Chronic Low-grade Inflammation Of Adipose Tissue Research Articles

Macrophage-associated markers of metaflammation are linked to metabolic dysfunction in pediatric obesity

BackgpoundMetabolically driven chronic low-grade adipose tissue inflammation, so-called metaflammation, is a central feature in obesity. This inflammatory tone is largely driven by adipose tissue macrophages (ATM), which express pro- and anti-inflammatory markers and cytokines such as, e.g., IL-1 receptor antagonist (IL-1RA), CD163 and osteopontin (OPN). Metaflammation ultimately leads to the development of cardiometabolic diseases. This study aimed to evaluate the association between selected adipose tissue macrophage-associated markers and metabolic comorbidities in pediatric obesity. MethodsFrom a pediatric cohort with obesity (n = 108), clinically thoroughly characterized including diverse routine blood parameters, oral glucose tolerance test and liver MRI, plasma IL-1RA, soluble (s)CD163 and OPN were measured by ELISA. ResultsWe observed significantly higher IL-1RA, sCD163, and OPN levels in the plasma of children with metabolic-dysfunction associated fatty liver disease (MAFLD) and metabolic syndrome. Moreover, IL-1RA and sCD163 correlated with hepatic disease and apoptosis markers alanine aminotransferase and CK-18. IL-1RA concentrations additionally correlated with insulin resistance, while children with disturbed glucose metabolism had significantly higher levels of sCD163. ConclusionMAFLD and other metabolic disorders in pediatric patients with obesity are associated with an elevation of adipose tissue macrophage-related inflammation markers.

꾸지뽕 열매 발효식초의 3T3-L1 세포에서 항염증 및 인슐린 저항성 개선 효과

Obesity is associated with chronic low-grade adipose tissue inflammation, leading to insulin resistance. Inflammation associated with insulin resistance is an interesting area of biomedical research and is expected to affect insulin signaling pathways via the downregulation of glucose transporters. In the present study, we investigated the inhibitory effects of Maclura tricuspidata fruit vinegar (MFV) against TNF-α-induced inflammation and insulin resistance in 3T3-L1 adipocytes. Differentiated 3T3-L1 adipocytes were pretreated with MFV at various concentrations and then cultured with TNF-α to induce insulin resistance. Then, lipid droplets, inflammatory cytokine and glucose uptake, PPARγ and GLUT4 expression, and IRS-1 phosphorylation were analyzed. MFV attenuated the TNF-α-induced decrease in lipid droplets and glucose uptake and inhibited TNF-α-induced inflammatory cytokine, IL-6, and MCP-1 production. MFV reversed the decrease in adiponectin produced by TNF-α. Furthermore, MFV upregulated the TNF-α-induced suppression of PPARγ and GLUT4 protein expression and reduced the TNF-α-induced phosphorylation of IRS-1. These findings suggest that MFV effectively ameliorates TNF-α-induced insulin resistance; accordingly, we recommend the use of MFV for the control and management of insulin resistance and its associated complications.

Pro-inflammatory effects of DEHP in SGBS-derived adipocytes and THP-1 macrophages

In the member countries of the Organization for Economic Co-operation and Development (OECD), overweight and obesity affect the majority of the population. The use of environmental chemicals, such as the plasticizer DEHP, has largely increased simultaneously with this development. DEHP is an "obesogen" that interferes with normal adipocyte differentiation and energy homeostasis. Obesity in turn is accompanied by chronic low-grade adipose tissue inflammation, leading to metabolic disorders such as type II diabetes. The main actors in adipose tissue inflammation are adipocytes and macrophages. However, the impact of DEHP on adipose tissue inflammation and the crosstalk between adipocytes and macrophages are unknown and the subjects of the current study. The influence of DEHP on inflammation was investigated in human Simpson–Golabi–Behmel syndrome (SGBS)-derived adipocytes and human THP-1 macrophages. The proinflammatory markers IL8, MCP1, IL1β, TNFα and others were measured (qRT-PCR, ELISA) in SGBS-derived adipocytes treated with DEHP [day 0 (d0)–d4; 50 µg/ml] and THP-1 macrophages cultured with conditioned medium (CM) from DEHP-treated adipocytes (SGBS-CM) (from d4 and d8). DEHP exposure led to a proinflammatory state in SGBS-derived adipocytes (e.g., increased secretion of IL8 and MCP1). Surprisingly, exposure of THP-1 macrophages to SGBS-CM did not show DEHP-induced effects. However, we demonstrated that medium containing (pre)adipocyte-secreted factors had a significant impact on the expression and secretion of macrophage and inflammatory markers in THP-1 macrophages in general and led to the significantly increased accumulation of intracellular lipid droplets.

Association of a variant in the gene encoding for ERV1/ChemR23 with reduced inflammation in visceral adipose tissue from morbidly obese individuals

Obesity comorbidities are closely associated with chronic low-grade adipose tissue inflammation. A number of SNPs associated with inflammation has been identified, underscoring the impact of genetic determinants on this process. Here, we screened SNPs in genes with pro-inflammatory (IL-1β, IL-6, STAT3 and JAK2), anti-inflammatory (IL-10 and SOCS3) and pro-resolving (ERV1/ChemR23) properties in 101 obese and 99 non-obese individuals. Among the SNPs analyzed, we identified that individuals carrying a C allele in the rs1878022 polymorphism of the ERV1/ChemR23 gene, which encodes for the receptor of the pro-resolving mediator RvE1, had increased ERV1/ChemR23 protein expression and reduced levels of the inflammatory cytokine IL-6 in adipose tissue. Moreover, patients carrying the C allele in homozygosity had lower plasma levels of IL-6, IFN-α2, IL-15, IL-1ra, IL-10, GM-CSF, G-CSF and VEGF and enhanced leukocyte responsiveness to RvE1. C-carriers also exhibited decreased TAG to HDL ratio, a surrogate marker of insulin resistance and a predictor of incident fatty liver. Finally, we confirmed in vivo that the ERV1/ChemR23 receptor regulates systemic and tissue inflammation since mice lacking ERV1/ChemR23 expression showed increased IL-6 levels in adipose tissue and peritoneal macrophages. Together, our study identified an ERV1/ChemR23 variant that protects patients with obesity from excessive inflammatory burden.

The role of omega-3 fatty acid receptor GPR120 in insulin resistance

Obesity is the dominant cause of acquired insulin resistance, and it is the epidemic of obesity in the United States that is driving the markedly increasing incidence of type 2 diabetes. Adipocyte dysfunction and chronic low-grade adipose tissue (AT) inflammation are the major causes of insulin resistance. Abnormal accumulation and activation of AT macrophages (ATMs) and abnormal activation of the TLR4-mediated immune responses within ATMs are the key characters of the chronic low-grade AT inflammation associated with insulin resistance. We have recently shown that GPR120 acts as a physiological receptor of omega-3 fatty acid in macrophages and adipocytes, which mediate potent anti-inflammatory and insulin-sensitizing effects. The important role that GPR120 has in the control of inflammation raises the possibility that targeting this receptor could have therapeutic potential in many inflammatory diseases including obesity and type 2 diabetes. In this review paper, we discuss omega-3 fatty acid-sensing GPR120 and highlight the potential outcomes of targeting this receptor in ameliorating disease.