How Does Inflammation Affect Metabolic Health?

How Does Inflammation Affect Metabolic Health?

What Is Inflammation?  

Inflammation, as we typically define it, is the body’s immune response to harmful stimuli such as toxins, pathogens, radiation, and damaged cells.1–3 When the body recognizes a foreign substance, it releases inflammatory mediators to remove harmful stimuli through various actions such as recruiting white blood cells. An acute inflammation can also become a chronic inflammation when uncontrolled or when continually exposed to toxins. Chronic inflammation can become a large stressor and is known to be associated with chronic inflammatory diseases and chronic conditions such as diabetes, cardiovascular disease, and cancer. Inflammation as it relates to metabolic health falls more under the category of chronic inflammation, or more specifically as metabolically triggered inflammation.

 

Inflammation & Obesity  

Obesity is a chronic disease that affects a wide array of diseases and is known as a state of low-grade chronic inflammation.4 Recent decades of research clearly suggests that obesity is associated with chronic inflammation, along with a host of other metabolic and chronic conditions.3,5 Studies have demonstrated that adipose (ie, fat) tissues are not only fat-storing organs but are endocrine (ie, hormonal) in nature.4 These tissues are metabolically active and can also become inflamed, releasing various inflammatory markers.4,5 Elevated inflammatory markers have consistently been observed in adipose tissues in both obese humans and animals. It is thought that obesity induces apoptosis (ie, cell death) and inflammation within adipose tissue, which subsequently triggers further inflammation that can have negative consequences on the body’s metabolic functions. Although the exact relationship between inflammation and obesity is still be studied, it is thought that expanding adipocytes, or adipose cells, may release signals that trigger inflammation in an effort to clear or limit expansion of adipocytes.

 

Inflammation & Diabetes

Studies are showing that obesity-linked inflammation may elucidate the relationship between obesity and insulin resistance and type 2 diabetes mellitus. Studies have shown that inflammation contributes to the development of insulin resistance, although insulin resistance may sometimes precede inflammation in the adipose tissue.5 It is thought that adipose tissues release hormones and other factors that influence insulin signaling as well as insulin sensitivity of tissues such as skeletal muscle and liver. For instance, a specific inflammatory marker called tumor necrosis factor-a is a proinflammatory cytokine (ie, a type of protein that promotes inflammation) and is shown to be particularly elevated in obesity. This factor has been shown to inhibit insulin action and play a role in the development of insulin resistance. On the other hand, reduction of inflammation has been associated with improved metabolic functions and insulin resistance in obese animal models.

 

Inflammation & Heart Health

Scientists are beginning to view inflammation as a cardiovascular (ie, heart and blood-vessel related) risk factor, with studies finding that elevated levels of inflammatory markers are associated with an increased risk of a cardiovascular event (eg, heart attack) even when cholesterol levels are controlled.6 Chronic inflammatory conditions such as rheumatoid arthritis (ie, autoimmune condition of joints) and systemic lupus erythematosus (ie, whole-body autoimmune disorder) are also associated with increased risk of cardiovascular disease (CVD) risk. The underlying pathology of CVD is known to be atherosclerotic in nature, which describes the hardening of the arteries from build-up of cholesterol plaques.1 With recent research showing that inflammation plays a key role in all processes of atherosclerosis, from the formation of atherosclerotic plaque to the rupture of the plaque, atherosclerosis is being redefined as a chronic inflammatory condition.7 Inflammatory cells are shown to penetrate into plaques and can release factors that influence how the plaque forms, grows, and ruptures. Recent findings on the role of inflammation have led to new therapies that target inflammation to treat CVD as well as other metabolic diseases.5,7

 

References:
1. Chen L, Deng H, Cui H, et al. Inflammatory Responses and Inflammation-Associated Diseases in Organs. Oncotarget. 2017;9(6):7204-7218. doi:10.18632/oncotarget.23208
2. Stone WL, Basit H, Burns B. Pathology, Inflammation. In: StatPearls. StatPearls Publishing; 2023. Accessed August 29, 2023. http://www.ncbi.nlm.nih.gov/books/NBK534820/
3. Hotamisligil GS. Inflammation and Metabolic Disorders. Nature. 2006;444(7121):860-867. doi:10.1038/nature05485
4. Hildebrandt X, Ibrahim M, Peltzer N. Cell Death and Inflammation During Obesity: “Know My Methods, Wat(son).” Cell Death Differ. 2023;30(2):279-292. doi:10.1038/s41418-022-01062-4
5. Wu H, Ballantyne CM. Metabolic Inflammation and Insulin Resistance in Obesity. Circulation Research. 2020;126(11):1549-1564. doi:10.1161/CIRCRESAHA.119.315896
6. Alfaddagh A, Martin SS, Leucker TM, et al. Inflammation and Cardiovascular Disease: From Mechanisms to Therapeutics. Am J Prev Cardiol. 2020;4:100130. doi:10.1016/j.ajpc.2020.100130
7. Henein MY, Vancheri S, Longo G, Vancheri F. The Role of Inflammation in Cardiovascular Disease. Int J Mol Sci. 2022;23(21):12906. doi:10.3390/ijms232112906

 

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