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.

Objective: The identification of circulating microRNAs related to abnormal metabolic function may be useful in the context of ageing, adiposity and insulin resistance. The miR-33a/b has been shown to control the expression of genes involved in fatty acid biosynthesis, impaired metabolism and insulin resistance. In this study, we aimed to identify differences in circulating miR-33a/b levels according to age-related metabolic impairment and increased adiposity. Methods: This study included 80 individuals (30.2% with obesity, 70% females) classified according to insulin resistance (Stern's criteria) and age [young (20-39 years) and senior (40-59 years)]. Body fat was evaluated using bioelectrical impedance, biochemical markers by colorimetric, enzymatic and immuno-turbidimetry methods. TaqMan measures of circulating miR-33a and miR-33b with quantitative reverse transcription polymerase chain reaction in serum were assessed in association with clinical outputs. Results: Circulating miR-33a and miR-33b levels showed significant association with fatness, the lipid profile and biomarkers of impaired glucose metabolism. Both miR-33a and miR-33b were associated with visceral adiposity index in non-insulin resistance and insulin resistance individuals. More important, for miR-33a circulating levels in senior group, receiver operating characteristic curve analyses showed area under the curve 0.804 (p = 0.010; 95% confidence interval = 0.655-0.952). Conclusion: Ageing influenced the relationship of circulating miR-33a and miR-33b with insulin resistance and increased adiposity.

The aim of this study was to investigate the relationship between functional polymorphisms Gly482Ser in PPARGC1A and Pro12Ala in PPARG2 with the presence of obesity and metabolic risk factors. We included 375 individuals characterized as Mexican-Mestizos and classified by the body mass index (BMI). Body dimensions and distribution of body fat were measured. The HOMA-IR and adiposity indexes were calculated. Adipokines and metabolic profile quantification were performed by ELISA and routine methods. Genetic polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism analysis. A difference between obese and nonobese subjects in polymorphism PPARGC1A distribution was observed. Among obese individuals, carriers of genotype 482Gly/Gly were observed to have decreased body fat, BMI, and body fat ratio versus 482Ser/Ser carriers and increased resistin and leptin levels in carriers Gly+ phenotype versus Gly− phenotype. Subjects with PPARG2 Ala− phenotype (genotype 12Pro/Pro) showed a decreased HOMA-IR index versus individuals with Ala+ phenotype (genotypes 12Pro/Ala plus 12Ala/Ala). We propose that, in obese Mexican-Mestizos, the combination of alleles 482Ser in PPARGC1A and 12Pro in PPARG2 represents a reduced metabolic risk profile, even when the adiposity indexes are increased.

Background. In obesity there is a subclinical chronic low-grade inflammatory response where insulin resistance (IR) may develop. Chemerin is secreted in white adipose tissue and promotes low-grade inflammatory process, where it expressed CMKLR1 receptor. The role of chemerin and CMKLR1 in inflammatory process secondary to obesity is not defined yet. Methods. Cross-sectional study with 134 individuals classified as with and without obesity by body mass index (BMI) and IR. Body fat storage measurements and metabolic and inflammatory markers were measured by routine methods. Soluble chemerin and basal levels of insulin by ELISA and relative expression of CMKLR1 were evaluated with qPCR and 2−ΔΔCT method. Results. Differences (P < 0.05) were observed between obesity and lean individuals in body fat storage measurements and metabolic-inflammatory markers. Both CMKLR1 expression and chemerin levels were increased in obesity without IR. Soluble chemerin levels correlate with adiposity and metabolic markers (r = 8.8% to 38.5%), P < 0.05. Conclusion. The increment of CMKLR1 expression was associated with insulin production. Increased serum levels of chemerin in obesity were observed, favoring a dysmetabolic response. The results observed in this study suggest that both chemerin and CMKLR1 have opposite expression in the context of low-grade inflammatory response manifested in the development of IR.

Immunometabolism is a current issue that has shown relevance in recent years, because the way we understand the adipose tissue has shifted from simply being a site of energy storage to a very active endocrine organ, which dysregulation has a major impact on other systems, especially on the immune one. Understanding the molecular basis of the regulation of adipose tissue is essential to look for alternatives in the treatment and prognosis of obesity in future generations. In this regard, it is described that the immune system has great importance in physiological processes of adipose tissue and vice versa. The main objective of this chapter is to describe the relationship between the immune system and metabolism, emphasizing dysregulation when obesity is present. Upon completion of this chapter, the reader will be able to understand the relationship between the immune system and metabolism, in normal and obesity states; also, will identify the chronic state of low-grade inflammation as the main etiological factor of obesity co-morbidities, such as insulin resistance, diabetes mellitus, osteoarthritis and susceptibility to some kinds of cancer, among others.