Why chronic inflammation makes you fat and diabetic (and vice versa)

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Why chronic inflammation makes you fat and diabetic and vice

Diabesity is an inflammatory autoimmune disorder. In this article, we will review the evidence linking Chronic inflamation with obesity and type 2 diabetes and learn why inflammation may be the most important mechanism driving the diabesity epidemic.

The inflammation-diabesity connection is a hot topic in the scientific literature. A Pubmed search for “inflammation, diabetes, obesity” shows over 1,800 articles. The association between these conditions has been known for decades. In fact, high doses of salicylates, a class of anti-inflammatory compounds that includes aspirin, were used to treat type 2 diabetes more than 100 years ago.

In 1876, a doctor named Ebstein discovered that sodium salicylate could make the symptoms of diabetes completely disappear. (In case you’re wondering why doctors don’t use this therapy today, it fell out of favor due to serious side effects caused by high doses of salicylates.)

Although the association between chronic inflammation and diabesity is well knowndoubts remain. Does diabesity cause inflammation or does inflammation cause diabesity? How and why does the body initiate an inflammatory response to diabesity? Does obesity itself cause inflammation, or is the inflammation caused by something secondary to obesity (such as high blood sugar or triglycerides)?

How Chronic Inflammation Causes Diabesity

There are several lines of evidence that chronic inflammation directly causes obesity and diabetes.

Inflammation as a predecessor of diabesity

First, inflammation has been shown to precede the development of diabesity. Elevated levels of inflammatory cytokines predict future weight gain, and infusion of inflammatory cytokines into normal-weight healthy mice causes insulin resistance.

The idea that inflammation precedes diabesity is supported by the observation that humans with other chronic inflammatory conditions are at increased risk of developing type 2 diabetes.

For example, about a third of patients with chronic hepatitis C develop type 2 diabetes, and those with rheumatoid arthritis are also at increased risk.

Inflammation begins in fat cells

Second, the inflammation starts in the fat cells themselves. Fat cells are the first to be affected by the development of obesity. As the fat mass expands, inflammation increases. One mechanism for this may be dysfunction of the mitochondria (the “power plant” of our cells) caused by the additional stress that obesity places on cellular function.

Another mechanism may be oxidative stress. As more glucose is delivered to fat cells, excess reactive oxygen species (ROS) are produced, which in turn initiates an inflammatory cascade within the cell.

Chronic inflammation of adipose tissue causes insulin resistance

Third, inflammation of adipose tissue causes insulin resistance, which is the hallmark of type 2 diabetes. TNF-α, a cytokine (small protein) released during the inflammatory response, has been repeatedly shown to cause resistance. to insulin. Several other proteins involved with inflammation, such as MCP-1 and C-reactive protein, have also been shown to cause insulin resistance.

Brain inflammation causes resistance to hormone that regulates appetite

Fourth, inflammation of the brain (specifically the hypothalamus) leads to leptin resistance, which often precedes and accompanies insulin resistance and type 2 diabetes. Leptin is a hormone that regulates appetite and metabolism. It does this through its effect on the hypothalamus. When the hypothalamus becomes resistant to leptin, glucose and fat metabolism are affected, resulting in weight gain and insulin resistance.

Finally, inflammation of the intestine causes resistance to leptin and insulin. This can occur through an increase in lipopolysaccharide (LPS), an endotoxin produced by Gram-negative bacteria in the gut. LPS has been shown to cause inflammation, insulin resistance in the liver, and weight gain.

How Diabesity Causes Chronic Inflammation

Until relatively recently, fat was considered an inert tissue with no biological activity. The idea was that he was just, well, there. It didn’t do much more than store excess energy.

We now know, however, that adipose tissue is a metabolically active endocrine organ that secretes hormones and inflammatory cytokines such as IL-6 and TNF-α. The metabolic activity of fat is the key to understanding its role in diabesity.

Why would obesity cause inflammation? There are two basic theories.

Chronic inflammation induced by obesity prevention mechanism

The first is that obesity-induced inflammation is actually a protective mechanism that prevents the body from losing mobility or fitness. Fat storage is an anabolic process, which means it strengthens your organs and tissues.

Inflammation, on the other hand, is a catabolic process. Catabolism breaks down organs and tissues. It is possible that the activation of catabolism through inflammation is the body’s attempt to keep weight within acceptable limits. Evidence that experimentally induced local inflammation in adipose tissue improves insulin resistance and causes weight loss supports this theory.

Inflammation due to obesity is a malfunction

The second theory is that the obesity-induced chronic inflammation it is simply a malfunction that was never selected against in human evolution. Obesity and its related disorders have been extremely rare throughout human history and have only become common in the last 40 years.

The surplus of modern processed foods that accompanies diabesity is also a relatively new phenomenon. It’s possible that the stress of obesity is similar enough to the stress of an infection that the body reacts to obesity the same way it would to an infection: through inflammation. Supporting this theory is evidence that the same intracellular inflammatory stress pathways are activated in both obesity and infection.

Whichever theory is correct (and probably both are, to some extent), it is clear that diabesity causes inflammation. Insulin and leptin resistance alter glucose metabolism. When fat cells become insensitive to insulin, they cannot store more glucose and hyperglycemia results. Excess sugar in the blood causes glycation, a process in which a sugar molecule binds to a protein or fat, leading to the formation of advanced glycation end products (AGEs). AGEs are inflammatory and are associated with type 2 diabetes.

Obesity causes chronic inflammation due to genes involved

Obesity also contributes to inflammation by regulating certain genes involved in the inflammatory response. These genes control the expression of white blood cells called macrophages that play a key role in inflammation. As the concentration of macrophages in fat tissue increases, the release of inflammatory byproducts such as TNF-α, IL-6, and MCP-1 also increases. This means that the more fatty tissue you have, the more inflammation it will produce.

As we have seen, chronic inflammation is both the cause and the result of diabesity. Once obesity and/or insulin resistance have been established, each can further stimulate the production of inflammatory cytokines, forming a vicious cycle of inflammation and diabesity.

It follows, then, that the key to preventing and treating diabesity is to reduce inflammation. Unfortunately, few doctors treating diabesity today understand this. Focusing solely on regulating blood sugar and fat hormones without addressing other potential causes of inflammation will lead to inferior results.

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