Research Article| Volume 172, 108634, February 2021

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Are spexin levels associated with metabolic syndrome, dietary intakes and body composition in children?

  • Maryam Behrooz
    Student Research Committee, School of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Maraghe University of Medical Sciences, Department of Nutrition and Food Sciences, Department of Nutrition and Food Sciences, Iran
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  • Elnaz Vaghef-Mehrabany
    Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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  • Jalal Moludi
    School of Nutrition Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
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  • Alireza Ostadrahimi
    Corresponding author at: Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Attar Neyshabouri Av., Golgasht St., Tabriz, Iran.
    Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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Published:December 18, 2020DOI:


      • Spexin is a neuropeptide, with regulatory role in obesity and its co-morbiditie.
      • Spexin appears to have a positive impact on overall metabolic status in adolescents.
      • spexin, may have a positive impact on adipose tissue and adipose tissue metabolism.



      The aim of the present study was to investigate whether circulating levels of spexin is related to metabolic syndrome, some dietary intakes (Total energy intake, Macronutrient intakes) and body composition in children.


      90 children were recruited in the present cross sectional study. Anthropometric measures, body composition, blood pressure, dietary intakes, resting metabolic rate, physical activity level, appetite status, pubertal stage, serum spexin, fasting blood glucose, high-sensitivity C-reactive protein, insulin and lipid profile were measured using standard techniques.


      14 children met the criteria for metabolic syndrome. Median (IQR) of spexin levels were significantly lower in children with high fat mass and children with higher systolic blood pressure (SBP), compared to children with normal fat mass and normal SBP: (P < 0.05). A protective independent effect was detected for the highest tertile of serum spexin on metabolic syndrome in adjusted models; Crude OR (CI): 0.23 (0.04–1.2), P-trend = 0.08; Model 1: OR (CI): 0.15(0.02–1.01), P-trend = 0.05; Model 2: OR (CI): 0.10 (0.01–0.90), P-trend = 0.03. There was a significant negative association between spexin and total dietary fat intake (r= − 0.21; P < 0.04).


      This findings can further highlight the importance of the relationship between spexin, adipose tissue and adipose tissue metabolism.


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        • Kolodziejski P.A.
        • et al.
        Serum levels of spexin and kisspeptin negatively correlate with obesity and insulin resistance in women.
        Physiol Res. 2018; 67: 45-56
        • Kumar S.
        • et al.
        Decreased Circulating Levels of Spexin in Obese Children.
        J Clin Endocrinol Metab. 2016; 101: 2931-2936
        • Kumar S.
        • et al.
        Relationship of circulating spexin with markers of cardiovascular disease: a pilot study in adolescents with obesity.
        Pediatr Obes. 2018; 13: 374-380
        • Walewski J.L.
        • et al.
        Spexin is a novel human peptide that reduces adipocyte uptake of long chain fatty acids and causes weight loss in rodents with diet-induced obesity.
        Obesity (Silver Spring). 2014; 22: 1643-1652
        • Weiss R.
        • Gepstein V.
        Obesity as the main risk factor for metabolic syndrome in children.
        Front Endocrinol. 2019; 10: 568
        • Nehus E.
        • Mitsnefes M.
        Childhood obesity and the metabolic syndrome.
        Pediatric Clinics. 2019; 66: 31-43
        • Ogden C.L.
        • et al.
        Trends in Obesity Prevalence Among Children and Adolescents in the United States, 1988–1994 Through 2013–2014.
        JAMA. 2016; 315: 2292-2299
      1. Li, C., et al., Prevalence of pre-diabetes and its association with clustering of cardiometabolic risk factors and hyperinsulinemia among U.S. adolescents: National Health and Nutrition Examination Survey 2005-2006. Diabetes Care, 2009. 32(2): p. 342-7.

        • Dabelea D.
        • et al.
        Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009.
        JAMA. 2014; 311: 1778-1786
        • Lee A.M.
        • Gurka M.J.
        • DeBoer M.D.
        Trends in metabolic syndrome severity and lifestyle factors among adolescents.
        Pediatrics. 2016; 137
        • Friend A.
        • Craig L.
        • Turner S.
        The prevalence of metabolic syndrome in children: a systematic review of the literature.
        Metab Syndr Relat Disord. 2013; 11: 71-80
        • Kelishadi R.
        • et al.
        A systematic review on the prevalence of metabolic syndrome in Iranian children and adolescents.
        J Res Med Sci. 2016; 21: 90
        • Chen T.
        • et al.
        Circulating spexin decreased and negatively correlated with systemic insulin sensitivity and pancreatic β cell function in obese children.
        Ann Nutr Metab. 2019; 74: 125-131
        • Behrooz M.
        • Vaghef-Mehrabany E.
        • Ostadrahimi A.
        Different spexin level in obese vs normal weight children and its relationship with obesity related risk factors.
        Nutrit Metabol Cardiovas Dis. 2020; 30: 674-682
        • Cook S.
        • et al.
        Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988–1994.
        Arch Pediatr Adolesc Med. 2003; 157: 821-827
      2. Kuczmarski, R.J., et al., 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat 11, 2002(246): p. 1-190.

        • Montoye H.J.
        Energy costs of exercise and sport.
        in: Maughan R.G. Nutrition in sport. Blackwell Science Ltd, Oxford, UK2000: 53-72
        • Delshad M.
        • et al.
        Reliability and Validity of the Modifiable Activity Questionnaire for an Iranian Urban Adolescent Population.
        Int J Prev Med. 2015; 6
        • Sahebi A.
        • Asghari M.J.
        • Salari R.S.
        Validation of depression anxiety and stress scale (DASS-21) for an Iranian population.
        Iranian Psycholog. 2005; 4: 299-313
        • Flint A.
        • et al.
        Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies.
        Int J Obes Relat Metab Disord. 2000; 24: 38-48
        • Marshall W.A.
        • Tanner J.M.
        Variations in pattern of pubertal changes in girls.
        Arch Dis Child. 1969; 44: 291-303
        • Marshall W.A.
        • Tanner J.M.
        Variations in the pattern of pubertal changes in boys.
        Arch Dis Child. 1970; 45: 13-23
        • Matthews D.R.
        • et al.
        Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.
        Diabetologia. 1985; 28: 412-419
        • Ten S.
        • Maclaren N.
        Insulin resistance syndrome in children.
        J Clin Endocrinol Metab. 2004; 89: 2526-2539
        • Kurtoglu S.
        • et al.
        Insulin resistance in obese children and adolescents: HOMA-IR cut-off levels in the prepubertal and pubertal periods.
        J Clin Res Pediatr Endocrinol. 2010; 2: 100-106
        • Kelishadi R.
        • et al.
        First reference curves of waist and hip circumferences in an Asian population of youths: CASPIAN study.
        J Trop Pediatr. 2007; 53: 158-164
      3. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics, 2004. 114(2 Suppl 4th Report): p. 555-76.

        • Genuth S.
        • et al.
        Follow-up report on the diagnosis of diabetes mellitus.
        Diabet Care. 2003; 26: 3160-3167
        • Esfahani F.H.
        • et al.
        Reproducibility and relative validity of food group intake in a food frequency questionnaire developed for the Tehran Lipid and Glucose Study.
        J Epidemiol. 2010; 20: 150-158
        • Asghari G.
        • et al.
        Reliability, comparative validity and stability of dietary patterns derived from an FFQ in the Tehran Lipid and Glucose Study.
        Br J Nutr. 2012; 108: 1109-1117
        • Haugen H.A.
        • Chan L.N.
        • Li F.
        Indirect calorimetry: a practical guide for clinicians.
        Nutrit Clin Pract. 2007; 22: 377-388
        • Bitarafan V.
        • et al.
        Comparing serum concentration of spexin among patients with metabolic syndrome, healthy overweight/obese, and normal-weight individuals.
        Med J Islam Repub Iran. 2019; 33: 93
        • Al-Daghri N.M.
        • et al.
        Spexin Levels Are Associated with Metabolic Syndrome Components.
        Dis Markers. 2018; 2018: 1679690
        • Karaca A.
        • Bakar-Ates F.
        • Ersoz-Gulcelik N.
        Decreased spexin levels in patients with type 1 and type 2 diabetes.
        Med Principles Pract. 2018; 27: 549-554
        • Ge J.F.
        • et al.
        Regulation of Hepatocellular Fatty Acid Uptake in Mouse Models of Fatty Liver Disease with and without Functional Leptin Signaling: Roles of NfKB and SREBP-1C and the Effects of Spexin.
        Semin Liver Dis. 2016; 36: 360-372
        • Hodges S.K.
        • et al.
        Effect of obesity and type 2 diabetes, and glucose ingestion on circulating spexin concentration in adolescents.
        Pediatr Diabet. 2018; 19: 212-216
        • Kim D.-K.
        • et al.
        Coevolution of the spexin/galanin/kisspeptin family: Spexin activates galanin receptor type II and III.
        Endocrinology. 2014; 155: 1864-1873
        • Legakis I.
        • Mantzouridis T.
        • Mountokalakis T.
        Positive correlation of galanin with glucose in type 2 diabetes.
        Diabetes Care. 2005; 28: 759-760
        • Fang P.
        • et al.
        Galanin peptide family as a modulating target for contribution to metabolic syndrome.
        Gen Comp Endocrinol. 2012; 179: 115-120
        • Fang P.
        • et al.
        The potential antidepressant and antidiabetic effects of galanin system.
        Pharmacol Biochem Behav. 2014; 120: 82-87
        • Guo L.
        • et al.
        Galanin antagonist increases insulin resistance by reducing glucose transporter 4 effect in adipocytes of rats.
        Gen Comp Endocrinol. 2011; 173: 159-163
        • Alberti K.G.M.M.
        • Zimmet P.
        • Shaw J.
        Metabolic syndrome—a new world-wide definition. A consensus statement from the international diabetes federation.
        Diabet Med. 2006; 23: 469-480
        • Brunner S.M.
        • et al.
        GAL3 receptor KO mice exhibit an anxiety-like phenotype.
        Proc Natl Acad Sci U S A. 2014; 111: 7138-7143
        • Kolodziejski P.A.
        • et al.
        Spexin: A novel regulator of adipogenesis and fat tissue metabolism.
        Biochim Biophys Acta Mol Cell Biol Lipids. 2018; 1863: 1228-1236
        • Wong M.K.
        • et al.
        Goldfish spexin: solution structure and novel function as a satiety factor in feeding control.
        Am J Physiol Endocrinol Metab. 2013; 305: E348-E366
        • Gu L.
        • et al.
        Spexin peptide is expressed in human endocrine and epithelial tissues and reduced after glucose load in type 2 diabetes.
        Peptides. 2015; 71: 232-239
        • Al-Daghri N.M.
        • et al.
        Associations of Spexin and cardiometabolic parameters among women with and without gestational diabetes mellitus.
        Saudi J Biol Sci. 2018; 25: 710-714
        • Toll L.
        • et al.
        Peptides derived from the prohormone proNPQ/spexin are potent central modulators of cardiovascular and renal function and nociception.
        Faseb J. 2012; 26: 947-954