Serum levels of the novel adipokine isthmin-1 are associated with obesity in pubertal boys

Francisco Javier Ruiz-Ojeda; Augusto Anguita-Ruiz; Maria C Rico; Rosaura Leis; Gloria Bueno; Luis A Moreno; Mercedes Gil-Campos; Ángel Gil; Concepción M Aguilera

doi:10.1007/s12519-022-00665-8

Serum levels of the novel adipokine isthmin-1 are associated with obesity in pubertal boys

World J Pediatr. 2023 Sep;19(9):864-872. doi: 10.1007/s12519-022-00665-8. Epub 2023 Jan 3.

Authors

Francisco Javier Ruiz-Ojeda^{1

2

3

4}, Augusto Anguita-Ruiz^{5

6

7

8}, Maria C Rico^{9

10}, Rosaura Leis^{11

12

13

14}, Gloria Bueno^{11

15

16

17}, Luis A Moreno^{11

15

16}, Mercedes Gil-Campos^{11

18}, Ángel Gil^{9

19

10

11}, Concepción M Aguilera^{9

19

10

11}

Affiliations

¹ Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Granada, Spain. fruizojeda@ugr.es.
² Instituto de Investigación Biosanitaria Ibs.GRANADA, 18012, Granada, Spain. fruizojeda@ugr.es.
³ Institute of Nutrition and Food Technology "José Mataix", Center of Biomedical Research, University of Granada, Avda. del Conocimiento S/N. 18016 Armilla, Granada, Spain. fruizojeda@ugr.es.
⁴ RG Adipocytes and Metabolism, Institute for Diabetes and Obesity, Helmholtz Center Munich, 85764, Munich, Germany. fruizojeda@ugr.es.
⁵ Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Granada, Spain. augusto.anguita@isglobal.org.
⁶ Instituto de Investigación Biosanitaria Ibs.GRANADA, 18012, Granada, Spain. augusto.anguita@isglobal.org.
⁷ Institute of Nutrition and Food Technology "José Mataix", Center of Biomedical Research, University of Granada, Avda. del Conocimiento S/N. 18016 Armilla, Granada, Spain. augusto.anguita@isglobal.org.
⁸ Barcelona Institute for Global Health, ISGlobal, 08003, Barcelona, Spain. augusto.anguita@isglobal.org.
⁹ Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Granada, Spain.
¹⁰ Institute of Nutrition and Food Technology "José Mataix", Center of Biomedical Research, University of Granada, Avda. del Conocimiento S/N. 18016 Armilla, Granada, Spain.
¹¹ CIBEROBN, (Physiopathology of Obesity and Nutrition CB12/03/30038), Institute of Health Carlos III (ISCIII), 28029, Madrid, Spain.
¹² Unit of Investigation in Human Nutrition, Growth and Development of Galicia (GALINUT), University of Santiago de Compostela (USC), Santiago de Compostela, Spain.
¹³ Pediatric Nutrition Research Group, Institute of Sanitary Research of Santiago de Compostela (IDIS) CHUS-USC, 15706, Santiago de Compostela, Spain.
¹⁴ Unit of Pediatric Gastroenterology, Hepatology and Nutritio, Pediatric Service, University Clinical Hospital of Santiago (CHUS), 15706, Santiago de Compostela, Spain.
¹⁵ GENUD Research group, Institute of Sanitary Research of Aragón (IIS Aragón), University of Zaragoza, Zaragoza, Spain.
¹⁶ Instituto Agroalimentario de Aragón (IA2), Universidad de Zaragoza-CITA, Zaragoza, Spain.
¹⁷ Unit of Pediatric Endocrinology, University Clinical Hospital Lozano Blesa, 50009, Zaragoza, Spain.
¹⁸ Metabolism and Investigation Unit, Reina Sofia University Hospital, Maimónides Institute of Biomedicine Research of Córdoba (IMIBIC), University of Córdoba, 14071, Córdoba, Spain.
¹⁹ Instituto de Investigación Biosanitaria Ibs.GRANADA, 18012, Granada, Spain.

Abstract

Objectives: To evaluate whether there is an association between the serum levels of the novel insulin-like adipokine isthmin-1 (ISM1) and obesity-related phenotypes in a population of Spanish children and to investigate the plausible molecular alterations behind the alteration of the serum levels of this protein in children with obesity.

Methods: The study population is a sub-cohort of the PUBMEP research project, consisting of a cross-sectional population of 119 pubertal children with overweight (17 boys, 19 girls), obesity (20 boys, 25 girls), and normal weight (17 boys, 21 girls). All subjects were classified into experimental groups according to their sex, obesity, and insulin resistance (IR) status. They were counted anthropometry, glucose and lipid metabolism, inflammation and cardiovascular biomarkers as well as isthmin-1 (ISM1) serum levels. This population was intended as a discovery population to elucidate the relationship between obesity and ISM1 levels in children. Furthermore, the study population had blood whole-genome DNA methylation examined, allowing deepening into the obesity-ISM1 molecular relationship.

Results: Higher serum ISM1 levels were observed in boys with obesity than in normal weight (P = 0.004) and overweight (P = 0.007) boys. ISM1 serum levels were positively associated with body mass index (BMI) Z-score (P = 0.005) and fat mass (P = 0.058) and negatively associated with myeloperoxidase (MPO) (P = 0.043) in boys. Although we did not find associations between ISM1 serum levels and metabolic outcomes in girls, which may indicate a putative sexual dimorphism, fat mass was positively associated in all children, including boys and girls (P = 0.011). DNA methylation levels in two-enhancer-related CpG sites of ISM1 (cg03304641 and cg14269097) were associated with serum levels of ISM1 in children.

Conclusions: ISM1 is associated with obesity in boys at the pubertal stage, elucidating how this protein might be of special relevance as a new biomarker of obesity in children. Further studies including a longitudinal design during puberty are needed.

Keywords: Children; Epigenetics; Isthmin-1; Obesity; Puberty.

MeSH terms

Adipokines* / blood
Adolescent
Body Mass Index
Cross-Sectional Studies
Female
Humans
Male
Overweight
Pediatric Obesity* / epidemiology
Puberty
Thrombospondins / blood

Substances

Adipokines
ISM1 protein, human
Thrombospondins

Abstract

MeSH terms

Substances

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