Etual Espinosa1, Latife Salame1, Daniel Marrero-Rodriguez2, Andy-Michel Romero-Nieves3, Dalia Cuenca1, Osvaldo-Daniel Castelan-Martínez4, Victoria Mendoza1, Gustavo Ponce-Navarrete2, Mauricio Salcedo2, Enrique Luque-Leòn, Arturo Rodriguez-Gonzalez, Moisés Mercado5. 1. Endocrinology Service/Experimental Endocrinology Unit and Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Juárez, Mexico. 2. Obesity Clinic Hospital de Especialidades and Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Juárez, Mexico. 3. Oncology Research Unit, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Juárez, Mexico. 4. Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Zaragoza, Mexico. 5. Endocrinology Service/Experimental Endocrinology Unit and Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Juárez, Mexico. moises.mercado@endocrinologia.org.mx.
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.
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.
Authors: Sophie E Ter Hark; Stéphane Jamain; Dick Schijven; Bochao D Lin; Mark K Bakker; Anne Boland-Auge; Jean-François Deleuze; Réjane Troudet; Anil K Malhotra; Sinan Gülöksüz; Christiaan H Vinkers; Bjørn H Ebdrup; René S Kahn; Marion Leboyer; Jurjen J Luykx Journal: J Psychopharmacol Date: 2020-03-04 Impact factor: 4.153