CCL2 Serum Levels and Adiposity Are Associated with the Polymorphic Phenotypes -2518A on CCL2 and 64ILE on CCR2 in a Mexican Population with Insulin Resistance

Abstract

Genetic susceptibility has been described in insulin resistance (IR). Chemokine (C-C motif) ligand-2 (CCL2) is overexpressed in white adipose tissue and is the ligand of C-C motif receptor-2 (CCR2). The CCL2 G-2518A polymorphism is known to regulate gene expression, whereas the physiological effects of the CCR2Val64Ile polymorphism are unknown. The aim of the study is to investigate the relationship between these polymorphisms with soluble CCL2 levels (sCCL2), metabolic markers, and adiposity. In a cross-sectional study we included 380 Mexican-Mestizo individuals, classified with IR according to Stern criteria. Polymorphism was identified using PCR-RFLP/sequence-specific primers. Anthropometrics and metabolic markers were measured by routine methods and adipokines and sCCL2 by ELISA. The CCL2 polymorphism was associated with IR (polymorphic A+ phenotype frequencies were 70.9%, 82.6%, in individuals with and without IR, resp.). Phenotype carriers CCL2 (A+) displayed lower body mass and fat indexes, insulin and HOMA-IR, and higher adiponectin levels. Individuals with IR presented higher sCCL2 compared to individuals without IR and was associated with CCR2 (Ile+) phenotype. The double-polymorphic phenotype carriers (A+/Ile+) exhibited higher sCCL2 than double-wild-type phenotype carriers (A−/Ile−). The present findings suggest that sCCL2 production possibly will be associated with the adiposity and polymorphic phenotypes of CCL2 and CCR2, in Mexican-Mestizos with IR.

Ageing influences the relationship of circulating miR-33a and miR-33b levels with insulin resistance and adiposity

“…26 In another context, we have previously reported frequencies of IR of 39% in individuals with excess of weight 2 and 62% in individuals with obesity in our population aged 20-59 years; 27 this cohort also included 31.3% of individuals with dyslipidemias. 28 These frequencies are in agreement with the group included for this study, and in which, risk factors for the development of IR were identified.…”

“…Our previous works also show similar lipid profile and no differences in HDLc levels in our population with IR versus without IR. 2,27,28 Amid of this fact, it was not possible to establish the clinical relationship between the circulating levels of the miR-33 family and HDLc.…”

Immunometabolism in Obesity

“…interferon (IFN)-γ) or by pathogen-associated molecular patterns (PAMPs) (i.e. LPS) and is characterized by the production of pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ, IL-1β, IL-12 and IL-23), chemokines promoting inflammatory infiltrate (CXCL9, 10,11,13,CCL8,15,19,20), and expressed on surface high levels of MHCII, CD80, CD86 and CD11c, among other markers (i.e. Ly6C, CD11b, CD62L, CCR2, CX3CR1 and CCR5).…”

Adipose tissue macrophage in immune regulation of metabolism

“…Metabolic diseases Reference IL-4 promoter polymorphism (IL-4 C-589T and C-34T) Type 2 diabetes (Ho et al, 2010) IL-4 promoter polymorphism (IL-4-589 C/C) Lower circulatory high-density lipoprotein cholesterol level (HDL-C) (Ho et al, 2010) IL-4Rα polymorphism (IL-4Rα E400A) Dysfunction of lipid metabolism (Chang et al, 2012) IL-4Rα haplotypes Type 1 diabetes (Mirel et al, 2002) IL-4Rα, IL-4 and IL-13 loci Type 1 diabetes (Bugawan et al, 2003) IL-4 locus Type 2 diabetes (Ban et al, 2010) IL-6 single nucleotide polymorphism (IL-6C-174G) Type 2 diabetes (Illig et al, 2005) CCL2 and CCR2 polymorphism (CCL2 G-2518A), CCR2 (Val64Ile) Insulin resistance (Guzman-Ornelas et al, 2016) SNPs and haplotypes in TLR1 and TLR6 Type 1 diabetes (Sun et al, 2014) TLR4 variants High TC/HDL-C (Kolz et al, 2008) ing in response to the cold challenge or hormonal stimulation (Hui et al, 2015;Qiu et al, 2014). In accordance, elevated production of meteorin-like protein (Metrnl) in adipose tissue upon cold exposure and in muscle after exercise training, was recently shown to exert beneficial effects upon energy expenditure, adipose inflammation, and glucose metabolism through inducing the production of eosinophil-derived IL-4, which could in turn promote the M2 activation of ATMs and browning of scWAT (Rao et al, 2014).…”