|Year : 2018 | Volume
| Issue : 1 | Page : 1-7
Studying a possible relationship among serum leptin, serum zinc and BMI in children
Lamia M Hafez1, Manal M.Abd El-Gawad2, Ola H Elgaddar3, Amenh B Yousif4
1 Regional Center for Food and Feed, Agriculture Research Center, Alexandria, Egypt
2 Department of Pediatrics, Faculty of Medicine, Alexandria University, Alexandria, Egypt
3 Department of Chemical Pathology, Medical Research Institute, Alexandria University, Alexandria, Egypt
4 Family and Community Medicine Department, Faculty of Medicine, Benghazi University, Benghazi, Libya
|Date of Web Publication||7-Sep-2018|
Lamia M Hafez
Regional Center for Food and Feed-Agriculture Research Center, Alexandria 21616
Source of Support: None, Conflict of Interest: None
Background Developing countries are facing the double burden of nutritional transition, malnutrition and micronutrient deficiencies, as well as a rapidly growing epidemic of childhood obesity. Leptin is a key hormone in the regulation of BMI, and a relation between zinc and leptin was detected.
Aim This study aimed to investigate the relationship among serum leptin, serum zinc and BMI in children.
Patients and methods A cross-sectional study was carried out on a total of 82 children of both sexes aged from 2 to 14 years attending the outpatient clinic at Alexandria University Children’s Hospital, Egypt, over 3 months from September 2016 to November 2016. All participants were clinically evaluated for weight, height and BMI. Serum leptin and serum zinc were measured.
Results From the total sample of 82 children, it was found that the high percent of overweight children were found in the age group between 9 and at least 14 in both sexes (48% in boys and 37.5% in girls). The mean serum leptin level was insignificantly higher in girls in the age group from 9 to up to 14 years; it was 10.67 μg in girls, whereas it was 9.0 in boys. There was no significant difference in serum zinc level between boys and girls at all age groups. There was an insignificant negative correlation between serum leptin and serum zinc in boys and girls at all age groups. The correlation between serum leptin and BMI was significantly positive in girls at age group 9 to up to 14 years (r=0.644, P=0.013). Serum zinc was insignificantly negatively correlated with BMI in boys and girls at age group 9 to up to 14 years, but the relation was positively significant in boys in the age group 2 to less than 3 (r=0.757, P=0.049).
Conclusion The correlation between leptin and BMI in girls was significant at age group 9 to up to 14 years. A negative insignificant correlation was found between serum leptin and serum zinc. Insignificant positive correlation was found between serum zinc and BMI.
Keywords: BMI, children, serum leptin, serum zinc
|How to cite this article:|
Hafez LM, El-Gawad MM, Elgaddar OH, Yousif AB. Studying a possible relationship among serum leptin, serum zinc and BMI in children. Alex J Pediatr 2018;31:1-7
|How to cite this URL:|
Hafez LM, El-Gawad MM, Elgaddar OH, Yousif AB. Studying a possible relationship among serum leptin, serum zinc and BMI in children. Alex J Pediatr [serial online] 2018 [cited 2019 Mar 25];31:1-7. Available from: http://www.ajp.eg.net/text.asp?2018/31/1/1/240744
| Introduction|| |
The prevalence of childhood overweight and obesity had risen worldwide by 47.1% between 1980 and 2013. The WHO reported that the global prevalence of childhood obesity had increased from 31 to 42 million children, and increased in Africa alone from 4 to 10 million children during the period from 1990 to 2013 .
Developing countries are facing the double burden of nutritional transition, malnutrition and micronutrient deficiencies, as well as a rapidly growing epidemic of childhood obesity .
Zinc is accepted as a trace element that is crucial in the growth of humans and many animal species . Zinc is said to be involved in the fat metabolism, insulin resistance and obesity, whereas zinc deficiency in animals is claimed to result in anorexia, weight loss, poor food efficiency and growth impairment ,. Zinc, which is an essential trace element, has also a role in the regulation of appetite. The fact that obese individuals have low zinc and high leptin levels suggests that there is a relation between zinc and nutrition, and consequently also between zinc and leptin ,,.
Zinc is a strong modulator of binding of amino acids to receptors associated with neurotransmission. The presence of zinc is a requisite for the synthesis of proteins that are necessary for the production of γ-aminobutyric acid which is known to stimulate food intake .
Recent studies exploring the relationship between zinc and leptin demonstrate that zinc may critically affect leptin secretion .
Leptin is a protein hormone that regulates food intake. It is secreted by the adipocytes and serves as a signal for the brain of the body’s energy store. Leptin controls food intake through its receptors in the hypothalamus by inhibiting the release of neuropeptide Y. The neuropeptide Y neurons are a key element in the regulation of hunger and have an augmentative effect on food intake. By reducing food intake and increasing thermogenesis, leptin is a key hormone in the regulation of body weight and nutrition . Levels of leptin in human blood correlate with BMI and fat mass, which led to weight loss by decreased food intake and increased energy expenditure . However, the notion of leptin as an anti-obesity hormone was called into question because obesity is typically associated with high leptin levels and not leptin deficiency. Moreover, rodents and humans that become obese on a high-fat (western) diet did not respond to leptin ,.
| Aim|| |
The study aimed to investigate the relationship among serum leptin, serum zinc levels and BMI in children of variable nutritional status.
A cross-sectional study was carried out on 82 children of both sexes aged from 2 to 14 years attending the outpatient clinic at Alexandria University Children Hospital, Egypt. The number of the study participants was selected using convenient sampling technique. They presented with acute various symptoms and variable BMI. The study was conducted over 4 months from September 2016 to December 2016.
- Children with syndromatic obesity.
- Children with endocrine disorders or any physical disability.
- Children with history of chronic medication use, use of mineral and/or vitamin supplements.
- Children with history of any chronic diseases.
- Children under special diets.
The study protocol was approved by the Ethical Committee of the Faculty of Medicine, Alexandria University, Egypt. Parents were provided with written informed consent to participate in the study.
| Methods|| |
- Data were collected using pretested questionnaire including, age, sex, weight and height for all participants. BMI was calculated for each participant, and the corresponding BMI percentile was obtained.
- Participants were informed to be fasting for 3 h before the second visit to collect blood sample for zinc and leptin measurements.
Height was measured without shoes using a Harpenden stadiometer (Harpenden; Holtain Ltd., Crosswell, UK) to the nearest 0.1 cm. Weight was measured to the nearest 0.1 kg on a standard beam scale with the individual dressed only in light wear and without shoes.
BMI was calculated by using BMI Percentile Calculator for Child and Teen Metric Version. BMI levels that define being normal weight or overweight are based on the child’s age and sex. The US Centers for Disease Control and Prevention has developed age-specific and sex-specific growth charts . These charts are used to translate a BMI value into a percentile. The percentiles are then used to determine the different weight groups:
- Underweight: less than the 5th BMI percentile.
- Normal weight: 5th percentile to less than the 85th BMI percentile.
- Overweight: 85th percentile to less than the 95th BMI percentile.
- Obese: 95th percentile or higher.
Serum zinc and serum leptin were measured in the Chemical Pathology Department, Medical Research Institute, Alexandria University, Egypt.
Serum leptin measurement
Serum leptin was measured using a commercially available enzyme-linked immune-sorbent assay kit, Diagnostic Biochem Canada Inc. (Ontario, London, Canada) for in vitro diagnostics. Measurement was done using a microwell plate reader (ELx80 Universal Microplate reader; Bio Tek Instruments,Winooski, Vermont, USA). The analytical measurement normal range of the assay is between 0.5 and 100 ng/ml .
Serum zinc measurement
Serum zinc concentration was estimated using an enzymatic method measured photometrically (Dialab, Wiener Neudorf, Austria), which is linear up to 400 μg/dl .
Statistical analysis of the data 
- Data were analyzed using SPSS software package version 16 (SPSS Inc., Chicago, Illinois, USA).
- Qualitative data were described using number and percent. Quantitative data were described using mean and SD.
- The Kolmogorov–Smirnov test and Shapiro–Wilk test were used to verify the normality of distribution. Normally quantitative data were expressed as mean±SD and compared using Student t-test, whereas the abnormally distributed data were expressed using median (minimum–maximum) and was compared using Mann–Whitney test.
- Correlation between variables was assessed by Pearson coefficient test. Significance of the obtained results was referred at a 5% level of significance.
| Results|| |
[Table 1] shows the demographic data of the studied 82 cases with an age range of 2–14 years. They were classified into two groups of boys and girls (50 boys and 32 girls), and each group was divided into three subgroups of age strata considering homogeneous distribution inside every age strata.
|Table 1 Distribution of the studied cases according to age strataa in the study groups|
Click here to view
[Table 2] shows nutritional status (as calculated by BMI percentiles) of the study population. High percent of overweight was found in the age group of 9 to at least 14 years in both sex (24 and 21.87% in boys and girls, respectively). No obese cases were recorded in the study groups.
|Table 2 Distribution of the participants according to BMI percentiles in the study groups|
Click here to view
[Table 3] shows the distribution of the studied cases according to their BMI. The numbers of normal weight, underweight and overweight were insignificantly different when both sexes were matched.
|Table 3 Comparison of the studied cases according to BMI percentiles in both groups of the study|
Click here to view
[Table 4] shows the mean±SD values of serum leptin and zinc in both groups of the study. Serum leptin was insignificantly higher in girls group in the age strata 9 to 14 years when matched with corresponding group of boys. Serum zinc was insignificantly different in both groups of the study in all age strata; however, it was higher in boys than girls in 9 to 14 years age strata.
|Table 4 Distribution and comparison of the studied cases according to serum leptin and serum zinc in both groups of the study|
Click here to view
[Table 5] shows the correlation between the mean value of serum leptin and serum zinc in relation to BMI in different age strata in both sexes.
|Table 5 Correlation between serum leptin, serum zinc, and BMI in both groups of the study in different age strata|
Click here to view
Serum leptin was significantly correlated with BMI in girls’ group of an age group 9 to 14 years (r=0.644, P=0.013) ([Figure 1]).
|Figure 1 Correlation between the mean value of serum leptin and BMI in girls in the age group 9 up to 14 years. r, Pearson coefficient. *P≤0.05, statistically significant.|
Click here to view
Serum zinc in boys of an age group 2 to 3 years was significantly and positively correlated with BMI (r=0.757, P=0.049) ([Figure 2]).
|Figure 2 Correlation between the mean value of serum zinc and BMI in boys in the age strata 2 up to 3 years.|
Click here to view
There was an insignificant negative correlation between serum leptin and serum zinc in boys and girls at all age strata. Hence, having normal serum zinc level is correlated with low serum leptin.
| Discussion|| |
The present work was designed to answer three important questions:
- The correlation − if any − between serum leptin and BMI.
- The correlation − if any − between serum zinc and BMI.
- The correlation − if any − between serum leptin and serum zinc.
Apparently healthy 82 children of both sexes with an age range of 2–14 years were classified according to their nutritional status and age strata all through the study.
First question: If there is a relation between serum leptin and BMI?
In the present study, number of overweight cases (as calculated by BMI percentiles) was numerically higher in the age strata 9 to up to 14 years in both sexes.
The current research found that serum leptin was insignificantly higher in the girls of an age strata 9 to up to 14 years, when matched with corresponding age strata in boys.
A significant positive correlation was found between serum leptin and overweight girls in the age group of 9 to up to 14 years. In other words, the serum leptin is increased when BMI increases. This finding of the current study contradicts what is accepted by many researchers, who speculate that leptin is the key to control obesity .
To explain the present study finding, many researches had proved that if greater amount of leptin is released (because of overweight or obesity) then it will be less effective on the brain for controlling hunger and food intake resulting in uncontrolled feeding, leading to greater food intake and further fat storage . Isidori et al.  reported that serum leptin levels increase with progressive obesity in both males and females, but for any given measure of obesity, leptin levels are higher in females than in males . This may be explained by the negative inflexion in leptin levels in boys which occurred after the testosterone levels rise, suggesting a direct inhibitory action of this steroid hormone on leptin production in boys in early puberty . Many investigators postulate that testosterone has a suppressive effect on leptin concentration in male individuals ,. Sexual dimorphism in circulating leptin concentrations is not observed during childhood or early puberty but is evident in later puberty, suggesting a relationship between leptin and gonadal steroids, body fat mass, BMI, and other anthropometric parameters . Other studies also found positive correlation between leptin levels and each of BMI, age and sex ,,,,. Comparable results of the study done on Tunisian children showed a positive correlation in all pubertal stages in girls but not in boys during puberty. It has been reported that in boys, there is a factor operating through puberty, as inhibitor of leptin, making leptin levels no longer a direct expression of the amount of adipose tissue present in boys . Furthermore, a larger study among European, African and Mexican–American populations reported the same finding .
Second question: If there is a relation between BMI and serum zinc?
The present study found that serum zinc was insignificantly and negatively correlated with BMI in both sexes included in the age strata 9 to up to 14 years. In other word, serum zinc is insignificantly decreased in the overweight early puberty boys and girls. In accordance with the present work results, Marreiro et al.  demonstrated a reduction of serum zinc in obese children. Furthermore, studies done in Greece and USA showed a negative correlation between serum zinc and BMI in obese children ,. On the contrary, zinc concentration was rather similar in both obese and nonobese children ,,.
A significant positive correlation was detected in the present work between serum zinc and boys 2 to less than 3 years of age irrespective of their BMI.
Zinc caused changes in appetite, and the most widely postulated mechanism is the alteration in hypothalamic neurotransmitter metabolism. Thus, the distinct possibility exists that zinc status could influence the regulation of appetite and metabolism by influencing the leptin system ,.
Third question: If there is a correlation between serum leptin and zinc?
The present study also found an insignificant negative correlation between serum leptin and serum zinc at all age groups in both sexes, which means that by increasing serum zinc, serum leptin will decrease. Furthermore, a study done on Egyptian children reported that serum leptin showed significant negative correlation with serum zinc levels in the obese children . This association could be explained by the effect of zinc-α2-glycoprotein (ZAG) on leptin concentrations. ZAG is an adipokine involved in lipolysis in the adipocyte that is down-regulated in obesity. In obese individuals, low ZAG gene expression is associated with low serum adiponectin and high plasma leptin levels, and may play an important role in the pathogenesis of obesity . Chen et al.  suggested in their study that leptin resistance that occurred in obesity might have resulted from zinc deficiency. The possible leptin-independent effect of zinc on ameliorating metabolic defect of obesity still cannot be totally ruled out.
| Conclusion|| |
The present study concluded the following:
- A positive correlation between serum leptin and BMI in girls in age group 9–14 years.
- An insignificant negative correlation between serum leptin and serum zinc at all age groups in both sexes.
The limitations of this study were the small sample size and the obese cases were not represented in the study population.
The authors like to express their appreciation to all children and their parents for their agreement to participate in the present study, and also express their gratitude to laboratory team of Medical Research Institute for the technical assistance and to all pediatrics hospital team who supported in the conduct of the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Farrag NS, Cheskin LJ, Farag MK. A systematic review of childhood obesity in the Middle East and North Africa (MENA) region: prevalence and risk factors meta-analysis. Adv Pediatr Res 2017; 4:1–17.
Wang Y, Lobstein T. Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes 2006;1:11–25.
Cole CR, Lifshitz F. Zinc nutrition and growth retardation. Pediatr Endocrinol Rev 2008;5:889–896.
Morley JE, Mooradian AD, Silver AJ, Heber D, Alfin-Slater RB. Nutrition in the elderly. Ann Intern Med 1988;109:890–904.
Su JC, Birmingham CL. Zinc supplementation in the treatment of anorexia nervosa. Eat Weight Disord 2002;7:20–22.
Essatara MB, Morley JE, Levine AS, Elson MK, Shafer RB, McClain CJ. The role of the endogenous opiates in zinc deficiency anorexia. Physiol Behav 1984;32:475–478.
Baltaci AK, Mogulkoc R, Halifeoglu I. Effects of zinc deficiency and supplementation on plasma leptin levels in rats. Biol Trace Elem Res 2005; 104:41–46.
Thaler JP, Schwartz MW. Minireview: Inflammation and obesity pathogenesis: the hypothalamus heats up. Endocrinology 2010;151:4109–4115.
Paul RF, Hassan M, Nazar S, Gillani S, Afzal N, Qayyum I. Effect of body mass index on serum leptin levels. J Ayub Med Coll Abbottabad 2011; 23:40–43.
Flier JS. Clinical review 94: what’s in a name? In search of leptin’s physiologic role. J Clin Endocrinol Metab 1998;83:1407–1413.
Heymsfield SB. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 1999;282:1568–1575.
Ogden CL, Flegal KM. Changes in terminology for childhood overweight and obesity. National health statistics reports; no 25. Hyattsville, MD: National Center for Health Statistics; 2010.
Ahamadi F, Bosorgmehr R, Razeghi E. Relationship between serum leptin level and laboratory and anthropometric indices of malnutrition in patients on hemodialysis. Indian J Nephrol 2008;18:105–111.
] [Full text]
Eliasson R, Johnsen R. Evaluation of a commercially available kit for the colorimetric determination of zinc. Int J Androl 1987;10:435–440.
Kotz S, Balakrishnan N, Read CB, Vidakovic B. Encyclopedia of statistical sciences. 2nd ed. Hoboken, NJ: Wiley-Interscience 2006.
Institute of Medicine (US) Panel on Micronutrients. Dietary reference intakes for vitamin a, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academies Press (US); 2001.
Mantzoros CS, Flier JS, Rogol AD. A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. V. Rising leptin levels may signal the onset of puberty. J Clin Endocrinol Metab 1997;82:1066–1070.
18.Ozata M, Ozdemir IC, Licinio J. Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J Clin Endocrinol Metab 1999; 84:3686–3695.
19.Isidori AM, Strollo F, Morè M, Caprio M, Aversa A, Moretti C et al.
Leptin and aging: correlation with endocrine changes in male and female healthy adult populations of different body weights. J Clin Endocrinol Metab 2000; 85:1954–1962.
Licinio J, Negrão AB, Mantzoros C. Sex differences in circulating human leptin pulse amplitude: clinical implications. J Clin Endocrinol Metab 1998;83:4140–4147.
Bronson FH. Food-restricted, prepubertal, female rats: rapid recovery of luteinizing hormone pulsing with excess food, and full recovery of pubertal development with gonadotropin-releasing hormone. Endocrinology 1986; 118:2483–2487.
Demerath EW, Towne B, Wisemandle W, Blangero J, Cameron Chumlea W, Siervogel M. Serum leptin concentration, body composition, and gonadal hormones during puberty. Int J Obes Relat Metab Disord 1999; 23:678–685.
Chehab FF, Lim ME, Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet 1996; 12:318–320.
Horlick MB, Rosenbaum M, Nicolson M, Levine LS, Fedun B, Wang J et al.
Effect of puberty on the relationship between circulating leptin and body composition. J Clin Endocrinol Metab 2000;85:2509–2518.
Brandão CM, Lombardi MT, Nishida SK, Hauache OM, Vieira JG. Serum leptin concentration during puberty in healthy non-obese adolescents. Braz J Med Biol Res 2003;36:1293–1296.
26.Bellone S, Rapa A, Petri A, Zavallone A, Strigini L, Chiorboli E et al.
Leptin levels as function of age, gender, auxological and hormonal parameters in 202 healthy neonates at birth and during the first month of life. J Endocrinol Invest 2004; 27:18–23.
27.Wilasco MI, Goldani HA, Dornelles CT, Maurer RL, Kieling CO, Porowski M et al.
Ghrelin, leptin and insulin in healthy children: relationship with anthropometry, gender, and age distribution. Regul Pept 2012; 173:21–26.
28.HorlickK MB, Rosenbaum M, Nicholson M, Levine LS, Fedun B, Wang J et al.
Effect of puberty on the relationship between circulating leptin and body composition. J Clin Endocrinol Metab 2000; 85:2509–2518.
29.Hassink SG, Sheslow DV, De Lancey E, Opentanova I, Considine RV, Caro JF. Serum leptin in children with obesity: relationship to gender and development. Pediatrics 1996; 98:201–203.
Jmal A, Bouyahya O, Ayadi I, Occhi H, Feki M, Kaabachi N et al.
Serum leptin concentration in Tunisian non overweight non obese children. Ann Biol Clin (Paris) 2010; 68:311–315.
Ellis KJ, Nicolson M. Leptin levels and body fatness in children: effects of gender, ethnicity, and sexual development. Pediatr Res 1997; 42:484–488.
Marreiro DD, Fisberg M, Cozzolino SM. Zinc nutritional status in obese children and adolescents. Bio Trace Elem Res 2002; 86:107–122.
Arvanitidou V, Voskaki I, Tripsianis G, Athanasopoulou H, Tsalkidis A, Filippidis S et al.
Serum copper and zinc concentrations in healthy children aged 3–14 years in Greece. Bio Trace Elem Res 2007; 115:1–12.
Fan Y, Zhang C, Bu J. Relationship between selected serum metallic elements and obesity in children and adolescent in the US. Nutrients 2017; 9:104–116.
Tascilar ME, Ozgen IT, Abaci A, Serdar M, Aykut O. Trace elements in obese Turkish children. Bio Trace Elem Res 2011; 143:188–195.
Weisstaub G, Hertrampf E, De Romana DL, Salazar G, Bugueno C, Castillo-Duran C. Plasma zinc concentration, body composition and physical activity in obese preschool children. Bio Trace Elem Res 2007; 118:167–174.
Kim HN, Song SW, Choi WS. Association between serum zinc level and body composition: The Korean National Health and Nutrition Examination Survey. Nutrition 2016; 32:332–337.
McClain G, Stuart M, Kasarskis E, Humphries L. Zinc, appetiteregulation and eating disorders. In: Prasad AS, editor. Essential and toxic trace elements in human health and disease: an update. New York, NY: Wiley -LissInc; 1993. pp. 47–64.
Ninh NX, Thissen JP, Collette L, Gerard G, Khoi HH, Ketelslegers JM. Zinc supplementation increases growth and circulating insulin-like growth factor I (IGF-I) in growth retarded Vietnamese children. Am J Clin Nutr 1996;63:514–519.
Azab SF, Saleh SH, Elsaeed WF, Elshafie MA, Sherief LM, Esh AM. Serum trace elements in obese Egyptian children: a case–control study. Ital J Pediatr 2014; 40:20–27.
Mracek T, Ding Q, Tzanavari T, Kos K, Pinkney J, Wilding J et al.
The adipokine zinc‐α2‐glycoprotein (ZAG) is downregulated with fat mass expansion in obesity. Clin Endocrin (Oxf) 2010; 72:334–341.
Chen MD, Lin PY. Zinc-induced hyperleptinemia relates to the amelioration of sucrose-induced obesity with zinc repletion. Obes Res 2000; 8:525–529.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]