The PTK2B Gene is Associated with Obesity, Adiposity, and Leptin Levels in Children and Adolescents

Overview

Journal iScience

Publisher Cell Press

Date 2024 Nov 5

PMID 39498303

Authors

Eva Prida

Raquel Perez-Lois

Pablo Jacome-Ferrer

Diego Munoz-Moreno

Beatriz Brea-Garcia

Maria Villalon

Veronica Pena-Leon

Rocio Vazquez-Cobela

Concepcion M Aguilera

Javier Conde-Aranda

Javier Costas

Ana Estany-Gestal

Mar Quinones

Rosaura Leis

Luisa Maria Seoane

Omar Al-Massadi

Affiliations

Soon will be listed here.

Abstract

Previous studies determined that Pyk2 is involved in several diseases in which the symptomatology presents alterations in energy balance. However, its role in obesity is poorly understood. To evaluate the metabolic role of the Pyk2 gene () in children and adolescents with obesity we measured its mRNA expression levels in peripheral blood mononuclear cells. For that we performed a cross-sectional study involving 130 Caucasian subjects that was divided into two groups according to BMI. Data showed increased mRNA expression in children and adolescents with obesity. Interestingly, a positive correlation has been found between the levels of with weight, BMI, BMI score, fat mass, waist circumference, waist to height ratio, diastolic blood pressure, and leptin. In addition, it is indicated that high levels of gene expression might be a predictor of obesity development. This work provides important insights into the previously undescribed role of Pyk2 in obesity.

References

Oliver P, Reynes B, Caimari A, Palou A . Peripheral blood mononuclear cells: a potential source of homeostatic imbalance markers associated with obesity development. Pflugers Arch. 2013; 465(4):459-68. DOI: 10.1007/s00424-013-1246-8. View

Petrov P, Bonet M, Reynes B, Oliver P, Palou A, Ribot J . Whole Blood RNA as a Source of Transcript-Based Nutrition- and Metabolic Health-Related Biomarkers. PLoS One. 2016; 11(5):e0155361. PMC: 4862680. DOI: 10.1371/journal.pone.0155361. View

Stevens G, Mathers C, Beard J . Global mortality trends and patterns in older women. Bull World Health Organ. 2013; 91(9):630-9. PMC: 3790210. DOI: 10.2471/BLT.12.109710. View

Konieczna J, Sanchez J, van Schothorst E, Torrens J, Bunschoten A, Palou M . Identification of early transcriptome-based biomarkers related to lipid metabolism in peripheral blood mononuclear cells of rats nutritionally programmed for improved metabolic health. Genes Nutr. 2013; 9(1):366. PMC: 3896633. DOI: 10.1007/s12263-013-0366-2. View

Kelly A . Current and future pharmacotherapies for obesity in children and adolescents. Nat Rev Endocrinol. 2023; 19(9):534-541. DOI: 10.1038/s41574-023-00858-9. View

Giralt A, de Pins B, Cifuentes-Diaz C, Lopez-Molina L, Farah A, Tible M . PTK2B/Pyk2 overexpression improves a mouse model of Alzheimer's disease. Exp Neurol. 2018; 307:62-73. DOI: 10.1016/j.expneurol.2018.05.020. View

Caimari A, Oliver P, Rodenburg W, Keijer J, Palou A . Feeding conditions control the expression of genes involved in sterol metabolism in peripheral blood mononuclear cells of normoweight and diet-induced (cafeteria) obese rats. J Nutr Biochem. 2010; 21(11):1127-33. DOI: 10.1016/j.jnutbio.2009.10.001. View

Mosallaei M, Ehtesham N, Rahimirad S, Saghi M, Vatandoost N, Khosravi S . PBMCs: a new source of diagnostic and prognostic biomarkers. Arch Physiol Biochem. 2020; 128(4):1081-1087. DOI: 10.1080/13813455.2020.1752257. View

OGrada C, Morine M, Morris C, Ryan M, Dillon E, Walsh M . PBMCs reflect the immune component of the WAT transcriptome--implications as biomarkers of metabolic health in the postprandial state. Mol Nutr Food Res. 2013; 58(4):808-20. DOI: 10.1002/mnfr.201300182. View

10.

Ghoussaini M, Mountjoy E, Carmona M, Peat G, Schmidt E, Hercules A . Open Targets Genetics: systematic identification of trait-associated genes using large-scale genetics and functional genomics. Nucleic Acids Res. 2020; 49(D1):D1311-D1320. PMC: 7778936. DOI: 10.1093/nar/gkaa840. View

11.

Alves G, Aimaretti E, Einaudi G, Mastrocola R, de Oliveira J, Collotta D . Pharmacological Inhibition of FAK-Pyk2 Pathway Protects Against Organ Damage and Prolongs the Survival of Septic Mice. Front Immunol. 2022; 13:837180. PMC: 8843946. DOI: 10.3389/fimmu.2022.837180. View

12.

Tsiotra P, Pappa V, Raptis S, Tsigos C . Expression of the long and short leptin receptor isoforms in peripheral blood mononuclear cells: implications for leptin's actions. Metabolism. 2001; 49(12):1537-41. DOI: 10.1053/meta.2000.18519. View

13.

Buyken A, Karaolis-Danckert N, Remer T . Association of prepubertal body composition in healthy girls and boys with the timing of early and late pubertal markers. Am J Clin Nutr. 2008; 89(1):221-30. DOI: 10.3945/ajcn.2008.26733. View

14.

Mager U, Kolehmainen M, de Mello V, Schwab U, Laaksonen D, Rauramaa R . Expression of ghrelin gene in peripheral blood mononuclear cells and plasma ghrelin concentrations in patients with metabolic syndrome. Eur J Endocrinol. 2008; 158(4):499-510. DOI: 10.1530/EJE-07-0862. View

15.

Mukherjee S, Skrede S, Haugstoyl M, Lopez M, Ferno J . Peripheral and central macrophages in obesity. Front Endocrinol (Lausanne). 2023; 14:1232171. PMC: 10501731. DOI: 10.3389/fendo.2023.1232171. View

16.

Aksglaede L, Juul A, Olsen L, Sorensen T . Age at puberty and the emerging obesity epidemic. PLoS One. 2009; 4(12):e8450. PMC: 2793517. DOI: 10.1371/journal.pone.0008450. View

17.

Roca-Rivada A, Alonso J, Al-Massadi O, Castelao C, Peinado J, Seoane L . Secretome analysis of rat adipose tissues shows location-specific roles for each depot type. J Proteomics. 2011; 74(7):1068-79. DOI: 10.1016/j.jprot.2011.03.010. View

18.

Barja-Fernandez S, Lugilde J, Castelao C, Vazquez-Cobela R, Seoane L, Dieguez C . Circulating LEAP-2 is associated with puberty in girls. Int J Obes (Lond). 2020; 45(3):502-514. DOI: 10.1038/s41366-020-00703-3. View

19.

Goldstein S, Blecher M, Binder R, Perrino P, RECANT L . Hormone receptors, 5. Binding of glucagon and insulin to human circulating mononuclear cells in diabetes mellitus. Endocr Res Commun. 1975; 2(4-5):367-76. DOI: 10.1080/07435807509089009. View

20.

de Pins B, Mendes T, Giralt A, Girault J . The Non-receptor Tyrosine Kinase Pyk2 in Brain Function and Neurological and Psychiatric Diseases. Front Synaptic Neurosci. 2021; 13:749001. PMC: 8527176. DOI: 10.3389/fnsyn.2021.749001. View