15.09.2019 - By Dr Jyotsna Verma

How are obesity and diabetes related?

The death of fat cells in excess weight stimulates an immune inflammatory response, which, in turn, can lead to diabetes. Overweight is very often accompanied by type 2 diabetes, when our cells stop absorbing insulin, despite the fact that the pancreas continues to synthesize it properly. Due to insulin resistance, body tissues stop absorbing glucose from the blood, and a person has a lot of metabolic problems. Adipose tissue cells. (Photo by Dr. Fred Hossler / Visuals Unlimited / Corbis.) The lipid reserve occupies almost the entire volume of fat cells. (Photo by Dr. Alvin Telser / Visuals Unlimited / Corbis.) ›Open full size But how are overweight and diabetes related? It is believed that through the immune system, or rather, through an inflammatory reaction: obesity provokes inflammation, and it leads to problems with metabolism. But then another question arises: how exactly does all this happen? What molecular signals and processes are involved here? It is known that, when overweight, a lot of fat cells die and collapse (and they are replaced by new ones, in even greater numbers). Then it turns out that there should be a lot of cellular DNA in the blood. Indeed, researchers from Tokushima University and the University of Tokyo found that obese mice accumulate a lot of free DNA, and its accumulation occurs simultaneously with an increase in blood glucose (which is a sign of diabetes). Moreover, DNA from dead cells was often not found anywhere, but in immune cells of macrophages wandering around adipose tissue.

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How could such DNA be dangerous? As we know, immunity recognizes traces of infection. Infection, whether it be bacteria, viruses or some other pathogens, destroys and destroys our cells. In other words, free DNA serves the immune system as a signal that an emergency has developed somewhere. Experiments Masataka Sata ( Masataka Sata ) and his colleagues showed that the adipose tissue of mice are kept on a diet of fat, increased synthesis TLR9 receptor, which is just catches exogenous (i.e., the free, extracellular) DNA; and especially a lot of TLR9 was in immune macrophages. The more such DNA was, the more the receptor protein appeared: in experiments with cell culture of macrophages, it was seen how the level of TLR9 increases along with an increase in the level of DNA. In response to a pathogenic threat, these cells trigger an inflammatory reaction (which, generally speaking, serves as a powerful weapon against bacteria, etc.). In an article in Science Advances, the authors write that in response, macrophages stimulated by external DNA were prone to inflammation - that is, the death of adipocytes (fat cells) can actually provoke an inflammatory reaction with all the ensuing consequences. If TLR9 receptors were somehow turned off in obese mice, the intensity of the inflammatory signals decreased, and, most importantly, the sensitivity of tissues to insulin was restored - that is, the diabetic symptoms were alleviated. If then such animals were injected with stem cells, from which normal macrophages with working TLR9 were obtained, then everything became as usual - inflammation and insulin resistance returned.

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Of course, free DNA is hardly the only bridge linking obesity with diabetes. For example, two years ago, Cell Metabolism published an article in which the emphasis was on the protein RBP4 (retinol-binding protein 4), known as a carrier of vitamin A. Excessive fat stores somehow increase the level of RBP4, and he, in turn, activates immune tree cells and all the same macrophages - and again everything ends with inflammation. On the other hand, in the same 2014, we wrote that the probability of metabolic disorders in obesity depends on the hemoxygenase-1 enzyme, which regulates the strength of inflammation . Obviously, immune cells perceive several inflammatory signals at once, and now it remains to understand why such signals are activated when overweight. For example, in the case of the death of adipocytes, we do not yet know why they begin to die actively with the appearance of excess fat. But, one way or another, now you can try to look for some tool that, acting on the receptors of macrophages of adipose tissue, would suppress their inflammatory strivings: being overweight is unlikely to help lose weight, but it’s completely possible to reduce the risk of diabetes associated with it.

For Cure, Reversal and Treatment of Diabetes, Immediately Contact Dr Jyotsna Verma at Whatsapp +91 9266782222

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This Article was originally published on 15.09.2019 and updated most recently on 09.09.2025

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