Ciencias Exactas y Ciencias de la Salud

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Identification and Association of Fatty Acid Profile and Inflammation in Pediatric Type 2 Diabetes Mellitus and Metabolic Syndrome
(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2020) Navarro Guerra, Mariana; ELIZONDO MONTEMAYOR, LUZ LETICIA; 253956; CARVAJAL AGUILERA, KARLA GUADALUPE; 20316; GONZALEZ CASTILLO, ELENA CRISTINA; 167407; HERNANDEZ BRENES, CARMEN; 26334; Elizondo Montemayor, Luz Leticia; RR; García Rivas, Gerardo Jesús; Carvajal Aguilera, Karla Guadalupe; González Castillo, Elena Cristina; School of Medicine and Health Sciences; Campus Monterrey; Hernández Brenes, Carmen
Plasma fatty acid composition reflects dietary intake, as well as endogenous metabolism of fatty acids, which may be impaired in metabolic diseases. In adults, analysis of plasma fatty acids and their metabolism have been used to characterize their role in inflammation and obesity-related diseases such as Type 2 Diabetes Mellitus (T2DM), however evidence in the pediatric population is scarce. To the best of knowledge, there are no studies in T2DM pediatric patients focused on the quantification of fatty acid profiles and their potential relationship with inflammation markers. The objective of this study was to determine the association between the plasma fatty acid composition and inflammatory markers in pediatric Mexican patients with T2DM, Metabolic syndrome (MetS) and healthy controls (HC). Anthropometric and biochemical parameters were determined. Plasma fatty acid profiles were quantified by gas chromatography and plasma cytokines by flow-cytometry. Univariate and multivariate statistical analyses were conducted to establish differences and relationships between response variables investigated in the clinical groups. Patients with T2DM and MetS had distinct fatty acid profiles despite similarities between anthropometric and metabolic parameters. Higher proportions of C8:0 and n-6 polyunsaturated fatty acids (PUFA), lower n-3 PUFA and estimated delta-5-desaturase (D5D) activity could place MetS patients at higher risk of developing T2DM and cardiovascular disease. Despite having higher proportions of anti-inflammatory n-3 PUFAs, patients with T2DM had a pro-inflammatory profile characterized by higher proportions of C16:0 and elevated chemokines MCP-1, IL-8 and IL-18 concentrations. Higher percent contributions of odd chain saturated fatty acid (OCSFA) C17:0 were observed in plasma of patients with MetS and T2DM; its metabolic significance requires further research but a possible protective role in the reduction of inflammation seems to be supported by prior literature. Plasma monounsaturated fatty acids (MUFA) 18:1 n-9 and 16:1 n-7 appear to have a dual role in inflammation depending on the obese state. Characterization of the fatty acid profiles of a pediatric population with MetS and T2DM generated new knowledge of specific compounds such as C8:0 and C17:0, which may play a role in progression of obesity induced IR and inflammation to T2DM.
The role of irisin on the polarization of monocyte-derived macrophages from pediatric patients with type 2 diabetes mellitus
(Instituto Tecnológico y de Estudios Superiores de Monterrey) González Gil, Adrián Marcelo; Elizondo Montemayor, Luz Leticia; puelquio; García Rivas, Gerardo de Jesús; Estrada, Manuel; Genevieve Brunck, Marion Emilie; School of Medicine and Health Sciences; Campus Monterrey; González Castillo, Elena Cristina
Irisin is a novel peptide hormone released from skeletal muscle following acute bouts of physical exercise. Besides its originally described role on adipose tissue browning, its direct antiinflammatory properties have been recently described. Specifically, when murine RAW264.7 macrophages were pre-treated with irisin, both gene and protein expression of key proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6, decrease following exposure to lipopolysaccharide (LPS), while levels of the anti-inflammatory cytokine IL-10 increase. These changes have been linked to decreased TLR4 protein expression and activity of NF-ΚB. As well, in murine models, irisin has been described to favor an alternatively activated M2 macrophage phenotype, both from a M0 unstimulated state and a M1 classical proinflammatory state. Recently, the importance of an anti-inflammatory microenvironment to maintain the differentiation and function of brown adipose tissue has been emphasized in preclinical models, which could imply that irisin exerts its global metabolic effects indirectly through its action on adipose tissue macrophages, at least partially. Thus, irisin and its downstream pathways could represent a novel therapeutic target in type 2 diabetes mellitus (T2DM), a disease state characterized by a systemic low-grade proinflammatory state and lower circulating levels of irisin compared with healthy controls. In humans, evidence shows that M1 macrophage infiltrates in adipose tissue originate from circulating monocytes, but no studies have described the role of irisin on any type of human immune cell. Using monocyte-derived macrophages (MDMs) obtained from peripheral blood mononuclear cells (PBMCs) from a previously characterized cross-sample of pediatric T2DM patients (n=15) and matched healthy controls (n=8), we sought to determine differences in MDM immunophenotypes between groups, their response to in vitro treatment with recombinant human irisin, and to correlate patients’ basal monocyte subsets with their clinical and biochemical parameters and MDM phenotypes. In order to standardize the procedures previous to testing cryopreserved samples of T2DM and control pediatric patients, blood was obtained from one healthy adult individual. In this subject, in vitro irisin treatment significantly increased CD163 MFI. T2DM subjects had higher proportions of circulating intermediate monocytes (IMs) relative to healthy controls, which correlated positively with body fat percentage and the inflammatory marker hs-CRP and negatively with HDL-c. MDMs from T2DM subjects had similar polarization profiles compared with controls when exposed to IL-4 and IFN-γ and LPS. However, macrophage polarization capacity, as measured by M1 (CD80) and M2 (CD163, CD200R) marker MFI, was significantly associated with basal monocyte proportions when considering all participants. Upon irisin treatment, CD163 upregulation was no longer observed in MDMs from patient samples, but a trend towards decreased NF-κB activation was noted. Our results provide preliminary evidence in favor of irisin’s anti-inflammatory role in human macrophages but must be replicated in future studies with larger sample sizes. On the other hand, increased IMs in pediatric T2DM might suggest enhanced monocyte migration and differentiation to macrophages in obese white adipose tissue or to vascular atherosclerotic lesions early in disease evolution, which warrants future longitudinal and mechanistic studies.

Ciencias Exactas y Ciencias de la Salud

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