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Breast milk leptin: its relationship to maternal and infant adiposity
Clinical Nutrition (2002) 21(2): 157–160 r 2002 Elsevier Science Ltd doi:10.1054/clnu.2001.0525, available online at http://www.idealibrary.com on
ORIGINAL ARTICLE
Breast milk leptin: its relationship to maternal and infant adiposity F. K. UYSAL,* E. E. $NAL,* Y. Z. ARAL,w B. ADAM,z U. DILMEN,* Y. ARDIC(OLUz *Department of Pediatrics, Fatih University Medical School, Ankara,Turkey; wDepartment of Pediatrics, Gazi University Medical School, Ankara,Turkey; zDepartment of Clinical Biochemistry, Fatih University Medical School, Ankara,Turkey (Correspondence to: EE$, 102.sok no:9/2 Birlik Mahallesi, 06610 C(ankaya, Ankara,Turkey)
AbstractFBackground and Aims: Leptin, the product of the obese gene (ob), is synthesized by adipose tissue and contributes to the regulation of energy homeostasis and food intake. Recently, immunoreactive leptin was reported to be present in human milk. The objective was to determine if there was a relation between breast milk leptin concentrations and adiposity in exclusively breast-fed infants. Methods: Fifty healthy, exclusively breast-fed infants beyond neonatal period, and their mothers were included into the study. Infants whose weight-for-length was above the 90th percentile were defined as obese (n=17), and non-obese if the weight for length between 20--90th percentile (n=33). Anthropometric measurements of infants and mothers were also made and breast milk samples were analyzed for leptin. Results: There was no significant difference between breast milk leptin concentrations of obese and non-obese infants’mothers. Breast milk leptin concentrations were significantly correlated with mothers’ body mass index when all subjects analyzed. There was no significant correlation between breast milk leptin concentrations and body mass index of infants. Conclusion: Leptin concentrations of human milk are not different in the mothers of obese and non-obese infants. These findings suggests that milk-borne leptin has no significant effect on adiposity during infancy. r 2002 Elsevier Science Ltd.
the range of normal plasma leptin concentrations and correlated with maternal body fat (9, 11). Additionally, it has been shown that oral administration of leptin mixed in milk led to a time-dependent increase of human leptin in serum of the neonatal rats, showing that their gastrointestinal tract was able to effectively absorb it in intact form. Therefore, the possibility that milk-derived leptin has an effect on infant growth and food intake raised (10). The aim of this study is determine whether breast milk leptin concentrations is related to adiposity in exclusively breast-fed infants.
Key words: leptin, breast-feeding, adiposity; infant
Introduction Leptin, the product of the obese gene (ob), is synthesized by adipose tissue and contributes to the regulation of energy homeostasis and food intake (1, 2). Plasma concentrations of leptin reflect body fat mass in adults and children and are markedly elevated in obese individuals, suggesting that most obese persons are insensitive to endogenous leptin production (3, 4). It is believed that leptin has function as a part of a signalling pathway from adipose tissue that acts to regulate the size of the body fat depot because leptin administration decreases food intake in rodents and nonhuman primates (1, 5). Furthermore, decreases in leptin during energy restriction in humans are related to increased sensations of hunger, suggesting that leptin also regulates appetite in humans (6). Leptin is also produced by the human placenta and is found in cord blood of newborns (7). Neonatal leptin concentrations are independent of maternal levels which suggests that placental leptin may play a role on fetal growth and development (8). Recently, immunoreactive leptin was reported to be present in human milk (9, 10). Concentrations of leptin in milk were lower than in plasma, but were still within
Subjects and methods Subjects Fifty healthy, exclusively breast-fed infants beyond neonatal period who admitted to pediatric outpatient clinic for their routine health control at the Department of Pediatrics of the Fatih University Medical School, Ankara, Turkey and their mothers were enrolled in the study. Infants whose weight-for-length was above the 90th percentile (group I, n=17) were consecutively included into the study and defined as obese. Group II, selected randomly, consisted of 33 non-obese infants whose weight-for-length between 20–90th percentile on the growth charts from World Health Organization statistics (12). Demographic features and morphometric 157
158
MILK LEPTIN CONCENTRATIONS AND INFANT OBESITY
indexes of infants were recorded. Weight was measured using an electronic scale (Seca Model 770, Hamburg, Germany), length (70,1 cm) was measured using a body-length measurer by a pediatric nurse who was unaware of the study. Breast milk was collected from mothers by electric pump for the first 5 min using Amedas breast pump 2 h after feeding the baby in the morning between 0800– 1100 am. Body weight, height and blood pressures of all mothers were measured and BMIs were calculated. All mothers were healthy and non-smokers. Women used any medication were excluded from the study. Informed written consent was obtained.
Table 1 Demographic features of study infants and mothers* Obese (n=17) Postnatal age (day) Sex (female/male) Birth weight (g) Birth length (cm) Gestational age (week) Mothers’ age (year)
97729 5/12 34167445 50.171.3 39.371.1 27.475.5
Non-obese (n=33) 92721 12/21 33677447 50.170.3 39.271.0 27.874.2
P value 0.813 0.621 0.782 0.974 0.678 0.585
*mean7SD
10 000 *P < 0.05
Leptin assay 8000 Body weight (g)
Collected milk samples were stored at 201C until assay. Samples were kept in refrigerator overnight for thawing before analysis, then were ultra-centrifuged at 15,000 rpm for 10 min at +41C to separate milk fat. The fat layer was removed by using a spatula and the liquid phase of the samples were used for the assay. Leptin levels were measured in duplicate using an 125 I-Radioimmunoassay (Sensitive Human Leptin RIA kit, Linco Research Inc, St. Charles, Mo, USA) and sample for quality control were included in each assay. The intra-assay coefficients of variation for the assay was 5.9% over the sample concentration range (13).
6000
4000
2000 1
2 Group
Statistical analysis w2 test was used for comparing nominal variables between groups and Mann–Whitney U test was used for numeric variables. Spearman bivariate correlation analysis was applied to calculate the correlation between breast milk leptin levels and BMIs of mothers and infants. All statistical calculations were performed by using SPSS program. A P value of o0.05 was considered statistically significant.
Fig. 1. Body weight measurements of infants at each month of age. Birth weight. Weight (1st month). Weight (2nd month)*. Weight (3rd month)*.
between breast milk leptin concentration and BMI of infants (Fig. 3). Birth weights and weights at the point of leptin assay of 8 cases whose mothers’ BMIs were equal or superior to 30 into obesity range, were not found greater than other infants whose mothers were not obese.
Results Although body weights of obese babies were significantly greater than non-obese infants at the point of leptin assay, there were no significant differences in birth weight, length and gestational age between groups (Table 1). Mean body weight measurements of subjects at each month of age were shown in Figure 1. Male/ female ratio was similar in both groups (Table 1). There was no significant difference in breast milk leptin concentrations between mothers of obese and non-obese infants (Table 2). Breast milk leptin concentrations were significantly correlated with mothers’ BMI when all subjects analyzed (Fig. 2). There was no significant correlation
Discussion We found that milk leptin concentrations of mothers of obese infants did not differ from mothers of non-obese infants. Serum leptin concentration is correlated positively with body weight, BMI, and percentage fat mass (2). Changes in serum leptin concentrations are also correlated with changes in weight and adiposity (3). Immunoreactive leptin has been detected in human infant cord blood (14, 15). Leptin concentrations in newborn are independent of maternal levels, therefore cord blood leptin is produced by the placenta and
CLINICAL NUTRITION
159
Table 2 Morphometric indexes at the point of leptin assay and breast milk leptin concentrations of subjects*
Weight (g) Height (cm) BMI of infants (kg/m2) BMI of mothers (kg/m2) Breast milk leptin concentrations (ng/ml)
Obese (n=17)
Non-obese (n=33)
P value
776071141 62.074.7 18.872.8 25.674.1 0.2770.2
63837889 63.9725.9 16.771.4 26.174.6 0.3770.4
0.001 0.578 0.000 0.841 0.984
*mean7SD
Skim milk leptin (ng/mL)
1.0 r = 0.62 P < 0.001 0.8 0.6 0.4 0.2 0.0 15
20
25
30
35
40
BMI (kg/m2) Fig. 2. Relationship between BMI of mothers and breast milk leptin concentrations.
2.0
Skim milk leptin (ng/mL)
r = 0.05 P = 0.72 1.5
1.0
0.5
0 8
10
12
14 16 BMI (kg/m2)
18
20
22
Fig. 3. Relationship between infants’ BMI and breast milk leptin concentrations.
potentially plays a role in fetal and neonatal growth (14–16). Human milk also contains immunoreactive leptin which is identical to intact human leptin (10). Smith– Kirwin et al. showed that human mammary epithelial cells express leptin (13). Leptin concentrations in human milk were correlated with maternal plasma leptin concentrations, but were one order of magnitude lower, maternal body weight, BMI and skinfold thickness which suggested that milk leptin concentrations reflect maternal adiposity (9). Obesity is characterized by an excess of adipose tissue in relation to lean body mass. Standardized definitions
of obesity for infants and children have not been developed. An age- and gender-specific weight-forheight in excess of the 90th percentile on the growth charts or weight in excess of 120% of the median weight for a given height is the traditional definition of obesity (17). Total body fat may be measured directly by hydrostatic weighing or by measuring absorption of gases by lipid tissue or the level of intracellular potassium. Although these methods are impractical in a clinical setting, they form the standards against which indirect methods are evaluated (18). Indirect methods of assessing obesity, including evaluation of the weight– height ratio and calliper measurement of the thickness of skin folds are less precise but less invasive (18). It has been shown that whole-body fat measured by total-body electrical conductivity was strongly correlated with weight-for-length and calf circumference, whereas skinfold thickness, body mass index and Ponderal indexes were poorly correlated with whole-body fat in infants (19). Consequently, we used weight-for-length measurement to define obesity in infants in this study, although it was a rough (but non-invasive) estimation of infant body composition. We showed that leptin concentrations of human milk were not different in obese and non-obese infants’ mothers. Additionally, breast milk leptin concentrations were correlated with maternal BMI but not with infants’ BMI. These findings suggested that milk-borne leptin has no significant effect on adiposity during infancy. These data is consistent with the study of Lo¨nnerdal (20). They reported that serum leptin concentrations were not significantly higher in breast-fed than in formula-fed infants. Thus, it appeared unlikely that leptin in breast milk was absorbed in physiologically relevant amounts, which in turn, would contribute to differences in growth and body composition in infancy (20). It has been showed that leptin concentrations of whole milk were much higher than of skim milk and fat in human milk interfered with the leptin assay. Therefore, we assessed leptin concentrations in skim milk and our results were similar to those in previous studies (13, 20). Although maternal obesity was reported to be associated with increased birth weight previously, we did not find any difference between birth weights and weights at the point of leptin assay of infants whose mothers’ BMIs were equal or superior to 30 into obesity
160
MILK LEPTIN CONCENTRATIONS AND INFANT OBESITY
range and infants whose mothers were not obese (21). This might be due to small number of obese mothers in this study. Human milk contains many hormones and growth factors. It has been proposed that many substances in breast milk may be important for development of the neonatal small intestine or play important roles on immune mechanisms. It is reported that leptin also has a specific effect on T-lymphocyte responses, differentially regulating the proliferation of naı¨ ve and memory Tcells, and increased IL-2 production and IFN-g secretion (22). Recently, leptin receptor was demonstrated to be present on gastric mucous cells and suggested that leptin might has paracrine effect (23). These observations suggest that leptin in breast milk may have different functions related directly to gastrointestinal system or immune system. In summary, breast milk leptin concentrations are not different in mothers of obese and non-obese infants. These findings suggests that milk-borne leptin has no significant effect on adiposity during infancy.
Acknowledgments This research is funded by Milupa.
References 1. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman J M. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425–432 2. Tartaglia L A. The leptin receptor. J Biol Chem 1997; 272(10): 6093–6096 3. Considine R V, Sinha M K, Heiman M L, Kriauciunas A, Stephens T W, Nyce M R, Ohannesian J P, Marco C C, McKee L J, Bauer T L. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Eng J Med 1996; 334: 292–295 4. Nagy T R, Gower B A, Trowbridge C A, Dezenberg C, Shewchuk R M, Goran M I. Effects of gender, ethnicity, body composition, and fat distribution on serum leptin concentrations in children. J Clin Endocrinol Metab 1997; 82: 2148–2152 5. Tang-Christensen M, Havel P J, Jacobs R R, Larsen P J, Cameron J L. Central administration of leptin inhibits food intake and activates the sympathetic nervous system in rhesus macaques. J Clin Endocrinol Metab 1999; 84: 711–717 6. Keim N L, Stern J S, Havel P J. Relationship between circulating leptin concentrations and appetite during a prolonged, moderate energy deficit in women. Am J Clin Nutr 1998; 68: 794–801 7. Senaris R, Garcia-Caballero T, Casabiell X, Gallego R, Castro R, Considine R V, Dieguez C, Casanueva F F. Synthesis of leptin in human placenta. Endocrinology 1997; 138: 4501–4505 Submission date: 6 July 2001 Accepted: 5 November 2001
8. Matsuda J, Yokota I, Iida M, Murakami T, Naito E, Ito M, Shima K, Kuroda Y. Serum leptin concentration in cord blood: relationship to birth weight and gender. J Clin Endocrinol Metab 1997; 82: 1642–1644 9. Houseknecht K L, McGuire M K, Portocarrero C P, McGuire M A, Beerman K. Leptin is present in human milk and is related to maternal plasma leptin concentrations and adiposity. Biochem Biophys Res Commun 1997; 240: 742–747 10. Casabiell X, Pineiro V, Tome M A, Peino R, Dieguez C, Casanueva F F. Presence of leptin in colostrum and/or breast milk from lactating mothers: a potential role in the regulation of neonatal food intake. J Clin Endocrinol Metab 1997; 82: 4270–4273 11. Ucar B, Kirel B, Bor O, Kilic F S, Dogruel N, Aydogdu S D, Tekin N. Breastmilk leptin concentrations in initial and terminal milk samples: relationships to maternal and infant plasma leptin concentrations, adiposity, serum glucose, insulin, lipid and lipoprotein levels. J Pediatr Endocrinol Metab 2000; 13(2): 149–156 12. Measuring change in nutritional status (Guidelines for assessing the nutritional impact of supplementary feeding programmes for vulnerable groups), World Health Organization, Geneva, 1983 13. Smith-Kirwin S M, O’Connor D M, Johnston J, De Lancey E, Hassink S G, Funanage V L. Leptin expression in human mammary epithelial cells and breast milk. J Clin Endocrinol Metab 1998; 83(5): 1810–1813 14. Helland I B, Reseland J E, Saugstad O D, Drevon C A. Leptin levels in pregnant women and newborn infants: Gender differences and reduction during the neonatal period. Pediatrics 1998; 101(3): e12 15. Shekhawat P S, Garland J S, Shivpuri C, Mick G J, Sasidharan P, Pelz C J, McCormick K L. Neonatal cord blood leptin: its relationship to birth weight, body mass index, maternal diabetes, and steroids. Pediat Res 1998; 43: 338–343 16. Hassink G S, Lancey E, Sheslow D V, Smith-Kirwin S M, O’Connor D M, Considine R V, Opentanova I, Dostal K, Spear M L, Leef K, Ash M, Spitzer A R, Funanage V L. Placental leptin: An important new growth factor in intrauterine and neonatal development? Pediatrics 1997; 100(1): e1 17. Schonfeld-Warden N, Warden C H. Pediatric obesity: An overview of etiology and treatment. Pediatr Clin North Am 1997; 44(2): 339–361 18. Leung A K C, Robson W L M. Childhood obesity. Postgrad Med 1990; 87: 123–130 19. De Bruin N C, van Velthoven K A, Stijnen T, Juttmann R E, Degenhart H J, Visser H K. Body fat and fat-free mass in infants: new and classic anthropometric indexes and prediction equations compared with total-body electrical conductivity. Am J Clin Nutr 1995; 61: 1195–1205 20. Lo¨nnerdal B, Havel P J. Serum leptin concentrations in infants: effects of diet, sex, and adiposity. Am J Clin Nutr 2000; 72: 484–489 21. Whitaker R C, Dietz W H. Role of prenatal environment in the development of obesity. J Pediatr 1998; 132: 768–776 22. Lord G M, Matarese G, Howard J K, Baker R J, Bloom S R, Lechler R I. Leptin modulates the T-cell immune response and reverses starvation-induced immunosupression. Nature 1998; 394: 897–900 23. Mix H, Manns M P, Wagner S, Widjaja A, Brabant G. Expression of leptin and its receptor in the human stomach. Gastroenterology 1999; 117: 509–510
ORIGINAL ARTICLE
Breast milk leptin: its relationship to maternal and infant adiposity F. K. UYSAL,* E. E. $NAL,* Y. Z. ARAL,w B. ADAM,z U. DILMEN,* Y. ARDIC(OLUz *Department of Pediatrics, Fatih University Medical School, Ankara,Turkey; wDepartment of Pediatrics, Gazi University Medical School, Ankara,Turkey; zDepartment of Clinical Biochemistry, Fatih University Medical School, Ankara,Turkey (Correspondence to: EE$, 102.sok no:9/2 Birlik Mahallesi, 06610 C(ankaya, Ankara,Turkey)
AbstractFBackground and Aims: Leptin, the product of the obese gene (ob), is synthesized by adipose tissue and contributes to the regulation of energy homeostasis and food intake. Recently, immunoreactive leptin was reported to be present in human milk. The objective was to determine if there was a relation between breast milk leptin concentrations and adiposity in exclusively breast-fed infants. Methods: Fifty healthy, exclusively breast-fed infants beyond neonatal period, and their mothers were included into the study. Infants whose weight-for-length was above the 90th percentile were defined as obese (n=17), and non-obese if the weight for length between 20--90th percentile (n=33). Anthropometric measurements of infants and mothers were also made and breast milk samples were analyzed for leptin. Results: There was no significant difference between breast milk leptin concentrations of obese and non-obese infants’mothers. Breast milk leptin concentrations were significantly correlated with mothers’ body mass index when all subjects analyzed. There was no significant correlation between breast milk leptin concentrations and body mass index of infants. Conclusion: Leptin concentrations of human milk are not different in the mothers of obese and non-obese infants. These findings suggests that milk-borne leptin has no significant effect on adiposity during infancy. r 2002 Elsevier Science Ltd.
the range of normal plasma leptin concentrations and correlated with maternal body fat (9, 11). Additionally, it has been shown that oral administration of leptin mixed in milk led to a time-dependent increase of human leptin in serum of the neonatal rats, showing that their gastrointestinal tract was able to effectively absorb it in intact form. Therefore, the possibility that milk-derived leptin has an effect on infant growth and food intake raised (10). The aim of this study is determine whether breast milk leptin concentrations is related to adiposity in exclusively breast-fed infants.
Key words: leptin, breast-feeding, adiposity; infant
Introduction Leptin, the product of the obese gene (ob), is synthesized by adipose tissue and contributes to the regulation of energy homeostasis and food intake (1, 2). Plasma concentrations of leptin reflect body fat mass in adults and children and are markedly elevated in obese individuals, suggesting that most obese persons are insensitive to endogenous leptin production (3, 4). It is believed that leptin has function as a part of a signalling pathway from adipose tissue that acts to regulate the size of the body fat depot because leptin administration decreases food intake in rodents and nonhuman primates (1, 5). Furthermore, decreases in leptin during energy restriction in humans are related to increased sensations of hunger, suggesting that leptin also regulates appetite in humans (6). Leptin is also produced by the human placenta and is found in cord blood of newborns (7). Neonatal leptin concentrations are independent of maternal levels which suggests that placental leptin may play a role on fetal growth and development (8). Recently, immunoreactive leptin was reported to be present in human milk (9, 10). Concentrations of leptin in milk were lower than in plasma, but were still within
Subjects and methods Subjects Fifty healthy, exclusively breast-fed infants beyond neonatal period who admitted to pediatric outpatient clinic for their routine health control at the Department of Pediatrics of the Fatih University Medical School, Ankara, Turkey and their mothers were enrolled in the study. Infants whose weight-for-length was above the 90th percentile (group I, n=17) were consecutively included into the study and defined as obese. Group II, selected randomly, consisted of 33 non-obese infants whose weight-for-length between 20–90th percentile on the growth charts from World Health Organization statistics (12). Demographic features and morphometric 157
158
MILK LEPTIN CONCENTRATIONS AND INFANT OBESITY
indexes of infants were recorded. Weight was measured using an electronic scale (Seca Model 770, Hamburg, Germany), length (70,1 cm) was measured using a body-length measurer by a pediatric nurse who was unaware of the study. Breast milk was collected from mothers by electric pump for the first 5 min using Amedas breast pump 2 h after feeding the baby in the morning between 0800– 1100 am. Body weight, height and blood pressures of all mothers were measured and BMIs were calculated. All mothers were healthy and non-smokers. Women used any medication were excluded from the study. Informed written consent was obtained.
Table 1 Demographic features of study infants and mothers* Obese (n=17) Postnatal age (day) Sex (female/male) Birth weight (g) Birth length (cm) Gestational age (week) Mothers’ age (year)
97729 5/12 34167445 50.171.3 39.371.1 27.475.5
Non-obese (n=33) 92721 12/21 33677447 50.170.3 39.271.0 27.874.2
P value 0.813 0.621 0.782 0.974 0.678 0.585
*mean7SD
10 000 *P < 0.05
Leptin assay 8000 Body weight (g)
Collected milk samples were stored at 201C until assay. Samples were kept in refrigerator overnight for thawing before analysis, then were ultra-centrifuged at 15,000 rpm for 10 min at +41C to separate milk fat. The fat layer was removed by using a spatula and the liquid phase of the samples were used for the assay. Leptin levels were measured in duplicate using an 125 I-Radioimmunoassay (Sensitive Human Leptin RIA kit, Linco Research Inc, St. Charles, Mo, USA) and sample for quality control were included in each assay. The intra-assay coefficients of variation for the assay was 5.9% over the sample concentration range (13).
6000
4000
2000 1
2 Group
Statistical analysis w2 test was used for comparing nominal variables between groups and Mann–Whitney U test was used for numeric variables. Spearman bivariate correlation analysis was applied to calculate the correlation between breast milk leptin levels and BMIs of mothers and infants. All statistical calculations were performed by using SPSS program. A P value of o0.05 was considered statistically significant.
Fig. 1. Body weight measurements of infants at each month of age. Birth weight. Weight (1st month). Weight (2nd month)*. Weight (3rd month)*.
between breast milk leptin concentration and BMI of infants (Fig. 3). Birth weights and weights at the point of leptin assay of 8 cases whose mothers’ BMIs were equal or superior to 30 into obesity range, were not found greater than other infants whose mothers were not obese.
Results Although body weights of obese babies were significantly greater than non-obese infants at the point of leptin assay, there were no significant differences in birth weight, length and gestational age between groups (Table 1). Mean body weight measurements of subjects at each month of age were shown in Figure 1. Male/ female ratio was similar in both groups (Table 1). There was no significant difference in breast milk leptin concentrations between mothers of obese and non-obese infants (Table 2). Breast milk leptin concentrations were significantly correlated with mothers’ BMI when all subjects analyzed (Fig. 2). There was no significant correlation
Discussion We found that milk leptin concentrations of mothers of obese infants did not differ from mothers of non-obese infants. Serum leptin concentration is correlated positively with body weight, BMI, and percentage fat mass (2). Changes in serum leptin concentrations are also correlated with changes in weight and adiposity (3). Immunoreactive leptin has been detected in human infant cord blood (14, 15). Leptin concentrations in newborn are independent of maternal levels, therefore cord blood leptin is produced by the placenta and
CLINICAL NUTRITION
159
Table 2 Morphometric indexes at the point of leptin assay and breast milk leptin concentrations of subjects*
Weight (g) Height (cm) BMI of infants (kg/m2) BMI of mothers (kg/m2) Breast milk leptin concentrations (ng/ml)
Obese (n=17)
Non-obese (n=33)
P value
776071141 62.074.7 18.872.8 25.674.1 0.2770.2
63837889 63.9725.9 16.771.4 26.174.6 0.3770.4
0.001 0.578 0.000 0.841 0.984
*mean7SD
Skim milk leptin (ng/mL)
1.0 r = 0.62 P < 0.001 0.8 0.6 0.4 0.2 0.0 15
20
25
30
35
40
BMI (kg/m2) Fig. 2. Relationship between BMI of mothers and breast milk leptin concentrations.
2.0
Skim milk leptin (ng/mL)
r = 0.05 P = 0.72 1.5
1.0
0.5
0 8
10
12
14 16 BMI (kg/m2)
18
20
22
Fig. 3. Relationship between infants’ BMI and breast milk leptin concentrations.
potentially plays a role in fetal and neonatal growth (14–16). Human milk also contains immunoreactive leptin which is identical to intact human leptin (10). Smith– Kirwin et al. showed that human mammary epithelial cells express leptin (13). Leptin concentrations in human milk were correlated with maternal plasma leptin concentrations, but were one order of magnitude lower, maternal body weight, BMI and skinfold thickness which suggested that milk leptin concentrations reflect maternal adiposity (9). Obesity is characterized by an excess of adipose tissue in relation to lean body mass. Standardized definitions
of obesity for infants and children have not been developed. An age- and gender-specific weight-forheight in excess of the 90th percentile on the growth charts or weight in excess of 120% of the median weight for a given height is the traditional definition of obesity (17). Total body fat may be measured directly by hydrostatic weighing or by measuring absorption of gases by lipid tissue or the level of intracellular potassium. Although these methods are impractical in a clinical setting, they form the standards against which indirect methods are evaluated (18). Indirect methods of assessing obesity, including evaluation of the weight– height ratio and calliper measurement of the thickness of skin folds are less precise but less invasive (18). It has been shown that whole-body fat measured by total-body electrical conductivity was strongly correlated with weight-for-length and calf circumference, whereas skinfold thickness, body mass index and Ponderal indexes were poorly correlated with whole-body fat in infants (19). Consequently, we used weight-for-length measurement to define obesity in infants in this study, although it was a rough (but non-invasive) estimation of infant body composition. We showed that leptin concentrations of human milk were not different in obese and non-obese infants’ mothers. Additionally, breast milk leptin concentrations were correlated with maternal BMI but not with infants’ BMI. These findings suggested that milk-borne leptin has no significant effect on adiposity during infancy. These data is consistent with the study of Lo¨nnerdal (20). They reported that serum leptin concentrations were not significantly higher in breast-fed than in formula-fed infants. Thus, it appeared unlikely that leptin in breast milk was absorbed in physiologically relevant amounts, which in turn, would contribute to differences in growth and body composition in infancy (20). It has been showed that leptin concentrations of whole milk were much higher than of skim milk and fat in human milk interfered with the leptin assay. Therefore, we assessed leptin concentrations in skim milk and our results were similar to those in previous studies (13, 20). Although maternal obesity was reported to be associated with increased birth weight previously, we did not find any difference between birth weights and weights at the point of leptin assay of infants whose mothers’ BMIs were equal or superior to 30 into obesity
160
MILK LEPTIN CONCENTRATIONS AND INFANT OBESITY
range and infants whose mothers were not obese (21). This might be due to small number of obese mothers in this study. Human milk contains many hormones and growth factors. It has been proposed that many substances in breast milk may be important for development of the neonatal small intestine or play important roles on immune mechanisms. It is reported that leptin also has a specific effect on T-lymphocyte responses, differentially regulating the proliferation of naı¨ ve and memory Tcells, and increased IL-2 production and IFN-g secretion (22). Recently, leptin receptor was demonstrated to be present on gastric mucous cells and suggested that leptin might has paracrine effect (23). These observations suggest that leptin in breast milk may have different functions related directly to gastrointestinal system or immune system. In summary, breast milk leptin concentrations are not different in mothers of obese and non-obese infants. These findings suggests that milk-borne leptin has no significant effect on adiposity during infancy.
Acknowledgments This research is funded by Milupa.
References 1. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman J M. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425–432 2. Tartaglia L A. The leptin receptor. J Biol Chem 1997; 272(10): 6093–6096 3. Considine R V, Sinha M K, Heiman M L, Kriauciunas A, Stephens T W, Nyce M R, Ohannesian J P, Marco C C, McKee L J, Bauer T L. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Eng J Med 1996; 334: 292–295 4. Nagy T R, Gower B A, Trowbridge C A, Dezenberg C, Shewchuk R M, Goran M I. Effects of gender, ethnicity, body composition, and fat distribution on serum leptin concentrations in children. J Clin Endocrinol Metab 1997; 82: 2148–2152 5. Tang-Christensen M, Havel P J, Jacobs R R, Larsen P J, Cameron J L. Central administration of leptin inhibits food intake and activates the sympathetic nervous system in rhesus macaques. J Clin Endocrinol Metab 1999; 84: 711–717 6. Keim N L, Stern J S, Havel P J. Relationship between circulating leptin concentrations and appetite during a prolonged, moderate energy deficit in women. Am J Clin Nutr 1998; 68: 794–801 7. Senaris R, Garcia-Caballero T, Casabiell X, Gallego R, Castro R, Considine R V, Dieguez C, Casanueva F F. Synthesis of leptin in human placenta. Endocrinology 1997; 138: 4501–4505 Submission date: 6 July 2001 Accepted: 5 November 2001
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