The role of leptin in human growth and puberty

Experimental animal studies demonstrate the effects of leptin on appetite, weight gain and metabolism. The biological effects of leptin in human adults are still to be determined, but recent reports show that congenital leptin deficiency leads to hyperphagia and excessive weight gain from early infancy as well as failure of pubertal onset in adolescence. Our recently reported data from two longitudinal cohorts suggest a role for leptin in the normal regulation of childhood weight gain, maturation and the development of secondary sexual features and body composition. Low leptin levels in cord blood closely reflected decreased adiposity at birth and stringly predicted high rates of weight gain in infancy and cath-up growth. In adolescents, leptin levels rose gradually with age prior to puberty, suggesting that a threshold effect may trigger puberty. In girls, low leptin levels at the start of puberty predicted large gains in the percentage of fat mass, perhaps suggesting a role in the preparation for childbearing.     

The role of leptin in human growth and puberty

Experimental animal studies demonstrate the effects of leptin on appetite, weight gain and metabolism. The biological effects of leptin in human adults are still to be determined, but recent reports show that congenital leptin deficiency leads to hyperphagia and excessive weight gain from early infancy as well as failure of pubertal onset in adolescence. Our recently reported data from two longitudinal cohorts suggest a role for leptin in the normal regulation of childhood weight gain, maturation and the development of secondary sexual features and body composition. Low leptin levels in cord blood closely reflected decreased adiposity at birth and strongly predicted high rates of weight gain in infancy and catch-up growth. In adolescents, leptin levels rose gradually with age prior to puberty, suggesting that a threshold effect may trigger puberty. In girls, low leptin levels at the start of puberty predicted large gains in the percentage of fat mass, perhaps suggesting a role in the preparation for childbearing.     

Variation analysis of β3-adrenergic receptor and melanocortin-4 receptor genes in childhood obesity

BACKGROUND: Decreased energy expenditure and increased food intake are principal causes for obesity. In the present study, genotypes of beta(3)-adrenergic receptor (beta(3)AR) and of melanocortin-4 receptor (MC4R), both of which are believed to have a close link to the cause of obesity, were analyzed and compared with phenotypes of childhood obesity. METHODS: Thirty-five obese children with moderate to severe obesity were enrolled. Direct sequencing of the MC4R coding region and pinpoint-polymerase chain reaction were used to detect genomic variation in the beta(3)AR gene using peripheral blood-derived DNA. RESULTS: Allele frequency of Trp64Arg variation in the beta(3)AR gene in the obese subjects was 0.16, which is comparable with that in the healthy general population in eastern Asia. Comparison of phenotypical characteristics did not show a significant difference between Trp/Trp and Trp/Arg subjects. It was notable that body height SD was significantly higher in the Trp/Trp than the Trp/Arg subjects (0.93 +/- 1.0 SD vs 0.07 +/- 1.3 SD, P= 0.03). Annual weight gains were far beyond a hypothetical fat gain in an Arg64 heterozygote with decreased energy consumption, suggesting increased food intake in childhood obesity. There was, however, no variation in the MC4R gene despite thorough sequencing of the entire coding region. CONCLUSIONS: The Trp64Arg variation in the beta(3)AR gene has no relationship to the degree or the incidence of childhood obesity. The majority of childhood obesity can be characterized as tall stature, more rapid weight gain than that expected by decreased energy expenditure. Further investigation is necessary in regard to the increased food intake as a major cause of childhood obesity.     

Fast-food intake and diet quality in black and white girls: the National Heart, Lung, and Blood Institute Growth and Health Study

OBJECTIVE: To examine trends in fast-food consumption and its relationship to calorie, fat, and sodium intake in black and white adolescent girls. DESIGN: A longitudinal multicenter cohort study of the development of obesity and cardiovascular risk factors in black and white female adolescents. Data collection occurred annually using a validated 3-day food record and a food-patterns questionnaire. SUBJECTS AND SETTINGS: A biracial and socioeconomically diverse group of 2379 black and white girls recruited from 3 centers. MAIN OUTCOME MEASURE: Three-day food records and a food-patterns questionnaire were examined for intake of fast food and its association with nutrient intake. We compared patterns of exposure to fast food and its impact on intake of calories, fat, and sodium. RESULTS: Fast-food intake was positively associated with intake of energy and sodium as well as total fat and saturated fat as a percentage of calories. Fast-food intake increased with increasing age in both races. With increasing consumption of fast food, energy intake increased with an adjusted mean of 1837 kcal for the low fast-food frequency group vs 1966 kcal for the highest fast-food frequency group (P<.05). Total fat in the low fast-food frequency group was 34.3% as opposed to 35.8% in the highest fast-food frequency group (P<.05). Saturated fat went from 12.5% to 13% and sodium increased from 3085 mg to 3236 mg in the lowest vs the highest fast-food frequency group (P<.001). CONCLUSIONS: Dietary intake of fast food is a determinant of diet quality in adolescent girls. Efforts to reduce fast-food consumption may be useful in improving diet and risk for future cardiovascular disease.     

Childhood obesity: trends and potential causes

The increase in childhood obesity over the past several decades, together with the associated health problems and costs, is raising grave concern among health care professionals, policy experts, children's advocates, and parents. Patricia Anderson and Kristin Butcher document trends in children's obesity and examine the possible underlying causes of the obesity epidemic. They begin by reviewing research on energy intake, energy expenditure, and "energy balance," noting that children who eat more "empty calories" and expend fewer calories through physical activity are more likely to be obese than other children. Next they ask what has changed in children's environment over the past three decades to upset this energy balance equation. In particular, they examine changes in the food market, in the built environment, in schools and child care settings, and in the role of parents-paying attention to the timing of these changes. Among the changes that affect children's energy intake are the increasing availability of energy-dense, high-calorie foods and drinks through schools. Changes in the family, particularly an increase in dual-career or single-parent working families, may also have increased demand for food away from home or pre-prepared foods. A host of factors have also contributed to reductions in energy expenditure. In particular, children today seem less likely to walk to school and to be traveling more in cars than they were during the early 1970s, perhaps because of changes in the built environment. Finally, children spend more time viewing television and using computers. Anderson and Butcher find no one factor that has led to increases in children's obesity. Rather, many complementary changes have simultaneously increased children's energy intake and decreased their energy expenditure. The challenge in formulating policies to address children's obesity is to learn how best to change the environment that affects children's energy balance.     

Prevention of childhood obesity

The increasing prevalence of childhood obesity, its attendant morbidity, and the limited success of therapy mandate increased attention to preventive approaches. Environmental and family variables serve to identify families with children at risk for the development of obesity. Although the behavioral correlates that link these risk factors to childhood obesity remain unclear, inactivity and increased dietary intake of fat appear at this time to be the most logical foci for preventive interventions. Television viewing, which promotes both increased food consumption and reduced activity, represents a major concern at which counseling should be directed.     

The global obesity epidemic: snacking and obesity may start with free meals during infant feeding

Feeding is vital for survival. The brain has strong hunger and reward mechanisms that ensure optimal food intake for adequate nutrition. The drive for feeding is particularly strong in humans whose large brains require large energy support. This starts immediately after birth; the newborn child being able to taste sucrose and suck the sweet and fat from its mother's milk. At present, mothers are generally advised to breastfeed children as often as they like, which may be up to 15 times a day. At the same time, childhood obesity is rapidly developing. One reason for the rapidly increasing prevalence of childhood obesity may be overfeeding with snack food.

Conclusion: We hypothesize that non-rule breastfeeding favours the development of snacking throughout the day during childhood, a habit which in turn favours the development of obesity.     

Neuroendocrine regulation of food intake

Seeley RJ, Schwartz MW. Neuroendocrine regulation of food intake. Acta Pædiatr 1999; Suppl 428: 58–61. Stockholm. ISSN 0803–5326
Maintenance of appropriate stores of metabolic fuels depends on carefully matching caloric intake to caloric expenditure. Achieving such'energy balance'is a product of complex interactions of peripheral hormones with effector systems in the central nervous system (CNS) that regulate food intake and energy expenditure. Leptin is a hormone that is made in the adipocytes, circulates in the blood and interacts with receptors in the CNS. These receptors can be found in two different types of systems. One effector system is termed'anabolic'and is activated by low levels of leptin during negative energy balance. This system (exemplified by the hypothalamic neuropeptide Y system) increases food intake and decreases energy expenditure to facilitate the regaining of lost energy stores. The other effector system is termed'catabolic'and is activated by high levels of leptin during positive energy balance. This system (exemplified by the hypothalamic melanocortin and corticotrophin-releasing hormone systems) decreases food intake and increases energy expenditure to facilitate the loss of excess energy stores. Further understanding of these systems is necessary to develop adequate treatments for disorders of energy balance, such as obesity and wasting. □ Corticotrophin-releasing hormone, energy balance, food intake, leptin, melanocortin, neuropeptide Y     

Poor adherence to dietary guidelines among adult survivors of childhood acute lymphoblastic leukemia

Recent studies indicate that survivors of childhood acute lymphoblastic leukemia (ALL) are at increased risk of obesity and cardiovascular disease, conditions that healthy dietary patterns may help ameliorate or prevent. To evaluate the usual dietary intake of adult survivors of childhood ALL, food frequency questionnaire data were collected from 72 participants, and compared with the 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention recommendations, the Dietary Approaches to Stop Hypertension (DASH) diet, and the 2005 United States Department of Agriculture (USDA) Food Guide. Mean daily energy intake was consistent with estimated requirements; however, mean body mass index was 27.1 kg/m2 (overweight). Dietary index scores averaged fewer than half the possible number of points on all 3 scales, indicating poor adherence to recommended guidelines. No study participant reported complete adherence to any set of guidelines. Although half the participants met minimal daily goals for 5 servings of fruits and vegetables (WCRF/AICR recommendations) and 相似文献   

Leptin reduces body weight gain in neonatal rats

Leptin (OB protein) elicits a neuroendocrine response to starvation and states of nutritional abundance to stabilize the proportion of body fat. Leptin has dramatic effects on food intake and energy expenditure in adult and juvenile rodents. However, whether the neonatal period is associated with the development of an effective leptin feedback system is still not known. In this study, we evaluated the effects of peripherally administered leptin on body weight changes in neonatal rats during the early suckling period (from birth to 10 d). Our results show that daily i.p. injections of leptin (0.3 microg/g and 1.0 microg/g) to neonatal rats led to a significant reduction in weight gain over 10 d compared with the control group (p < 0.01 and p < 0.01, respectively). Concomitant with a reduction in weight gain, retroperitoneal fat pad weight also significantly decreased in the leptin-treated group. Our data indicate that the potential for energy balance regulation by leptin occurs in the first day after birth. In addition, we also observed that 3 d after discontinuing leptin treatment, the body weight as well as the fat pad weight of leptin-treated pups returned to the control level. Our results demonstrate that leptin reduces body weight gain in neonatal rats.     

Nutritive Einflussfaktoren auf die Entwicklung von kindlicher Adipositas und mögliche Präventionsansätze

Tremendous increases in the prevalence rates of overweight and obesity in children and adolescents require a search for possible causes and potential prevention strategies. Intrauterine and early infant nutrition are recognized as modifying factors for the development of obesity in adolescence and adulthood. Several recent investigations found that breastfeeding prevents obesity and overweight in later childhood and adolescence. However, so far no causal and definitive factors for the preventive effect could be found.Excessive fat intake during infancy and childhood is thought to play a major role in development of obesity. Typical food preferences for fatty and sweet foods paired with permanent availability and increasing inactivity predispose our society to weight gain and obesity. Preventive measures will have to take into account all possible causative factors in order to fight the disastrous consequences for the whole society.     

Neuroendocrine regulation of food intake

Maintenance of appropriate stores of metabolic fuels depends on carefully matching caloric intake to caloric expenditure. Achieving such 'energy balance' is a product of complex interactions of peripheral hormones with effector systems in the central nervous system (CNS) that regulate food intake and energy expenditure. Leptin is a hormone that is made in the adipocytes, circulates in the blood and interacts with receptors in the CNS. These receptors can be found in two different types of systems. One effector system is termed 'anabolic' and is activated by low levels of leptin during negative energy balance. This system (exemplified by the hypothalamic neuropeptide Y system) increases food intake and decreases energy expenditure to facilitate the regaining of lost energy stores. The other effector system is termed 'catabolic' and is activated by high levels of leptin during positive energy balance. This system (exemplified by the hypothalamic melanocortin and corticotrophin-releasing hormone systems) decreases food intake and increases energy expenditure to facilitate the loss of excess energy stores. Further understanding of these systems is necessary to develop adequate treatments for disorders of energy balance, such as obesity and wasting.     

Is overweight at 12 months associated with differences in eating behaviour or dietary intake among children selected for inappropriate bottle use?

Bottle feeding beyond the recommended weaning age of 12 months is a risk factor for childhood obesity. This paper describes a sample of toddlers at high risk for obesity: prolonged bottle users from a low‐income multi‐ethnic community. We report here baseline mealtime and feeding behaviour, 24 h dietary recall and bottle intake data for Feeding Young Children Study (FYCS) participants, by overweight (≥85% weight‐for‐length) status. FYCS enrolled 12–13‐month‐olds from urban nutrition programmes for low‐income families in the United States who were consuming ≥2 bottles per day. Our sample was predominately Hispanic (62%), 44% of mothers were born outside of the United States and 48% were male. Overall, 35% were overweight. Overweight status was not associated with mealtime/feeding behaviours, bottle use or dietary intake. Most (90%) children ate enough, were easily satisfied and did not exhibit negative (e.g. crying, screaming) mealtime behaviours, per parent report. The sample's median consumption of 4 bottles per day accounted for 50% of their total calories; each bottle averaged 7 ounces and contained 120 calories. Mean daily energy intake, 1098.3 kcal day^?1 (standard deviation = 346.1), did not differ by weight status, nor did intake of fat, saturated fat, protein or carbohydrates. Whole milk intake, primarily consumed via bottles, did not differ by weight status. Thus, overweight 12–13‐month‐olds in FYCS were remarkably similar to their non‐overweight peers in terms of several obesity risk factors. Findings lend support to the set‐point theory and prior work finding that weight and intake patterns in the first year of life alter subsequent obesity risk.     

Leptin: obesity, diabetes and other peripheral effects--a review

Abstract: There is an increasing epidemic of obesity in the Western and developing world that has not spared children and, hence, is of great concern. Obesity presents numerous physiological and psychosocial problems for the child. Childhood obesity not only increases the risk of obesity in adulthood, it is associated with type 2 diabetes mellitus; is the leading cause of pediatric hypertension; increases the risk of coronary heart disease; and increases stress on the weight-bearing joints. Social and psychological problems are also significant consequences of obesity in children, with lowering of self-esteem and its effects on relationships with peers. Obesity is clearly associated with increased levels of the recently discovered hormone, leptin. Leptin, secreted from adipocytes, is involved in the regulation of food intake, energy expenditure, and energy balance in humans. This review focuses on the hormone, leptin, in an effort to document some of its many local and systemic effects on the body and, specifically, its potential role in obesity-induced diabetes.     

Pediatric obesity: etiology and treatment

This article reviews factors that contribute to excessive weight gain in children and outlines current knowledge regarding approaches for treating pediatric obesity. Most of the known genetic causes of obesity primarily increase energy intake. Genes regulating the leptin signaling pathway are particularly important for human energy homeostasis. Obesity is a chronic disorder that requires long-term strategies for management. The foundation for all treatments for pediatric obesity remains restriction of energy intake with lifestyle modification. There are few long-term studies of pharmacotherapeutic interventions for pediatric obesity. Bariatric surgical approaches are the most efficacious treatment but, because of their potential risks, are reserved for those with the most significant complications of obesity.     

International epidemic of childhood obesity and television viewing

Childhood obesity is one of the most serious global public health challenges of the 21st century. The prevalence of this problem has increased at an alarming rate in many countries. The main causes of childhood obesity are; sedentary lifestyle, unhealthy eating patterns, genetic factors, socio-economic status, race/ethnicity, media and marketing, and the physical environment. Children are clearly being targeted as a receptive market by the manufacturing industry. Undoubtedly, television provides one of the most powerful media through which products can be advertised. Furthermore, food advertising accounted for the largest percentage of these advertisements in virtually all countries. Detailed nutritional analysis of food advertisements identified that up to 90% of food products have a high fat, sugar or salt content. Therefore TV viewing is recently identified as one of the risk factors contributing to development of childhood obesity by several mechanisms. This review provides some facts and figures about the global trend of rising obesity among children, amount and content of television and especially food advertisements being watched by children and its possible mechanisms how to cause adverse effects on children's health and contribute to childhood obesity.     

The 'skinny' on childhood obesity: how our western environment starves kids' brains

In this review, the mechanism of our "toxic environment's" effects on insulin and weight gain in the genesis of obesity is elaborated. The composition of our diet is highly insulinogenic. The insulin drives energy into fat, and interferes with leptin signaling in the VMH. This results in weight gain and the sense of starvation, which results in decreased SNS activity, reducing energy expenditure and physical activity; and increased vagal activity, which promotes yet further insulin release and energy storage. Thus, hyperinsulinemia turns the leptin negative feedback system into a "vicious cycle" of obesity (see Figure 3, page 905). Externally, this appears as "gluttony and sloth" but it is biochemically driven. How does this work? A thin, insulin-sensitive, 13-year-old boy might consume a daily allotment of 2,000 kcal, and burn 2,000 kcal daily (or 50 kcal/kg fat-free mass) in order to remain weight-stable, with a stable leptin level. However, if that same 13-year-old became hyperinsulinemic and/or insulin resistant, perhaps as many as 250 kcal of the daily allotment would be shunted to storage in adipose tissue, promoting a persistent obligate weight gain. Due to the obligate energy storage, he now only has 1,750 kcal per day to burn. The hyperinsulinemia also results in a lower level of leptin signal transduction, conveying a CNS signal of energy insufficiency. The remaining calories available are lower than his energy expenditure; the CNS would sense starvation. Through decreased SNS tone, he would reduce his physical activity, resulting in decreased quality of life; and through increased vagal tone, he would increase caloric intake and insulin secretion, but now at a much higher level. Thus, the vicious cycle of gluttony, sloth, and obesity is promulgated. Is this personal responsibility, when a kid's brain thinks it's starving? Is it personal responsibility when the American Academy of Pediatrics still recommends juice for toddlers? Is it personal responsibility when the Women, Infant and Children program subsidizes fruit juice but not fruit? Is it personal responsibility when the first ingredient in the barbecue sauce is high-fructose corn syrup? Is it personal responsibility when high-fiber fresh produce is unavailable in poor neighborhoods? Is it personal responsibility when the local fast food restaurant is the only neighborhood venue that is clean and air-conditioned? Is it personal responsibility when in order to meet the criteria for No Child Left Behind, the school does away with physical education class? Is it personal responsibility when children are not allowed out of the house to play for fear of crime? We must get the insulin down. Fixing the "toxic environment" by altering the food supply and promoting physical activity for all children can't be done by government, and won't be done by Big Food. This will require a grassroots, bottom-up effort on the part of parents and community leaders. We as pediatricians must lead the way.     

Television and children's consumption patterns. A review of the literature

The recent increase in childhood obesity has, among other things, focused attention on the role that television may play. This paper summarizes results of studies published in peer review journals since 1970 with data pertaining to the relationship between television use and children's food intake. Studies fall into four categories: content analyses; effects of television advertising on children's food behaviors; television and pediatric obesity, with effects on children's dietary intake and physical activity; and television use and children's food consumption patterns. Content analyses have shown that food is the most frequently advertised product category on children's TV. The majority of these ads target highly sweetened products, but more recently, the proportion from fast food meal promotions has been growing. Controlled studies on children's choices have consistently shown that children exposed to advertising choose advertised food products at significantly higher rates than do those not exposed. Purchase request studies have documented associations between number of hours of TV watched and number of requests from the child to the mother for specific food items, as well as the presence of those items in the home. Greater TV use has been associated with higher intakes of energy, fat, sweet and salty snacks, and carbonated beverages and lower intakes of fruit and vegetables. Several large studies have documented associations between number of hours of TV watched and both the prevalence and incidence of obesity. The combination of lifestyle factors that accompany heavy television use appear to place children at risk of obesity and poor nutritional status.     

Application of DEXA in body composition assessment in children

Clinical and research applications of dual-energy X-ray absorptiometry in childhood are reviewed. Originally used for bone mineralization assessment in adults with osteoporosis, total body dual-energy X-ray absorptiometry is now also used currently alone or combined with other techniques for assessment of fat mass and fat-free mass. Low invasiveness, accuracy, swiftness and availability of pediatric software make total-body dual-energy X-ray absorptiometry suitable for studying body composition in a wide variety of metabolic and nutritional disorders in childhood such as simple or genetic obesity, insulin-dependent diabetes mellitus, congenital hypothyroidism, celiac disease, asthma, growth hormone deficiency and cachexic states.     

Risk factors for childhood overweight

PURPOSE OF REVIEW: We review the 2004 literature on risk factors for childhood overweight. Given the steady increase in the prevalence of childhood overweight, the identification of risk factors is of increasing importance. RECENT FINDINGS: A number of studies confirmed that parental overweight is the most potent risk factor for childhood overweight. Childhood temperament was found to mediate the effects of parental overweight with a difficult temperament increasing the risk of overweight. Newer findings implicate regular consumption of fast food and sweetened drinks as risk factors, as well as sedentary behavior; although a meta-analysis suggested that the effects of the latter factor are small. Other work was consistent with the finding that parental overcontrol of children's feeding behavior, particularly for those at high risk of developing overweight, may lead to overweight. SUMMARY: Identification of groups of children at high risk for becoming overweight offers the potential for early intervention to reduce the intergenerational transfer of obesity. This is an area for future research because the nature of effective intervention is at present unclear. There is a suggestion that focused behavior change efforts on one target such as reducing the intake of sweetened beverages may be more successful than attempts to make broader dietary changes. There is also evidence that targeting parental behaviors may be more effective than interventions directed solely toward children, suggesting that modification of the environment that a child is exposed to during early development may have a lasting effect.