Inflammasomes: Cause or consequence of obesity‐associated comorbidities in humans

Abstract

Inflammasomes are multiprotein intracellular complexes composed of innate immune system receptors and sensors; they activate the inflammatory cascade in response to infectious microbes and/or molecules derived from host proteins. Because of cytokine secretion, inflammasomes can induce amplified systemic responses, its dysregulation can exacerbate symptoms in infectious diseases, and it has been related to the development of autoimmune diseases, inflammatory disorders, and even cancer. Obesity is associated with a chronic low‐grade inflammation, in which circulating proinflammatory cytokines are elevated. Some publications describe changes in inflammation markers as a consequence of obesity, but others suggest that chronic inflammation might cause obesity (e.g., C‐reactive protein): these assumptions reflect the difficulty of identifying the appropriate role of inflammation as cause or consequence of obesity and its related complications. Obesity is recognized as a clinical risk factor for developing cardiovascular diseases including atherosclerosis, metabolic syndrome, insulin resistance, and diabetes mellitus. Changes in the expression of inflammasomes are described in some of these obesity‐related complications, and moreover, its modulation might exert a beneficial effect in some cases. Despite some contradictory results, most publications suggest a promising clinical effect based on in vitro and in vivo experiments. In this review, we summarized recent publications about inflammasome dysregulation in humans and its relationship with obesity‐related comorbidities.

Mediterranean Diet, Vitamin D, and Hypercaloric, Hyperproteic Oral Supplements for Treating Sarcopenia in Patients with Heart Failure—A Randomized Clinical Trial

“…Specifically, slow-release carbohydrates are associated with lower postprandial glycaemia due to slower glucose release, lower postprandial insulin release, and stimulation of gut hormones [ 31 ]. In HF, a significant glucose peak after the meal intake should be avoided, since hyperglycemia is associated with disordered endothelial function, increased low-grade inflammation, increased blood coagulation, reduced fibrinolysis, decreased plaque stability, reduced triglyceride-rich lipoprotein and LDL removal, increased HDL cholesterol catabolism, reductions in free fatty acids, reduced early-phase insulin secretion, and increased insulin resistance, which are related to worse clinical outcomes [ 32 , 33 ].…”

Adrenal incidentalomas, cortisol secretion and cancer: is there a real crosstalk?

“…Obesity is also strongly associated with an increased risk of different cancer types including endometrial, colorectal and breast cancer ( 29 ), but remarkably, it was not increased in patients with breast cancer and cortisol secretion. Interestingly, its prevalence was similar in the whole cohort and all cancer subtypes (but breast cancer), suggesting the relevance of obesity on inflammation and tumorigenesis ( 14 ).…”

“…Hyperinsulinism can also increase the production of reactive oxygen species (ROS), which can produce DNA damage and increase the risk of mutagenesis and carcinogenesis ( 16 ). Finally, adipocytes can release several interleukins that promote systemic inflammation which can result in a favorable environment for tumor growth ( 14 ). Other publications suggest an additional mechanism that links MACS and cancer, which is closely related to stress levels; specifically, several studies have reported that chronic exposure to physiological stress also increases cancer risk ( 17 ).…”

Body composition and sexual hormones for the glucose control of autoimmune diabetes in males: are they necessary to predict diabetes-related complications?

“…The evaluation of fat and lean mass is gaining a significant place in the regular evaluation of patients in different scenarios, since sarcopenia (lean mass loss) and fat mass (especially visceral fat) have been associated with increased inflammation, worse clinical outcomes and mortality in patient suffering from different diseases ( 32 – 36 ). Specifically, adipose tissue evaluated by BIVA and ultrasound has been associated with lower glucose variability and increased TIR, probably related with increased insulin resistance as previously reported in patients with T2DM ( 32 , 37 ). Furthermore, as in patients with obesity ( 32 ), adipose tissue and inflammation were correlated, despite C-RP were not above the reference range in the included patients.…”