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Research in vitro and in mouse models zooms in on the role macrophages may play in obesity-relared conditions. Image credit: VICTOR TORRES/Stocksy.
  • Researchers investigated how metabolic processes affect the function of certain immune cells that play a role in inflammation.
  • They found one particular metabolic pathway to be critical for the function of these immune cells and associated with processes involved in obesity-related conditions.
  • They hope their findings may lead the way to novel treatment options for obesity-related conditions.

Macrophages are a type of immune cell that can be found in most organs in the body. They remove harmful substances and dead cells from tissues, and contribute to homeostasis — stability among bodily systems.

Macrophages are metabolically plastic, meaning they can change their metabolism and function to match the needs of different organ environments. Their function may also be affected by changing environments.

For example, macrophages transition from a dormant to an inflammatory state in fatty tissue in obese individuals. This inflammatory state eventually contributes to conditions including metabolic syndrome, insulin resistance, and non-alcoholic fatty liver disease.

Understanding more about the link between cell metabolism and immune function could enable more treatment options for obesity.

Recently, researchers conducted cellular and mouse studies to understand the relationship between metabolism and function of these immune cells, and how they may be associated with obesity-related conditions.

“This latest research sheds new light on one piece of the puzzle of understanding obesity and inflammation,” Dr. Paul Chandler, bariatric surgeon with Novant Health in Winston-Salem, NC, not involved in the study, told Medical News Today.

“The study shows that impairing a certain immune cell’s ability to cause inflammation in fatty tissue prevents weight gain, metabolic syndrome, and fatty liver in mice,” he added.

The study appears in the journal Immunity.

To begin, the researchers analyzed genetic data from macrophage populations from 10 different human organs and from 10 different mouse organs.

They found that the oxidative phosphorylation (OP) metabolic pathway could explain differences among macrophages depending on their organ location. OP is the main energy-producing pathway among many cell types.

To understand whether these findings remained valid in vivo, the researchers observed the metabolic effects of deleting genes that enable OP in macrophages in mice.

In non-obese mice, deleting genes for OP increased cholesterol levels and cellular stress, and prompted cell cycle arrest, stopping cell division.

However, in obese mice, deleting the same genes reduced macrophages, and prevented insulin resistance and the build-up of fatty tissue in the liver.

Dr. Sue Decotiis, board-certified in Internal medicine, obesity medicine, and regenerative medicine, not involved in the study, told MNT:

“Macrophages, as focused on in this study, are only one factor in immune dysfunction in obese. The origin of immune dysfunction is still not known. Is it obesity that causes immune dysfunction or the reverse? What comes first- the chicken or the egg? We do know that treating obesity gets rid of immune dysfunction and inflammation.”

Dr. Sameer Murali, obesity medicine specialist with McGovern Medical School at UTHealth Houston, not involved in the study, also noted that “[o]n the case of obesity-related conditions, inflammation-promoting conditions occur at different BMI thresholds for different populations.”

“One current theory is that the proinflammatory environment in fat depots is mediated by a lack of oxygen in these areas, causing the fat cells to release proinflammatory signals, which in turn attracts proinflammatory macrophages,” he told us.

“This interaction between fat cells and macrophages in living tissue is difficult to study and would be important to clarify in order to better understand how these findings may be used to treat conditions that arise from chronic inflammation arising from fat tissue,” added Dr. Murali.

Dr. Mir Ali, bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, not involved in the study, pointed out that the use of a mouse model could mean the findings may not apply to humans.

“The study is conducted in an animal model and may not apply readily in human trials. Furthermore, the specific chemicals/medications needed to block specific macrophages are as yet not available,” he told us.

Prof. Philipp E. Scherer, professor in the Department of Internal Medicine at UT Southwestern Medical Center, not involved in the study, added that the researchers disrupted all macrophages in the system, making cause and effect in individual tissues hard to discern.

And Dr. Danine Fruge, medical director at Pritikin Longevity Center, not involved in the study, commented that “[w]e will need more research to define how the genetics may vary among different human populations, including age, race, sex at birth, coexisting medical conditions, etc.”

“We also need to develop safe genetic methods to further investigate the metabolism of individual cells in different human tissues as this study was limited to genetic manipulation in mice,” she added.

Dr. Abiona Redwood, core faculty of the Family Medicine Residency Program at Community Health of South Florida, not involved in the study, spoke to MNT about what made this study relevant:

“Within our society, which places such a premium on looking thin, there are factors that make weight loss especially challenging. These include hormonally-based challenges such as the difficulty post-menopausal women, older men, and teens going through puberty can face losing weight, or it can be a matter of eating foods that can make it difficult to lose weight given that healthy foods are more expensive and go bad sooner than unhealthy foods.”

“The pressure of society to lose weight, which takes a generally common problem and often places undue pressure on individuals about that problem, can place a heavy burden on those fighting to lose weight. Hopefully, the findings in this study can help lead to alternative means of addressing obesity-related diseases,” she added.