Chronic tissue inflammation and metabolic disease

Lee, Yun Sok; Olefsky, Jerrold M.

doi:10.1101/gad.346312.120

Cited by 179 publications

(118 citation statements)

References 260 publications

(335 reference statements)

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“…The innate immune system is largely responsible for this subclinical state of inflammation. In the adipose tissue of obese subjects, fatty acids may activate toll-like receptors (TLRs) present on adipocytes, triggering the production of inflammatory mediators and promoting the infiltration of inflammatory macrophages, thus enhancing the chronic state of low-grade inflammation [56,57].…”

Section: Obesity-associated Inflammatory Diseasesmentioning

confidence: 99%

Multifaceted Roles of CD5L in Infectious and Sterile Inflammation

Sanchez‐Moral

Ràfols

Martori

et al. 2021

IJMS

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CD5L, a protein expressed and secreted mainly by macrophages, is emerging as a critical immune effector. In addition to its well-defined function as an anti-apoptotic protein, research over the last decade has uncovered additional roles that range from pattern recognition to autophagy, cell polarization, and the regulation of lipid metabolism. By modulating all these processes, CD5L plays a key role in highly prevalent diseases that develop by either acute or chronic inflammation, including several infectious, metabolic, and autoimmune conditions. In this review, we summarize the current knowledge of CD5L and focus on the relevance of this protein during infection- and sterile-driven inflammatory pathogenesis, highlighting its divergent roles in the modulation of inflammation.

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Section: Obesity-associated Inflammatory Diseasesmentioning

confidence: 99%

Multifaceted Roles of CD5L in Infectious and Sterile Inflammation

Sanchez‐Moral

Ràfols

Martori

et al. 2021

IJMS

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“…Obesity is associated with an increased risk of metabolic syndrome and CVE within most westernized populations, but it also seems that fat distribution, lean mass, and cardio fitness, i.e., adiposity and cachexia, could play an essential role in determining morbidity. Abundant data indicate the presence of increased pro-inflammatory adipose tissue macrophages, as well as other immune cells, and decreased number, or proportion, of adipose tissue Treg cells, in obesity [ 39 ], which, in turn, could cause inflammation and contributes critically to atherothrombosis. Innate immunity may play an additional role in modulating metabolic and pro-inflammatory consequences in obesity, i.e., immunometabolism.…”

Section: Discussionmentioning

confidence: 99%

Higher levels of anti-phosphorylcholine autoantibodies in early rheumatoid arthritis indicate lower risk of incident cardiovascular events

et al. 2021

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Background The increased risk of cardiovascular events (CVE) in rheumatoid arthritis (RA) is not fully explained by traditional risk factors. Immuno-inflammatory mechanisms and autoantibodies could be involved in the pathogenesis of atherosclerotic disease. It has been suggested that anti-phosphorylcholine antibodies (anti-PC) of the IgM subclass may have atheroprotective effects. Here, we aimed to investigate the association between levels of IgM anti-PC antibodies with CVE in patients with early RA. Methods The study population was derived from the BARFOT early RA cohort, recruited in 1994–1999. The outcome of incident CVE (AMI, angina pectoris, coronary intervention, ischemic stroke, TIA) was tracked through the Swedish Hospital Discharge and the National Cause of Death Registries. Sera collected at inclusion and the 2-year visit were analyzed with ELISA to determine levels of anti-PC IgM. The Kaplan-Meier estimates and Cox proportional hazards regression models were used to compare CV outcome in the groups categorized by baseline median level of IgM anti-PC. Results In all, 653 patients with early RA, 68% women, mean (SD) age 54.8 (14.7) years, DAS28 5.2 (1.3), 68% seropositive, and without prevalent CVD, were included. During the follow-up of mean 11.7 years, 141 incident CVE were recorded. Baseline IgM anti-PC above median was associated with a reduction in risk of incident CVE in patients aged below 55 years at inclusion, HR 0.360 (95% CI, 0.142–0.916); in males, HR 0.558 (0.325–0.958); in patients with BMI above 30 kg/m2, HR 0.235 (0.065–0.842); and in those who did not achieve DAS28 remission at 1 year, HR 0.592 (0.379–0.924). The pattern of associations was confirmed in the models with AUC IgM anti-PC over 2 years. Conclusion Protective effects of higher levels of innate IgM anti-PC autoantibodies on CVE were detected in younger patients with RA and those at high risk of CVE: males, presence of obesity, and non-remission at 1 year.

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“…Increased adipose tissue mass is a hallmark of obesity and is present in the great majority of individuals with type 2 diabetes mellitus (T2DM) (Kusminski et al, 2016;Ghaben and Scherer, 2019). In obesity, both in the presence and absence of diabetes, chronic tissue inflammation, particularly in adipose tissue and liver, is an important contributor to insulin resistance (Hotamisligil and Erbay, 2008;Lackey and Olefsky, 2016;Lee and Olefsky, 2021;Saltiel, 2021;Ferrante, 2013). Obesityinduced chronic inflammation is not confined to adipose and liver since there are reports of proinflammatory pathway activation in the CNS, the gastrointestinal tract, muscle, and pancreatic islets, consistent with an intra-and interorgan network of crosstalk in these complex heterogeneous disorders (Lee and Olefsky, 2021).…”

Section: Adipose Tissue Exosome Biologymentioning

confidence: 99%