Purpose Obesity results from excess energy intake over expenditure and is characterized by chronic low-grade inflammation involving circulating monocytes (Mo) and group 2 innate lymphoid cells (ILC2s) imbalance. We analyzed circulating Mo subsets and ILC2s percentages and β2-adrenergic receptor (β2AR) expression in lean and obese subjects, and the possible effect of hypocaloric restriction on these innate immune cells. Methods In 139 individuals aged 45 to 57 years, classified in 74 lean individuals (>18.9kg/m 2 BMI <24.9kg/m 2) and 65 with obesity (n = 65), we collected fasting blood samples to detect Mo subsets, ILC2s number, and β2AR expression by flow cytometry. Lipids, insulin, leptin, and acylated-ghrelin concentrations were quantified. Resting energy expenditure (REE) was estimated by indirect calorimetry. These measurements were repeated in obese subjects after 7-weeks of hypocaloric restriction. Results Non-classical monocytes (NCM) and β2AR expression on intermediate Mo (IM) were increased in obese individuals (p<0.001, in both cases), whereas the percent of ILC2s was decreased (p<0.0001). Stepwise regression analysis showed significantly negative associations of ILC2s with caloric intake, β2AR expression on IM with REE, but a positive relationship between NCM and HOMA-IR. Caloric restriction allowed a significant diminution of NCM and the β2AR expression on IM, as well as, an increase in the percent of classical Mo (CM), and ILC2s. ΔREE was related to ΔCD16 + /CD16ratio.

The enzyme nicotidamide-N-methyltransferase (NNMT) regulates adipose tissue energy expenditure through increasing nicotinamide adenosine dinucleotide (NAD + ) content. NNMT methylates nicotinamide to N 1 -methylnicotidamide (MNA-1) using S-adenosyl methionine. The rs 694539 NNMT polymorphism is associated with non-alcoholic steatohepatitis, and rs 1941404 is associated with hyperlipidemia. The rs 1421085 FTO is related to poor eating behaviors, and rs3751723 IRX3 is associated with obesity. To investigate the association of rs694539 and rs1941404 NNMT , rs140285 FTO and rs3751723 IRX3 polymorphisms with MNA-1 concentrations, resting energy expenditure (REE) and BMI, we included clinically healthy Mexican subjects 30 to 50 years old, 100 subjects (35 men/65 women) with BMI > 30 kg/m 2 and 100 subjects (32 men/68 women) with BMI < 25 kg/m 2 . Glucose, lipid profile, insulin, leptin, acylated ghrelin, and MNA-1 (LC–MS) were quantified. Resting energy expenditure (REE) was estimated using indirect calorimetry with a Fitmate instrument. Genotyping was performed using PCR–RFLP, and allelic discrimination was examined using TaqMan probes. MNA-1 concentrations and REE were significantly higher in obese subjects. Subjects with the rs694539AA NNMT genotype (recessive model) had lower weight, BMI, and REE. BMI showed an association with HDL-C, triglycerides, MNA-1, acetylated ghrelin, leptin, insulin concentrations, HOMA-IR, REE, and rs1421085. Subjects with the TC or CC genotypes of rs1421085 FTO showed 6 kg and 2 units of BMI more than did those with the TT wild type. The CG of the rs1421085 and rs3751723 haplotypes was associated with BMI. These findings showed that BMI was strongly associated with REE, rs1421085 FTO and the CG rs1421085 FTO and rs3751723 IRX3 haplotypes. We used the GMDR approach in obesity phenotype to show the interaction of four SNPs and metabolic variables.

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