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Influence of Peroxisome Proliferator-Activated Receptor (PPAR)-gamma Coactivator (PGC)-1 alpha gene rs8192678 polymorphism by gender on different health-related parameters in healthy young adults.

ABSTRACT: This study aimed to analyze the influence of the peroxisome proliferator-activated receptor (PPAR)-gamma coactivator (PGC)-1 alpha (PPARGC1A) gene rs8192678 C>T polymorphism on different health-related parameters in male and female young adults. The PPARGC1A gene rs8192678 polymorphism was ascertained by polymerase chain reaction in 74 healthy adults (28 women; 22.72 ± 4.40 years) from Andalusia (Spain). Health-related variables included cardiometabolic risk, anthropometry and body composition, biochemical parameters, insulin sensitivity (QUICKI and HOMA-IR indexes), blood pressure (BP) at rest and after exercise, diet, basal metabolism, physical activity, maximal fat oxidation, and cardiorespiratory fitness. Our results showed differences by PPARGC1A gene rs8192678 C>T polymorphism in body mass (p = 0.002), body mass index (p = 0.024), lean body mass (p = 0.024), body fat (p = 0.032), waist circumference (p = 0.020), and BP recovery ratio (p < 0.001). The recessive model (CC vs. CT/TT) showed similar results but also with differences in basal metabolism (p = 0.045) and total energy expenditure (p = 0.024). A genotype*sex interaction was found in the QUICKI index (p = 0.016), with differences between CC and CT/TT in men (p = 0.049) and between men and women inside the CT/TT group (p = 0.049). Thus, the PPARGC1A gene rs8192678 C>T polymorphism is associated with body composition, basal metabolism, total energy expenditure, and BP recovery, where the CC genotype confers a protective effect. Moreover, our study highlighted sexual dimorphism in the influence of PPARGC1A gene rs8192678 C>T polymorphism on the QUICKI index.

SUBMITTER: Montes-de-Oca-Garcia A

PROVIDER: S-EPMC9354774 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Influence of Peroxisome Proliferator-Activated Receptor (PPAR)-gamma Coactivator (PGC)-1 alpha gene rs8192678 polymorphism by gender on different health-related parameters in healthy young adults.

Montes-de-Oca-García Adrián A Corral-Pérez Juan J Velázquez-Díaz Daniel D Perez-Bey Alejandro A Rebollo-Ramos María M Marín-Galindo Alberto A Gómez-Gallego Félix F Calderon-Dominguez Maria M Casals Cristina C Ponce-González Jesús G JG

Frontiers in physiology 20220722

This study aimed to analyze the influence of the peroxisome proliferator-activated receptor (PPAR)-gamma coactivator (PGC)-1 alpha (PPARGC1A) gene rs8192678 C>T polymorphism on different health-related parameters in male and female young adults. The PPARGC1A gene rs8192678 polymorphism was ascertained by polymerase chain reaction in 74 healthy adults (28 women; 22.72 ± 4.40 years) from Andalusia (Spain). Health-related variables included cardiometabolic risk, anthropometry and body composition, ...[more]

PMID: 35936915

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Project description:PGC-1a is a transcriptional coactivator known to regulate a broad gene program of nutrient and mitochondrial metabolism. Many splice variants of this protein have been identified, but their functions were unknown. This experiment was designed to delineate the downstream targets of two different PGC-1alpha isoforms (PGC-1a1 and PGC-1a4) in hepatocytes, and to determine whether inflammatory signaling (via TNFR activation) modulated these targets Liver is exposed to constantly changing metabolic and inflammatory environments. It must quickly sense and adapt to metabolic need while balancing resources required to protect itself from harmful inflammatory molecules. PGC-1α is a transcriptional coactivator that mediates cellular adaptation to diverse stimuli including inflammation. PGC-1α has a protective role against inflammation in several organs, including brain, heart, kidney, muscle, and liver. However, it is not known how hepatic PGC-1α integrates extracellular signals to mitigate inflammatory outcomes. PGC-1α exists as multiple, alternatively spliced variants whose expression is differentially regulated by different gene promoters. In human liver, we found that inflammatory conditions preferentially activated the alternative versus proximal PPARGC1A promoter. Gene expression analysis performed in primary mouse hepatocytes identified many shared and isoform-specific roles for PGC-1α variants during acute inflammation. PGC-1α1 primarily impacted gene programs of nutrient and mitochondrial metabolism, while TNFα treatment revealed that PGC-1α4 uniquely influenced several pathways related to innate immunity and cell death. Gain- and loss-of-function models showed that PGC-1α4 specifically attenuated apoptosis in response to TNFα or LPS, in contrast to PGC-1α1, which reduced expression of a wide inflammatory gene network. We conclude that PGC-1α variants have distinct, yet complimentary roles in hepatic responses to inflammation, with PGC-1α4 being an important mitigator of apoptosis.

Dataset Information

Influence of Peroxisome Proliferator-Activated Receptor (PPAR)-gamma Coactivator (PGC)-1 alpha gene rs8192678 polymorphism by gender on different health-related parameters in healthy young adults.

Publications

Influence of Peroxisome Proliferator-Activated Receptor (PPAR)-gamma Coactivator (PGC)-1 alpha gene rs8192678 polymorphism by gender on different health-related parameters in healthy young adults.

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