obesity.

“Only through our basic research efforts using preclinical models were we able to gain access to patients’ samples and link our findings to human disease,” says co-lead author Dr. Christian Schwartz.

Dr. Schwartz is a principal investigator at University Hospital Erlangen in Germany.

The researchers hope that learning the importance of PD-L1 will factor into future weight loss treatments.

“It will be interesting to investigate now how we can manipulate this checkpoint on specific cell populations of interest to help people with obesity,” says Dr. Schwartz.

Dr. Mir Ali, a bariatric surgeon, spoke with MNT on the study findings.

“This article is interesting in that another physiological pathway to obesity seems to be clarified,” commented Dr. Ali. “Since obesity is a complex interaction of hormonal and metabolic interactions, this sheds light on another mechanism.”

In addition to being a surgeon, Dr. Ali is also medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, California.

Dr. Ali thinks the surgery could give hope to people with obesity in the future.

“Potentially, there is a possibility of finding a safe and effective medication that may block this pathway to obesity,” Dr. Ali said.