Research sheds light on why not all obese patients develop type 2 diabetes

Research sheds light on why not all obese patients develop type 2 diabetes

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Researchers at Oregon State University have devised a new analytical method that sheds light on an enduring puzzle of type 2 diabetes: why some obese patients develop the disease and others do not.

Type 2 diabetes is a serious metabolic disease that affects approximately one in 10 Americans. Formerly known as adult-onset diabetes, this is a chronic condition that affects the way the body metabolizes glucose, the sugar that is a major source of energy. This type of diabetes is often associated with obesity.

For some patients, this means that their bodies are not responding properly to insulin – it is counteracting the effects of insulin, the hormone produced by the pancreas that opens the door for sugar to enter cells. In the later stages of the disease, when the pancreas is depleted, patients do not produce enough insulin to maintain normal glucose levels.

In either case, sugar builds up in the bloodstream, and if left untreated, the effect weakens many major organs, sometimes to disabling or life-threatening degrees. The main risk factor for type 2 diabetes is being overweight, often the result of eating too much fat and sugar along with low physical activity.

Andrey Morgun and Natalia Shulzhenko of OSU and Giorgio Trinchieri of the National Cancer Institute have developed a new analytical technique, multi-organ network analysis, to explore the mechanisms underlying early-stage systemic insulin resistance.

Scientists have sought to find out which organs, biological pathways, and genes play roles.

Findings showing that a specific type of gut microbe gives rise to white adipose tissue containing macrophages — large cells that are part of the immune system — linked to insulin resistance, are published in Journal of Experimental Medicine.

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

Morgon, assistant professor of pharmaceutical sciences at Cairo University, said: “Our experiments and analyzes predict that a high-fat/sugar diet acts primarily in white adipose tissue by inducing microbe-related damage in energy synthesis, leading to resistance systemic insulin”. OSU College of Pharmacy. “Therapies that modify a patient’s microbiota in ways that target insulin resistance in adipose tissue macrophages could be a new treatment strategy for type 2 diabetes.”

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

Morgun and Shulzhenko, associate professor at Ohio State University’s Carlson College of Veterinary Medicine, have developed a computational method, Cross-City Network Analysis, which predicts which specific types of bacteria control the expression of mammalian genes associated with certain medical conditions such as diabetes.

“Type 2 diabetes is a global pandemic, and the number of diagnoses is expected to continue to increase over the next 10 years,” Chulzenko said. “The so-called Western diet – rich in saturated fats and refined sugars – is one of the key factors. But gut bacteria have an important role in mediating the effects of the diet.”

In the new study, the scientists relied on both cross-city network analysis and multi-member network analysis. They also conducted experiments on mice, looking at the gut, liver, muscle and white adipose tissue, and examining the molecular signature – in which genes are expressed – of white adipose tissue macrophages in obese human patients.

“Western diet-induced diabetes is characterized by germ-dependent mitochondrial damage,” Morgon said. “Adipose tissue has a predominant role in systemic insulin resistance, and we have characterized a gene expression program and a major major regulator of adipose tissue macrophages associated with insulin resistance. We discovered that the oscillator microbe, enriched with the Western diet, causes an increase in macrophages in insulin-resistant adipose tissue.”

The researchers add, however, that Oscillibacter is likely not the only microbial regulator of expression of the key gene they identified – Mmp12 – and that the Mmp12 pathway, while clearly functional, is probably not the only pathway of interest, depending on the current gut microbiota.

“We have previously shown that Romboutsia ilealis worsens glucose tolerance by suppressing insulin levels, which may be relevant to more advanced stages of type 2 diabetes,” Shulzhenko said.

Research shows that certain beneficial organisms can play a key role in treating type 2 diabetes

more information:
Zhipeng Li et al, Microbial damage and adipocytes are associated with mitochondria in type 2 diabetes by Mmp12+ macrophages, Journal of Experimental Medicine (2022). DOI: 10.1084 / jem.20220017

Provided by Oregon State University

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2022-06-04 08:17:01

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