Important Points:

• Inflammation
• Obesity
• Diabesity
• Insulin resistance
• Adipose tissue

Understanding the role metabolic inflammation plays in obesity and diabesity

Obesity is a disease that has plagued the modern day man in recent time. Access to highly processed foods and decrease in physical activity are key contributors to this ailment. Researchers are hard at work looking into what other underlying factors lead to obesity, especially given its relationship with the onset of Type 2 Diabetes, Cardiovascular diseases, and liver disease. We will take an in-depth look at metabolic inflammation and its role in the onset of obesity. Let’s dive in.

1. What is Obesity?

Obesity is a state in which there is an over-accumulation of subcutaneous and/or abdominal fat (adipose tissue) characterized by a low grade chronic state of inflammation in which the level of pro inflammatory cytokines are increased.  This adipose tissue is no longer considered inert and mainly devoted to storing energy; it is emerging as an active tissue in the regulation of physiological and pathological processes including immunity and inflammation.

Obesity is diagnosed when your body mass index (BMI) is 30 or higher. To determine your body mass index, use one of these formulas:

BMI =  

For most people, BMI provides a reasonable estimate of body fat. Because BMI doesn’t directly measure body fat, some people such as muscular athletes may have a BMI in the obesity category even though they don’t have excess body fat.

2. What is Diabesity?

‘Diabesity’ is the term for diabetes occurring in the context of obesity. This form of obesity-dependent diabetes has emerged as a major public health problem in recent times. Though it is basically explained by insulin resistance and pancreatic beta cell dysfunction, new patterns have evolved to explain these modifications in the context of the modern rates of obesity and diabetes.

3. Is Obesity an Inflammatory Condition?

The connection between obesity and inflammation has been in debate in the recent past. Unbeknownst to many, the link between these conditions was made decades ago. Over a century ago, high doses of a class of anti-inflammatory compounds including aspirin (salicylates) were used to treat Type 2 diabetes. In some cases, the symptoms of diabetes totally disappeared. Unfortunately, this treatment was discontinued due to the serious side effects caused by the high doses of salicylates.

We will now look at the questions of our topic today in-depth; does obesity cause inflammation, or is inflammation caused by something secondary to obesity such as high blood sugar or triglycerides levels? How about diabesity? Does diabesity cause inflammation, or does inflammation cause diabesity? How and why does the body initiate an inflammatory response to diabesity? Let us tackle each item separately.

4. How Does Inflammation Cause Diabesity?

Listed are some lines of evidence that show inflammation directly causes obesity and diabesity.

• The development of diabesity has been shown to follow inflammation. Raised levels of inflammatory cytokines predict impending weight gain. In a study, infusion of inflammatory cytokines into healthy, normal weight mice caused insulin resistance. This concept is also illustrated by the fact that people with other chronic inflammatory conditions are at higher risk of developing Type2 Diabetes; for example, about one-third of chronic Hepatitis C patients develop Type 2 diabetes, and those with rheumatoid arthritis are also at higher risk.
• In obesity, inflammation has been noted to start in the fat cells themselves. As fat mass expands, inflammation increases. One explanation may be that dysfunction of the mitochondria (the “power plant” of our cells) caused by obesity puts increased stress on cellular function. Another mechanism may be oxidative stress. As more glucose is delivered to the fat cells, they produce an excess of reactive oxygen species (ROS) which in turn starts an inflammatory cascade within the cell.
• Inflammation of the fat tissue causes insulin resistance, which is the primary feature of Type 2 diabetes. TNF-α, a cytokine (small protein) released during the inflammatory response and several other proteins involved with inflammation, such as MCP-1 and C-Reactive protein have been repeatedly shown to cause insulin resistance.
• Inflammation of the brain (specifically the hypothalamus) causes leptin resistance, which often precedes and accompanies insulin resistance and Type 2 diabetes. Leptin is a hormone that regulates appetite and metabolism this through its effect on the hypothalamus. When the hypothalamus becomes resistant to leptin, glucose and fat metabolisms are impaired and weight gain and insulin resistance result.
• When there is inflammation of the gut, there arises leptin and insulin resistance. This may occur via 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.

5. How  does Diabesity Cause Inflammation?

In the past, fat was considered an inactive tissue with no biological action. It wasn’t considered for much other than storing energy. It has now emerged that fat tissue is a metabolically active endocrine organ that secretes hormones and inflammatory cytokines such as IL-6 and TNF-α. This metabolic activity of fat is the key to understanding its role in diabesity.

6. Why would obesity cause inflammation?

The first theory is that obesity-induced inflammation is a protective mechanism that prevents the body from losing mobility or fitness. Fat storage is an anabolic process, which means it builds up the organs and tissues. Inflammation, on the other hand, is a catabolic process which breaks down organs and tissues. It’s possible that the activation of catabolism via inflammation is the body’s attempt to keep weight within acceptable bounds. Evidence that experimentally induced local inflammation in fat tissue improves insulin resistance and causes weight loss supports this theory.

The second theory is that, obesity-induced inflammation 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 past 40 years. The surplus of modern, processed foods that accompanies diabesity is also a relatively new phenomenon. It’s possible that the stresses of obesity are similar enough to the stresses of an infection that the body reacts to obesity in the same way it would to an infection: via inflammation. Supporting this theory is evidence that the same intracellular, inflammatory stress pathways are activated in both obesity and infection.

7. Tackling Inflammation in the control of diabesity

We can therefore conclude that 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.  

Reduction of inflammation is a major key in preventing and treating diabesity. Focusing exclusively on regulating blood sugar and fat hormones without addressing other potential causes of inflammation is bound to produce inferior results.