Inflammation & Metabolism
What Is Immunometabolism?
The immune system and metabolism were once studied largely as separate subjects. Researchers now know that they are closely connected. This growing field is known as immunometabolism.
Immune cells need energy to function, and the fuels they use can change when they become activated. Some activated immune cells increase their use of glucose, even when oxygen is available—a metabolic shift resembling the Warburg effect seen in cancer cells. Other immune cells rely more heavily on fatty acids and mitochondrial energy production.
These metabolic changes can actually help determine how immune cells behave, including whether they promote or suppress inflammation. At the same time, metabolic problems such as insulin resistance, obesity, and chronically elevated blood glucose can affect inflammatory pathways.
This raises an intriguing question: could improving metabolic health also influence inflammation and autoimmune disease? The science is developing rapidly, but the answer is not yet clear for most autoimmune diseases.
Insulin Resistance & Inflammation
Insulin resistance and chronic inflammation are closely connected. When cells become less responsive to insulin, the body often produces more insulin to keep blood glucose under control. Insulin resistance frequently occurs together with abdominal obesity, elevated blood sugar, and other features of metabolic syndrome.
Excess body fat—particularly visceral fat around the abdominal organs—can release inflammatory signaling molecules. At the same time, chronic inflammation can interfere with insulin signaling, creating a cycle in which metabolic dysfunction and inflammation reinforce each other.
This relationship is well established in metabolic diseases such as type 2 diabetes and cardiovascular disease. Researchers are investigating how much it may also influence autoimmune diseases and whether improving insulin sensitivity can reduce inflammation or disease activity.
Ketones & Inflammation
Ketones are molecules produced by the liver when carbohydrate availability is low, such as during fasting or a very low-carb diet. They can serve as an alternative fuel for the brain and other tissues, but researchers have discovered that ketones may also act as signaling molecules.
One ketone, beta-hydroxybutyrate (BHB), has been shown in laboratory, human-cell, and animal research to influence inflammatory pathways. A landmark study found that BHB inhibited the NLRP3 inflammasome, an important part of the body's inflammatory response.
This has raised interest in whether fasting, ketogenic diets, or other approaches that increase ketones might help reduce inflammation. More recent research continues to explore ketones as potential regulators of immune function.
But there is an important distinction between demonstrating a biological mechanism and showing that it improves disease in people. Evidence that nutritional ketosis can treat autoimmune disease remains limited.
The biological mechanism is intriguing and worth studying, but clinical benefits need to be demonstrated disease by disease.
Can Improving Metabolic Health Help?
Improving metabolic health can reduce several factors associated with chronic inflammation. Weight loss when needed, exercise, better blood-glucose control, improved insulin sensitivity, adequate sleep, and a nutrient-dense diet can all influence metabolic and inflammatory pathways.
For people with obesity or insulin resistance, these changes may be particularly important. Research suggests that metabolic health and immune function interact in numerous ways.
Whether improving metabolic health directly changes the underlying autoimmune process is much less certain. The effects are likely to differ among diseases and among individuals.
Still, metabolic health is important for overall health regardless of its effect on autoimmunity. If better metabolic health also helps regulate inflammation or immune function, that could provide an additional benefit.
Key Takeaways
Metabolism and immune function are closely connected. The fuels immune cells use can influence how they behave.
Insulin Resistance and chronic inflammation can reinforce each other, particularly in people with metabolic dysfunction.
Ketones such as beta-hydroxybutyrate can influence inflammatory pathways, although their clinical importance in autoimmune disease is still being studied.
Improving metabolic health through diet, exercise, weight management, sleep, and better glucose control can reduce several contributors to chronic inflammation.
Immunometabolism is a promising field, but treatments based specifically on changing immune-cell metabolism are still developing.
The effects of metabolic interventions on autoimmune disease need to be evaluated disease by disease rather than assumed to apply to all autoimmune conditions.
Learn More
A major review in Nature Reviews Immunology explaining how immune cells change their use of glucose, fats, and other fuels when activated—and how these metabolic changes can influence immune function.
A review examining how altered metabolism in immune cells may contribute to autoimmune diseases including rheumatoid arthritis, lupus, multiple sclerosis, and diabetes, and whether metabolic pathways could eventually become treatment targets.
A review examining how metabolic pathways within immune cells regulate inflammation and how some existing anti-inflammatory medications may work partly by affecting these pathways.
A landmark 2015 study found that beta-hydroxybutyrate (BHB) inhibited the NLRP3 inflammasome, an important inflammatory pathway. The research included human immune cells and animal models, but it does not establish that ketogenic diets treat autoimmune disease in people.