Metabolic inflammation and obesity feed each other. Inflammation starts in the fat cells themselves and grows as fat mass expands. Cytokines such as TNF-α then cause insulin resistance. Inflammation in the hypothalamus causes leptin resistance, which drives more weight gain. The end point is diabesity: diabetes occurring in the context of obesity.
Obesity is a disease that has plagued modern man in recent times. Access to highly processed foods and less physical activity are key contributors to it. Researchers are hard at work on what other underlying factors lead to obesity. That matters because of its link to the onset of Type 2 Diabetes, Cardiovascular diseases, and liver disease. In this article we take an in-depth look at metabolic inflammation. We look at its role in the onset of obesity. Let’s dive in.
- What is obesity?
Obesity is marked by a low-grade chronic state of inflammation. In it, the levels of pro-inflammatory cytokines such as TNF-α, IL-6, and CRP are increased. In this state, too much subcutaneous and/or abdominal adipose tissue (fat under the skin and/or in the belly) builds up. This adipose tissue is no longer considered inert and mainly devoted to storing energy. It is emerging as an active tissue. It helps regulate physiological and pathological processes, including immunity and inflammation. Obesity is diagnosed when your body mass index (BMI) is 30 or higher. To find your body mass index, divide your weight in pounds by your height in inches squared. Then multiply by 703. Or divide your weight in kilograms by your height in meters squared.
| BMI | Weight status |
| Below 18.5 | Underweight |
| 18.5-24.9 | Normal |
| 25.0-29.9 | Overweight |
| 30.0 and higher | Obesity |
For most people, BMI gives a reasonable estimate of body fat. However, BMI doesn’t directly measure body fat. So some people, such as muscular athletes, may have a BMI in the obesity category even though they don’t have excess body fat.
- What is Diabesity?
‘Diabesity’ is the term for diabetes occurring in the context of obesity. This form of obesity-dependent diabetes has become a major public health problem in recent times. At its base, it is explained by insulin resistance and pancreatic beta-cell dysfunction. Still, new patterns have evolved to explain these changes in the context of the modern spates of obesity and diabetes.
- Is obesity an inflammatory condition?
The link between obesity and inflammation has often been debated in the recent past. Many people do not know that the link was made decades ago. Over a century ago, doctors used high doses of a class of anti-inflammatory compounds, including aspirin, called salicylates to treat Type 2 diabetes. In some cases, the symptoms of diabetes totally went away. Unfortunately, this treatment was stopped due to the serious side effects caused by the high doses of salicylates. Now we will look in depth at the questions of our topic today. Does obesity cause inflammation? Or is inflammation caused by something secondary to obesity (like high blood sugar or triglycerides)? How about diabesity? Does diabesity cause inflammation, or does inflammation cause diabesity? How and why does the body start an inflammatory response to diabesity? Let us tackle each item separately.
- How does Inflammation Cause Diabesity?
We look at some lines of evidence. They show that inflammation directly causes obesity and diabesity.
- Diabesity has been shown to develop after inflammation. Raised levels of inflammatory cytokines predict coming weight gain. In one study, infusing inflammatory cytokines into healthy, normal-weight mice caused insulin resistance. Another fact shows this too. People with other chronic inflammatory conditions are at higher risk of getting Type 2 Diabetes. For example, about one-third of chronic Hepatitis C patients develop T2DM. People 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. An explanation for this may be the dysfunction of the mitochondria (the “power plant” of our cells), caused by the added stress obesity puts on cell function. Another mechanism may be oxidative stress. As more glucose is delivered to the fat cells, they make an excess of reactive oxygen species (ROS). These in turn start an inflammatory cascade within the cell.
- Further, inflammation of the fat tissue causes insulin resistance, which is the primary feature of T2DM. TNF-α is a cytokine (small protein) released during the inflammatory response. It has been repeatedly shown to cause insulin resistance. Several other proteins involved with inflammation, such as MCP-1 and C-Reactive protein, have also been shown to cause insulin resistance.
- Also, inflammation of the brain (specifically the hypothalamus) causes leptin resistance. Leptin resistance often comes before and with insulin resistance and T2DM. 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 impaired. Weight gain and insulin resistance result.
- When there is inflammation of the gut, leptin and insulin resistance arise. This may occur via a rise in lipopolysaccharide (LPS). LPS is an endotoxin (a toxin from inside bacteria) made by Gram-negative bacteria in the gut. LPS has been shown to cause inflammation, insulin resistance in the liver and weight gain.
- 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. We now know that fat tissue is a metabolically active endocrine organ. It 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.
- Why would obesity cause inflammation?
The first theory is that obesity-induced inflammation is a protective mechanism. It keeps 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. Catabolism breaks down organs and tissues. It’s possible that turning on catabolism via inflammation is the body’s attempt to keep weight within acceptable bounds. Evidence supports this theory. In experiments, causing local inflammation in fat tissue improves insulin resistance and causes weight loss. The second theory is that obesity-induced inflammation is simply a malfunction. Human evolution never selected against it. Obesity and its related disorders have been extremely rare throughout human history. They have only become common in the past 40 years. The surplus of modern, processed foods that comes with diabesity is also a fairly new thing. It’s possible that the stresses of obesity are similar enough to the stresses of an infection. If so, the body reacts to obesity in the same way it would to an infection: via inflammation. Evidence supports this theory. The same intracellular, inflammatory stress pathways are turned on in both obesity and infection.
- 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 set in, each can further stimulate the production of inflammatory cytokines. This forms a vicious cycle of inflammation and diabesity. Reducing inflammation is a major key in preventing and treating diabesity. Focusing only on regulating blood sugar and fat hormones, without addressing other potential causes of inflammation, is bound to produce inferior results.
Related reading
References
1. NCBI (2003): Diabesity: an inflammatory metabolic condition. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/14598860 2. NCBI (2013): Obesity, Inflammation, and Diet. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819692/ 3. NCBI (2006): Inflammation and insulin resistance. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1483173/ 4. Chris Kresser (2019): How Inflammation Makes You Fat and Diabetic (And Vice Versa). Retrieved from https://chriskresser.com/how-inflammation-makes-you-fat-and-diabetic-and-vice-versa/
Medically reviewed by Dr. Gurpreet Singh Padda, MD, MBA, MHP
Interventional pain physician, addiction medicine specialist and obesity medicine diplomate.
Licensed in Missouri and Illinois.
Last reviewed June 18, 2026
