Immunology of chronic low-grade inflammation: relationship with metabolic function

Abstract

Inflammation is part of the body’s innate immune response and is an essential process that not only defends against harmful bacteria and pathogens but also plays a key role in the maintenance and repair of tissues. Under pathological conditions, there is bilateral crosstalk between immune regulation and aberrant metabolism resulting in persistent inflammation in the absence of infection. This phenomenon is referred to as sterile metabolic inflammation (metainflammation) and occurs if the initiating stimulus is not removed or if the resolution process is disrupted. Disruption of this tightly regulated immune response and its failure to resolve as is evident in metabolic disorders and is not only associated with disease progression but also leads to immune senescence and should not be neglected in the clinical management of patients. This review gives an overview of the mechanisms underlying chronic metabolic inflammation, the aberrant metabolic activation of innate immune cells (neutrophils, macrophages, mast cells, dendritic cells) and its role in disease progression using obesity-diabetes as a prime example. Addressing the underlying subclinical metabolic inflammation in addition to achieving glucose control may contribute significantly towards therapeutic interventions aimed at preventing the onset of co-morbidities in diabetic patients.

Adherence to Lifestyle Recommendations Linked to Innate Immunity and Lipoprotein Metabolism: A Cross-Sectional Comparison Using Untargeted Proteomics

“…The elevation of proteins in CON indicates a systemic innate immune system activation consistent with higher serum CRP and metabolic in ammation (27)(28)(29)(30)(31). Serum amyloid P (APCS), for example, is a pentraxin and an acute phase protein that along with CRP promotes phagocytosis via complementdependent pathways (32).…”

Serum uric acid to high‐density lipoprotein ratio as a novel indicator of inflammation is correlated with the presence and severity of metabolic syndrome: A large‐scale study

“…MetS is a tremendously growing public health problem, which is comprised of interconnected and heterogeneous metabolic origin risk factors that appear to be directly promoting the development of type 2 DM, adverse cardiovascular events and all‐cause mortality 24 . MetS induces low‐grade chronic systemic inflammation in the circulation and peripheral metabolic tissues, defined as ‘metabolic inflammation’, which is different from classical inflammation 25,26 . Numerous studies confirmed that CRP as a conventional marker of systemic inflammation is correlated with the number of MetS components (i.e.…”

“… 24 MetS induces low‐grade chronic systemic inflammation in the circulation and peripheral metabolic tissues, defined as ‘metabolic inflammation’, which is different from classical inflammation. 25 , 26 Numerous studies confirmed that CRP as a conventional marker of systemic inflammation is correlated with the number of MetS components (i.e. MetS severity) and a higher CRP level was associated with an increased incidence of cardiovascular events.…”

Prohibitions in the meta-inflammatory response: a review

“…Pathological alterations in cell metabolism and abnormal activation of innate immunity associated with excess fatty acids, their transport, accumulation of lipid droplets and disruption of interorganelle connections lead to reprogramming of nuclear DNA: expression of certain transcription factors and genes that activate the processes of cell aging, cell death and maintenance of the inflammatory response. The link between sterile metabolic inflammation in obesity and aging processes at the cellular and organismal level is emphasized ( Lee, 2022 ; van de Vyver, 2023 ). An increase in the number of senescent cells, which differ in genotype and produce a secretory pro-inflammatory phenotype/senescence-associated phenotype (SASP), inhibit adipogenesis and induce the development of insulin resistance (IR) ( Palmer et al, 2019 ).…”