Genetic Variants in the Activation of the Brown-Like Adipocyte Pathway and the Risk for Severe Obesity
Background: Regular physical activity has an important role in energy expenditure and combats the development of obesity. During exercise, PPARGC1A is overexpressed, stimulating an increase of the expression of FNDC5. This protein is cleaved to release the hormone irisin, which activates a browning...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Karger Publishers
2020-04-01
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| Series: | Obesity Facts |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/505666 |
| _version_ | 1818617686044704768 |
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| author | Ana Carolina Proença da Fonseca Guilherme Proença da Fonseca Bruna Marchesini Danielle Dutra Voigt Mario Campos Junior Verônica Marques Zembrzuski João Regis Ivar Carneiro José Firmino Nogueira Neto Pedro Hernan Cabello Giselda Maria Kalil Cabello |
| author_facet | Ana Carolina Proença da Fonseca Guilherme Proença da Fonseca Bruna Marchesini Danielle Dutra Voigt Mario Campos Junior Verônica Marques Zembrzuski João Regis Ivar Carneiro José Firmino Nogueira Neto Pedro Hernan Cabello Giselda Maria Kalil Cabello |
| author_sort | Ana Carolina Proença da Fonseca |
| collection | DOAJ |
| description | Background: Regular physical activity has an important role in energy expenditure and combats the development of obesity. During exercise, PPARGC1A is overexpressed, stimulating an increase of the expression of FNDC5. This protein is cleaved to release the hormone irisin, which activates a browning process in white adipose tissue through an increase in UCP1 expression. As a result, irisin leads to mitochondrial heat production and energy expenditure. Objectives:The aim of this study was to investigate whether genetic variants in genes related to browning are associated with severe obesity and obesity-related features. This case-control study comprised 210 individuals with severe obesity (median body mass index [BMI] 45.6 [range 40.5–52.2]) and 191 normal-weight subjects (BMI 22.8 [21.1–23.9]). Methods: Genomic DNA was extracted from peripheral blood and the genotypes of the PPARGC1A(rs8192678, rs3736265, rs2970847, and rs3755863) and UCP1 (rs6536991 and rs12502572) genes were obtained using Taqman® assay. For the FNDC5 gene, screening of exons 3–5 as well as their intron-exon boundaries was performed using automatic sequencing. Results: Our results demonstrated that PPARGC1Ars2970847 and UCP1rs12502572 are associated with severe obesity. Furthermore, these polymorphisms influence anthropometric traits, such as BMI, body weight, and body adiposity index. Our findings also showed a dose-effect relationship between PPARGC1A rs8192678 and fasting plasma glucose. Finally, 5 rare mutations were identified in FNDC5, and 1 of these is a novel missense mutation. Conclusion: This study shows that genetic variants in the activation of brown-like adipocyte pathway play an important role in the susceptibility to severe obesity. |
| first_indexed | 2024-12-16T17:09:38Z |
| format | Article |
| id | doaj.art-d75b20e183344142a07185e2632859b0 |
| institution | Directory Open Access Journal |
| issn | 1662-4025 1662-4033 |
| language | English |
| last_indexed | 2024-12-16T17:09:38Z |
| publishDate | 2020-04-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Obesity Facts |
| spelling | doaj.art-d75b20e183344142a07185e2632859b02022-12-21T22:23:28ZengKarger PublishersObesity Facts1662-40251662-40332020-04-0113213014310.1159/000505666505666Genetic Variants in the Activation of the Brown-Like Adipocyte Pathway and the Risk for Severe ObesityAna Carolina Proença da FonsecaGuilherme Proença da FonsecaBruna MarchesiniDanielle Dutra VoigtMario Campos JuniorVerônica Marques ZembrzuskiJoão Regis Ivar CarneiroJosé Firmino Nogueira NetoPedro Hernan CabelloGiselda Maria Kalil CabelloBackground: Regular physical activity has an important role in energy expenditure and combats the development of obesity. During exercise, PPARGC1A is overexpressed, stimulating an increase of the expression of FNDC5. This protein is cleaved to release the hormone irisin, which activates a browning process in white adipose tissue through an increase in UCP1 expression. As a result, irisin leads to mitochondrial heat production and energy expenditure. Objectives:The aim of this study was to investigate whether genetic variants in genes related to browning are associated with severe obesity and obesity-related features. This case-control study comprised 210 individuals with severe obesity (median body mass index [BMI] 45.6 [range 40.5–52.2]) and 191 normal-weight subjects (BMI 22.8 [21.1–23.9]). Methods: Genomic DNA was extracted from peripheral blood and the genotypes of the PPARGC1A(rs8192678, rs3736265, rs2970847, and rs3755863) and UCP1 (rs6536991 and rs12502572) genes were obtained using Taqman® assay. For the FNDC5 gene, screening of exons 3–5 as well as their intron-exon boundaries was performed using automatic sequencing. Results: Our results demonstrated that PPARGC1Ars2970847 and UCP1rs12502572 are associated with severe obesity. Furthermore, these polymorphisms influence anthropometric traits, such as BMI, body weight, and body adiposity index. Our findings also showed a dose-effect relationship between PPARGC1A rs8192678 and fasting plasma glucose. Finally, 5 rare mutations were identified in FNDC5, and 1 of these is a novel missense mutation. Conclusion: This study shows that genetic variants in the activation of brown-like adipocyte pathway play an important role in the susceptibility to severe obesity.https://www.karger.com/Article/FullText/505666polymorphismirisinsevere obesityucp1ppargc1a |
| spellingShingle | Ana Carolina Proença da Fonseca Guilherme Proença da Fonseca Bruna Marchesini Danielle Dutra Voigt Mario Campos Junior Verônica Marques Zembrzuski João Regis Ivar Carneiro José Firmino Nogueira Neto Pedro Hernan Cabello Giselda Maria Kalil Cabello Genetic Variants in the Activation of the Brown-Like Adipocyte Pathway and the Risk for Severe Obesity Obesity Facts polymorphism irisin severe obesity ucp1 ppargc1a |
| title | Genetic Variants in the Activation of the Brown-Like Adipocyte Pathway and the Risk for Severe Obesity |
| title_full | Genetic Variants in the Activation of the Brown-Like Adipocyte Pathway and the Risk for Severe Obesity |
| title_fullStr | Genetic Variants in the Activation of the Brown-Like Adipocyte Pathway and the Risk for Severe Obesity |
| title_full_unstemmed | Genetic Variants in the Activation of the Brown-Like Adipocyte Pathway and the Risk for Severe Obesity |
| title_short | Genetic Variants in the Activation of the Brown-Like Adipocyte Pathway and the Risk for Severe Obesity |
| title_sort | genetic variants in the activation of the brown like adipocyte pathway and the risk for severe obesity |
| topic | polymorphism irisin severe obesity ucp1 ppargc1a |
| url | https://www.karger.com/Article/FullText/505666 |
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