Infections and immunity: associations with obesity and related metabolic disorders

Abstract

About one-fourth of the global population is either overweight or obese, both of which increase the risk of insulin resistance, cardiovascular diseases, and infections. In obesity, both immune cells and adipocytes produce an excess of pro-inflammatory cytokines that may play a significant role in disease progression. In the recent coronavirus disease 2019 (COVID-19) pandemic, important pathological characteristics such as involvement of the renin-angiotensin-aldosterone system, endothelial injury, and pro-inflammatory cytokine release have been shown to be connected with obesity and associated sequelae such as insulin resistance/type 2 diabetes and hypertension. This pathological connection may explain the severity of COVID-19 in patients with metabolic disorders. Many studies have also reported an association between type 2 diabetes and persistent viral infections. Similarly, diabetes favors the growth of various microorganisms including protozoal pathogens as well as opportunistic bacteria and fungi. Furthermore, diabetes is a risk factor for a number of prion-like diseases. There is also an interesting relationship between helminths and type 2 diabetes; helminthiasis may reduce the pro-inflammatory state, but is also associated with type 2 diabetes or even neoplastic processes. Several studies have also documented altered circulating levels of neutrophils, lymphocytes, and monocytes in obesity, which likely modifies vaccine effectiveness. Timely monitoring of inflammatory markers (e.g., C-reactive protein) and energy homeostasis markers (e.g., leptin) could be helpful in preventing many obesity-related diseases.

Signaling Modifications Associated with Obesity and Dysbiosis and Their Impact on Metabolic Disorders

“…In particular, leptin is associated with intracellular signaling pathways as well as inflammatory molecules, including IL-6, TNF-α, NO, eicosanoid and cyclooxygenase 2 [58,59]. Additionally, similar signaling pathways such as AMPK, JAK/STAT, and PI3K pathways are also involved in inflammation and immunity, therefore, in the pathogenesis of obesity and related metabolic disorders [60]. Notably AMPK signaling pathway plays an important role in the regulation of gut microbiota-mediated metabolism.…”

Dysbiosis of the gut microbiota and its effect on α-synuclein and prion protein misfolding: consequences for neurodegeneration

“…The gut microbiome has been implicated in neuroinflammation, which is a prominent feature of prion diseases (D'Argenio and Sarnataro, 2019; Zhu et al, 2020;Trichka and Zou, 2021). The postulated conjecture posits that prion agents ingested through dietary intake may instigate perturbations in the gut microbiota, leading to dysbiosis (D'Argenio and Sarnataro, 2019; Andrea et al, 2023;Ray et al, 2023). Subsequently, this dysbiotic state may elicit the generation of a microbial form of amyloid, eliciting an immune response that amplifies microglial and astrocytic activation in the brain.…”

Obesity and consequent changes in the body

“…Takođe, CRP učestvuje u brojnim fiziološkim i patofiziološkim procesima, kao što su: aktivacija sistema komplementa, fagocitoza, apoptoza, oslobađanje azot oksida (NO), biosinteza raznih citokina, posebno proinflamatornih citokina (TNF-, MCP-1, IL-6). Osim toga veruje se da CRP stimuliše proces hemotakse i usmeravanja (regrutacije) cirkulišućih belih krvnih ćelija ka mestu zapaljenja (56).…”