Why not all obese patients develop diabetes

Obesity, often the result of eating too much fat and sugar coupled with low physical activity, is known to be a key factor in developing type 2 diabetes. However, some obese people do not develop the disease that affects millions of people worldwide. Turns out their gut bacteria play a role.

Andrey Morgun and Natalia Shulzhenko of Oregon State University and Giorgio Trinchieri of the National Cancer Institute developed a new analytical technique, multi-organ network analysis, to investigate the mechanisms behind early-stage systemic insulin resistance.

The findings, published in the Journal of Experimental Medicine, showed that a certain type of gut microbe leads to white adipose tissue that contains macrophage cells, large cells that make up the immune system, associated with insulin resistance.

In the human body, white adipose tissue is the main type of fat.

“Our experiments and analyzes predict that a high-fat/sugar diet acts primarily in white adipose tissue by causing microbiota-related damage to the energy synthesis process, leading to systemic insulin resistance,” said Morgun, an associate professor of pharmaceutical sciences in the OSU College of Pharmacy.

“Treatments that alter a patient’s microbiota in ways that target insulin resistance in adipose tissue macrophage cells may represent a novel therapeutic strategy for type 2 diabetes,” he added.

The human gut microbiome contains more than 10 trillion microbial cells from approximately 1,000 different bacterial species.

“The so-called ‘western diet,’ rich in saturated fats and refined sugars, is one of the most important factors. But gut bacteria play an important role in mediating the effects of diet,” Shulzhenko said.

In experiments in mice, looking at the gut, liver, muscle and white adipose tissue, the team found that “adipose tissue plays a predominant role in systemic insulin resistance.”

Furthermore, “they found that the Oscillibacter microbe, enriched by a Western diet, causes an increase in the insulin-resistant adipose tissue macrophage”.

However, the researchers add that Oscillibacter is probably not the only microbial regulator for expression of the key gene they identified, Mmp12, and that the Mmp12 pathway, while clearly instrumental, is probably not the only major pathway, depending on which one. gut microbes Gift.

Previous studies have shown that another microbial species “Romboutsia ilealis impairs glucose tolerance by inhibiting insulin levels, which may be relevant for more advanced stages of type 2 diabetes,” Shulzhenko said.

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