Uncoupling Proteins Variants Are Linked to Hypercholesterolemia and Abdominal Obesity in Metabolically Unhealthy Women
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Updated: Jun 2, 2025
Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
Erika Sierra-Ruelas1,2, Nathaly Torres-Castillo1,2,3, Barbara Vizmanos1,2,4,5,6
1Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, Mexico.
Introduction:
It has been reported that even with the same body mass index (BMI); there are subjects with metabolically healthy (MH) or unhealthy (MUH) phenotype. The main determinants of the unhealthy phenotype are the type and distribution of fat, ectopic fat accumulation, genetics, and lifestyle factors. Uncoupling proteins (UCPs) disengage mitochondrial respiration from ATP synthesis and result in heat production, which in turn is related to energy expenditure and, thus, to fat mass accumulation. The association of the UCP1 3826A/G (rs1800592), UCP2 Ala55Val (rs660339), and UCP3 55C/T (rs1800849) variants with metabolic variables was evaluated according to metabolic phenotype in Mexican women.
Methods:
Women aged 18-65 years classified as normal weight (NW) or excessive weight (EW) according to their BMI (from 18.5 to <25 kg/m2 for NW, and from 25 to <40 kg/m2 for EW), were included. Participants were classified into two metabolic phenotypes: MH or MUH, respectively, based on ATP-III criteria and the homeostasis model assessment of insulin resistance (HOMA-IR). The genetic variants were determined by allelic discrimination using TaqMan® probes.
Results:
In participants with the UCP1 3826A/G variant, an increased risk of hypercholesterolemia was observed in those with the NW-MUH phenotype (OR = 5.09, 95% CI = 1.03-25.12, p = 0.017). The UCP2 Ala55Val variant in EW-MUH subjects was associated with higher abdominal obesity risk (OR = 3.23, 95% CI = 1.21-8.60, p = 0.019), while no associations were found with the UCP3 55C/T variant.
Conclusion:
UCP1 and UCP2 variants are related with hypercholesterolemia and visceral fat accumulation in women with MUH phenotype.
Introduction:
It has been reported that even with the same body mass index (BMI); there are subjects with metabolically healthy (MH) or unhealthy (MUH) phenotype. The main determinants of the unhealthy phenotype are the type and distribution of fat, ectopic fat accumulation, genetics, and lifestyle factors. Uncoupling proteins (UCPs) disengage mitochondrial respiration from ATP synthesis and result in heat production, which in turn is related to energy expenditure and, thus, to fat mass accumulation. The association of the UCP1 3826A/G (rs1800592), UCP2 Ala55Val (rs660339), and UCP3 55C/T (rs1800849) variants with metabolic variables was evaluated according to metabolic phenotype in Mexican women.
Methods:
Women aged 18-65 years classified as normal weight (NW) or excessive weight (EW) according to their BMI (from 18.5 to <25 kg/m2 for NW, and from 25 to <40 kg/m2 for EW), were included. Participants were classified into two metabolic phenotypes: MH or MUH, respectively, based on ATP-III criteria and the homeostasis model assessment of insulin resistance (HOMA-IR). The genetic variants were determined by allelic discrimination using TaqMan® probes.
Results:
In participants with the UCP1 3826A/G variant, an increased risk of hypercholesterolemia was observed in those with the NW-MUH phenotype (OR = 5.09, 95% CI = 1.03-25.12, p = 0.017). The UCP2 Ala55Val variant in EW-MUH subjects was associated with higher abdominal obesity risk (OR = 3.23, 95% CI = 1.21-8.60, p = 0.019), while no associations were found with the UCP3 55C/T variant.
Conclusion:
UCP1 and UCP2 variants are related with hypercholesterolemia and visceral fat accumulation in women with MUH phenotype.
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