March 26, 2023

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Why don’t all obese people get type 2 diabetes?

Why don’t all obese people get type 2 diabetes?


Why don’t all obese people get type 2 diabetes? 

A new analytical technique developed by researchers at Oregon State University sheds light on a long-standing mystery of type 2 diabetes: why some obese people get the disease while others don’t.


One in 10 Americans has type 2 diabetes, a serious metabolic disease.

This is a disease that affects how the body metabolizes glucose, a major source of energy. The disease used to be called adult-onset diabetes.

This type of diabetes is often associated with obesity.


For some people, this means their body isn’t responding to insulin as it should. Instead, it is resistant to the action of insulin.

Insulin is a hormone produced by the pancreas that helps sugar enter cells. When the pancreas is worn down in the later stages of the disease, individuals cannot produce enough insulin to keep their blood sugar levels within the normal range.


In both cases, blood sugar levels rise, and if ignored, the consequences can weaken several vital organs — sometimes seriously and even fatally. Being overweight, usually caused by eating too much fat and sugar combined with little physical activity, is a major risk factor for type 2 diabetes.


To study the processes behind early systemic insulin resistance, Andrey Morgun, Natalia Shulzhenko and Giorgio Trinchieri of the National Cancer Institute created a new type of analysis called multi-organ network analysis. Scientists want to know which organs, biological pathways and genes are involved.


The findings, published in the Journal of Experimental Medicine , demonstrate how a certain gut microbe causes white adipose tissue to contain macrophages — large immune system cells associated with insulin resistance. In the human body, white adipose tissue is the main type of fat.


Why don't all obese people get type 2 diabetes?


“Our experiments and analyses predict that a high-fat/high-sugar diet acts primarily on white adipose tissue, driving impairment of microbiota-related energy synthesis processes, leading to systemic insulin resistance,” said Morgun, associate professor of pharmaceutical sciences in OSU’s College of Pharmacy. “Therapies that alter a patient’s microbiome in a way that targets insulin resistance in adipose tissue macrophages may represent a new therapeutic strategy for type 2 diabetes.”


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


Morgun and Shulzhenko, an associate professor at OSU’s Carlson School of Veterinary Medicine, developed a computational approach, transkingdom network analysis, in earlier research to predict the specific types of bacteria that control the expression of mammalian genes associated with specific diseases, such as diabetes.


“Type 2 diabetes is a global epidemic and the number of diagnoses is expected to continue to increase over the next 10 years. The so-called ‘Western diet’ – high in saturated fat and refined sugar – is one of the main factors,” Shulzhenko said. …but gut bacteria play an important role in mediating the effects of diet.”


In the new study, the scientists relied on transkingdom network analysis and multi-organ network analysis. They also performed experiments in mice, looking at the gut, liver, muscle and white adipose tissue, and examined the molecular signature of white adipose tissue macrophages — which genes are being expressed — in obese human patients.


“Diabetes induced by a Western diet is characterized by microbiota-dependent mitochondrial damage,” Morgun said. “Adipose tissue plays a dominant role in systemic insulin resistance, and we have a detailed understanding of the gene expression program of adipose tissue macrophages and insulin resistance-related effects.” Key master regulators were characterized. We found that Oscillibacter microbes enriched in the Western diet lead to an increase in insulin-resistant adipose tissue macrophages.”


However, the researchers add that it is likely that Oscillibacter is not the only microbial regulator of expression of the key gene they identified — Mmp12 — and that the Mmp12 pathway, while clearly functioning, may not be the only important pathway, depending on which gut presence of microorganisms.


“Our previous study showed that Romboutsia ilealis worsens glucose tolerance by suppressing insulin levels, which may be associated with more advanced stages of type 2 diabetes,” said Shulzhenko.





Why don’t all obese people get type 2 diabetes?

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