Determinants of Circulating Soluble Leptin Receptor and Free Leptin Index in Indonesian Pre-Pubertal Obese Male Children: A Preliminary Cross-Sectional Study

다국어 초록 (Multilingual Abstract)

Purpose: This study aimed to investigate the clinical and metabolic determinants of circulating soluble leptin receptor (CSLR) and free leptin index (FLI) in pre-pubertal obese male children.
Methods: We conducted a preliminary cross-sectional study at three tertiary hospitals and one public primary school. Eighty obese male children without growth and developmental abnormalities aged 5–9 years were recruited. In these children, obesity was solely caused by excessive food intake, and not by acute illness, medications, endocrine abnormalities, or any syndrome. Body mass index (BMI), body fat mass, carbohydrate intake, fat intake, high density lipoprotein cholesterol level, low density lipoprotein cholesterol level, triglyceride level, and Homeostatic Model Assessment for Insulin Resistance are the potential determinants for leptin regulation, which is represented by CSLR level and FLI.
Results: Carbohydrate was the main source of energy. BMI and body fat mass had negative weak correlation with CSLR and positive weak correlation with FLI. Furthermore, carbohydrate intake was found to be independently associated with CSLR based on the results of the multiple linear regression analysis. Following an increase in carbohydrate intake, CSLR level decreased progressively without any negative peak.
Conclusion: Leptin regulation in prepubertal obese male children is associated with body composition and dietary intake. Carbohydrate intake is useful for predicting CSLR. Lipid profiles and insulin resistance are not related to both CSLR and FLI. Treatment and prevention of leptin resistance in obese children should focus on reducing BMI, fat mass, and carbohydrate intake.

참고문헌 (Reference)

1 Rutters F, "The relationship between leptin, gonadotropic hormones, and body composition during puberty in a Dutch children cohort" 160 : 973-978, 2009

2 Austin PC, "The number of subjects per variable required in linear regression analyses" 68 : 627-636, 2015

3 Kennedy A, "The metabolic significance of leptin in humans : gender-based differences in relationship to adiposity, insulin sensitivity, and energy expenditure" 82 : 1293-1300, 1997

4 TANITA, "Tanita BC-545n: your digital personal trainer"

5 Mohan V, "Slowing the diabetes epidemic in the World Health Organization South-East Asia Region : the role of diet and physical activity" 5 : 5-16, 2016

6 Haluzík M, "Serum leptin levels in patients with hyperlipidemias" 16 : 429-433, 2000

7 Haluzík M, "Serum leptin concentrations in patients with combined hyperlipidemia : relationship to serum lipids and lipoproteins" 48 : 363-368, 1999

8 Weigle DS, "Roles of leptin and ghrelin in the loss of body weight caused by a low fat, high carbohydrate diet" 88 : 1577-1586, 2003

9 Shalitin S, "Role of obesity and leptin in the pubertal process and pubertal growth--a review" 27 : 869-874, 2003

10 Pandit R, "Role of leptin in energy expenditure : the hypothalamic perspective" 312 : R938-947, 2017

11 Indonesia. Badan Penelitian dan Pengembangan Kesehatan, "Riset kesehatan dasar: riskesdas, 2013" Badan Penelitian dan Pengembangan Kesehatan, Kementerian Kesehatan RI 2013

12 Wu DM, "Relationship between plasma leptin levels and lipid profiles among school children in Taiwan--the Taipei Children Heart Study" 17 : 911-916, 2001

13 Valle Jiménez M, "Relationship between changes in plasma leptin concentrations and plasminogen activator inhibitor-1 in obese prepubertal children after nine months of treatment" 63 : 216-222, 2013

14 Kavazarakis E, "Relation of serum leptin levels to lipid profile in healthy children" 50 : 1091-1094, 2001

15 Chan JL, "Regulation of circulating soluble leptin receptor levels by gender, adiposity, sex steroids, and leptin : observational and interventional studies in humans" 51 : 2105-2112, 2002

16 Harrell FE, "Regression modeling strategies: with applications to linear models, logistic regression and survival analysis" Springer 53-85, 2001

17 Silha JV, "Plasma resistin, adiponectin and leptin levels in lean and obese subjects : correlations with insulin resistance" 149 : 331-335, 2003

18 Slama FB, "Plasma levels of leptin and ghrelin and their correlation with BMI, and circulating lipids and glucose in obese Tunisian women" 9 : 161-168, 2015

19 Giovannucci E, "Nutritional predictors of insulin-like growth factor I and their relationships to cancer in men" 12 : 84-89, 2003

20 NutriSurvey, "Nutrition surveys and calculations"

21 Fadoua G, "Leptin, insulin and lipid profiles in obese subjects with and without metabolic syndrome in the region of Cap-Bon : Tunisia" 4 : 1-6, 2015

22 Romon M, "Leptin response to carbohydrate or fat meal and association with subsequent satiety and energy intake" 277 : E855-61, 1999

23 Sáinz N, "Leptin resistance and diet-induced obesity : central and peripheral actions of leptin" 64 : 35-46, 2015

24 Maffeis C, "Leptin concentration in newborns'cord blood : relationship to gender and growth-regulating hormones" 23 : 943-947, 1999

25 Gonzaga NC, "Leptin and cardiometabolic risk factors in obese children and adolescents" 50 : 707-712, 2014

26 Elias CF, "Leptin action in pubertal development : recent advances and unanswered questions" 23 : 9-15, 2012

27 Hill RA, "Leptin : its pharmacokinetics and tissue distribution" 22 : 765-770, 1998

28 Majid H, "Homeostatic model assessment for insulin resistance(HOMA-IR) : a better marker for evaluating insulin resistance than fasting insulin in women with polycystic ovarian syndrome" 27 : 123-126, 2017

29 Kong A, "Higher habitual intake of dietary fat and carbohydrates are associated with lower leptin and higher ghrelin concentrations in overweight and obese postmenopausal women with elevated insulin levels" 29 : 768-776, 2009

30 Kementerian Kesehatan, "Hasil utama RISKESDAS 2018" Kementerian Kesehatan Republik indonesia 2018

31 Rostami H, "Habitual dietary intake of fatty acids are associated with leptin gene expression in subcutaneous and visceral adipose tissue of patients without diabetes" 126 : 49-54, 2017

32 Maamra M, "Generation of human soluble leptin receptor by proteolytic cleavage of membrane-anchored receptors" 142 : 4389-4393, 2001

33 Iglesias MJ, "Gender differences in adiponectin and leptin expression in epicardial and subcutaneous adipose tissue. Findings in patients undergoing cardiac surgery" 59 : 1252-1260, 2006

34 Brabant G, "Free and protein bound leptin are distinct and independently controlled factors in energy regulation" 43 : 438-442, 2000

35 Barlow SEExpert Committee, "Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report" 120 (120): S164-192, 2007

36 Nishtar S, "Ending childhood obesity : a time for action" 387 : 825-827, 2016

37 R&D Systems, "ELISAs and ELISA Kits"

38 Obermann-Borst SA, "Duration of breastfeeding and gender are associated with methylation of the LEPTIN gene in very young children" 74 : 344-349, 2013

39 Harris RB, "Direct and indirect effects of leptin on adipocyte metabolism" 1842 : 414-423, 2014

40 Izadi V, "Dietary intakes and leptin concentrations" 10 : 266-272, 2014

41 UKK Nutrisi dan penyakit metabolik, "Diagnosis, tata laksana dan pencegahan obesitas pada anak dan remaja" Ikatan Dokter Anak Indonesia 2014

42 Kratzsch J, "Circulating soluble leptin receptor and free leptin index during childhood, puberty, and adolescence" 87 : 4587-4594, 2002

43 Myers MG Jr, "Challenges and opportunities of defining clinical leptin resistance" 15 : 150-156, 2012

44 Yannakoulia M, "Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans" 88 : 1730-1736, 2003

45 Sjarif DR, "Asuhan nutrisi pediatrik" Ikatan Dokter Anak Indonesia 2011

46 Brydon L, "Adiposity, leptin and stress reactivity in humans" 86 : 114-120, 2011

47 Jazet IM, "Adipose tissue as an endocrine organ : impact on insulin resistance" 61 : 194-212, 2003

48 Klöting N, "Adipocyte dysfunction, inflammation and metabolic syndrome" 15 : 277-287, 2014