Omental adipose tissue gene expression, gene variants, branched-chain amino acids, and their relationship with metabolic syndrome and insulin resistance in humans

Abstract

Obesity is a complex disorder caused by several factors. Thus, the aim of the present study was to assess whether the expression of genes in the omental white adipose tissue (AT) of subjects with insulin resistance (IR) or metabolic syndrome (MetS) is associated with an elevation in serum branched-chain amino acids (BCAAs) and whether this response depends on specific genetic variants. Serum BCAA concentration, the adipocyte area, and gene variants of PPARγ, ABCA1, FTO, TCF7L2, GFOD2, BCAT2, and BCKDH were determined in 115 Mexican subjects. The gene expression in the AT and adipocytes of BCAT, BCKDH E1α, C/EBPα, PPARγ2, SREBP-1, PPARα, UCP1, leptin receptor, leptin, adiponectin, and TNFα was measured in 51 subjects. Subjects with IR showed higher values for the BMI, HOMA-IR, and adipocyte area and higher levels of serum glucose, insulin, leptin, and C-reactive protein, as well as an elevation of the AT gene expression of SREBP-1, leptin, and TNFα and a significant reduction in the expression of adiponectin, BCAT2, and BCKDH E1α, compared with non-IR subjects. The presence of MetS was associated with higher HOMA-IR as well as higher serum BCAA concentrations. Subjects with the genetic variants for BCAT2 and BCKDH E1 α showed a lower serum BCAA concentration, and those with the ABCA1 and FTO gene variant showed higher levels of insulin and HOMA-IR than non-IR subjects. AT dysfunction is the result of a combination of the presence of some genetic variants, altered AT gene expression, the presence of MetS risk factors, IR, and serum BCAA concentrations.

Figures

Fig. 1

Adipocyte area from the visceral adipose tissue of insulin (IR) and non-insulin resistance (non-IR) subjects. The white bars represent the adipocyte area from the subjects with IR, and the black bars represent those with non-IR. a Representative photographs of the adipocyte area from lean subjects, b subjects with both class III obesity (BMI 40 kg/m2) and IR, and c subjects with both class III obesity (BMI 62 kg/m2) and IR; the photographs show increased macrophage infiltration and crown-like structures

Fig. 2

Visceral adipose tissue and adipocyte mRNA gene expression of C/EBPα, PPARγ2, SREBP-1,leptin receptor (LR), leptin, adiponectin (AD), and TNFα. Black bars, subjects without insulin resistance (non-IR); white bars, subjects with insulin resistance (IR) *p < 0.05, **p < 0.01

Fig. 3

Associations between body mass index, HOMA-IR, BCCAs, omental adipose tissue BCAT, and BCKDH gene expression. a Bivariate correlation between HOMA-IR and BMI, r = 0.64 (Pearson test), p < 0.001. b Bivariate correlation between Σ BCAAs and HOMA-IR, r = 0.45 (Pearson test), p < 0.001. c Relationship between visceral adipose tissue gene expression of the BCKDH and BCAT2 in subjects with insulin resistance (IR) and non-insulin resistance (non-IR) *p < 0.05 (c)

Fig. 4

Association between HOMA-IR, metabolic syndrome and BCAA. Relationship between HOMA-IR and metabolic syndrome (MetS) risk factors (a). Relationship between HOMA-IR and MetS (b); Relationship between the Σ BCAAs and MetS (c). The white bars represent subjects with MetS, and the black bars represent those without MetS

Fig. 5

Relationship between Σ BCAAs and the presence of the genetic variants of BCKDH and BCAT2 *p < 0.05 (a). Relationship between insulin and HOMA-IR and the presence of the genetic variants of ABCA1 and FTO (b) *p < 0.05

Fig. 6

Summary of the factors (e.g., genetic factors, biochemical factors, endocrine factors, and inflammatory markers) and physiological differences, gene expression, and environmental interactions cause AT dysfunction by initiating a sequence leading to adipocyte hypertrophy and inflammatory processes