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Expression of the growth hormone receptor isoforms and its correlation with the metabolic profile in morbidly obese subjects

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Abstract

Background and aim of the study

Given the lipolytic effect of GH and its potential role in determining adipose tissue distribution, we evaluated the expression of the GH hormone receptor (GHR) isoforms in patients with morbid obesity seeking associations with metabolic parameters.

Methods

262 morbidly obese subjects (mean age 42.5 ± 11 years, 75% women) underwent PCR-genotyping of the exon 3 GHR polymorphism. In 17 of these subjects, who proved to be heterozygous for the exon 3 genotype (+3/−3), subcutaneous and visceral adipose tissue was obtained during bariatric surgery; total RNA was extracted, reversely transcribed, and the different isoforms of the GHR (exon 3 containing and lacking flGHR as well as the trGHR) were PCR-amplified using specific primers.

Results

27% were +3/+3 homozygous, 20% −3/−3 homozygous and 53% were +3/−3 heterozygous. Compared to subjects homozygous for the +3 genotype, homozygous and heterozygous carriers of the −3 genotype were significantly heavier and tended to have a higher HOMA 2-IR. Expression of the flGHR and trGHR mRNA was demonstrated in all evaluated samples of subcutaneous and visceral adipose tissue from the 17 patients. The exon 3+ isoform was expressed in all adipose tissue samples, whereas only six subjects expressed the 3− isoform as well. The only distinctive feature of these six patients was a higher HbA1c.

Conclusions

The heterozygous GHR +3/−3 genotype is more prevalent in subjects with morbid obesity. Patients expressing the exon +3 and exon −3 isoforms in adipose tissue had a higher HbA1c, than those expressing only the exon −3 isoform.

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Funding

This study was funded by two institutional grants from Instituto Mexicano del Seguro Social: R-2013-3601-227 and R-2015-785-015.

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Authors and Affiliations

  1. Endocrinology Service/Experimental Endocrinology Unit and Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Juárez, Mexico

    Etual Espinosa, Latife Salame, Dalia Cuenca, Victoria Mendoza & Moisés Mercado

  2. Obesity Clinic Hospital de Especialidades and Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Juárez, Mexico

    Daniel Marrero-Rodriguez, Gustavo Ponce-Navarrete & Mauricio Salcedo

  3. Oncology Research Unit, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Juárez, Mexico

    Andy-Michel Romero-Nieves

  4. Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Zaragoza, Mexico

    Osvaldo-Daniel Castelan-Martínez

Authors
  1. Etual Espinosa
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  2. Latife Salame
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  3. Daniel Marrero-Rodriguez
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  9. Mauricio Salcedo
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  10. Enrique Luque-Leòn
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  11. Arturo Rodriguez-Gonzalez
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  12. Moisés Mercado
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Corresponding author

Correspondence to Moisés Mercado.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures involving human paricipants were in accordance to the ethical standards of the Institutional Research Committee and with the 1964 Helsinki Declaration and its later amendments.

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Informed consent was obtained from all individual participants.

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Espinosa, E., Salame, L., Marrero-Rodriguez, D. et al. Expression of the growth hormone receptor isoforms and its correlation with the metabolic profile in morbidly obese subjects. Endocrine 63, 573–581 (2019). https://doi.org/10.1007/s12020-018-1794-y

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  • DOI: https://doi.org/10.1007/s12020-018-1794-y

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