A physiological role of breast milk leptin in body weight control in developing infants.

Objective: Leptin, a hormone that regulates food intake and energy metabolism, is present in breast milk. The aim of this study was to determine whether milk leptin concentration is correlated with maternal circulating leptin and BMI and with body weight gain of infants.

Research Methods And Procedures: A group of 28 non-obese women (BMI between 16.

Remodeling of white adipose tissue after retinoic acid administration in mice.

A reduced brown adipose phenotype in white adipose tissue (WAT) may contribute to obesity and type 2 diabetes in humans. Retinoic acid, the carboxylic form of vitamin A, triggers in rodents a reduction of body weight and adiposity and an increased expression of uncoupling proteins in brown adipose tissue and skeletal muscle. In this study, we investigated possible remodeling effects of all-trans retinoic acid (ATRA) in WAT depots.

Understanding and preventing childhood obesity and related disorders--IDEFICS: a European multilevel epidemiological approach.

The environment of children has drastically changed in Europe during the last decades as reflected in unhealthy dietary habits and sedentary lifestyle. Nutrition obviously plays a part in the development of overweight in childhood. However, dietary factors and physical activity are also involved in the development of metabolic syndrome, type II diabetes, cardiovascular diseases, osteoporosis, and postural deformities like scoliosis, effects related in part to excessive weight gain.

Resistin as a putative modulator of insulin action in the daily feeding/fasting rhythm.

Resistin and adiponectin are adipokines with postulated opposite functions. Resistin has been related with insulin resistance in obesity, while adiponectin could be associated to higher insulin sensitivity. We have determined whether the production of these two adipokines during the day is related to the feeding rhythm in rats.

Effects of retinoic acid administration and dietary vitamin A supplementation on leptin expression in mice: lack of correlation with changes of adipose tissue mass and food intake.

Retinoic acid (RA) administration and chronic vitamin A supplementation were reported to inhibit adipose tissue leptin expression in rodents, but the impact of this effect on food intake and its relationship with changes of body adiposity was not analyzed. Here, we have studied the effects of RA administration at three different doses on body weight, adipose tissue mass, food intake, adipose tissue leptin expression and circulating leptin levels in NMRI mice; the effects of chronic vitamin A supplementation with a 40-fold excess retinyl palmitate on the same parameters in NMRI and C57BL/6J mice; and the effects of RA and retinoid receptors agonists on leptin expression in brown and white adipocyte cell model systems. The results show that vitamin A down-regulates leptin expression in white and brown adipose tissue and circulating leptin levels independently of changes of adipose tissue mass and, for the first time to our knowledge, that this effect does not correlate with increased food intake.

Retinoic acid modulates the retinoblastoma protein during adipocyte terminal differentiation.

Terminal differentiation is characterized by a permanent withdrawal of cells from the cell cycle. Retinoblastoma protein (RB) has been involved in cell cycle progression. Accumulating evidence also implicates RB in the promotion of differentiation of many cell types.

Beta-carotene and the application of transcriptomics in risk-benefit evaluation of natural dietary components.

Beta-carotene is a natural food component that is present in fruits and vegetables and is also used as a food colorant and a supplement. Beta-carotene is an anti-oxidant and a source of vitamin A. It is endowed with health beneficial properties, but a number of studies showed that with high intakes it may increase the risk for lung cancer in at risk individuals (heavy smokers, asbestos workers and alcohol users).

Beta-carotene uptake and metabolism in human lung bronchial epithelial cultured cells depending on delivery vehicle.

Beta-carotene (BC) could have a protective or pro-carcinogenic role in lung cancer, and cell culture systems are important to evaluate it. Nevertheless, the delivery of the hydrophobic BC to cells is difficult. Different vehicles have been used such as liposomes, tetrahydrofuran and serum lipoproteins, but presenting different problems.

Morphology of ferret subcutaneous adipose tissue after 6-month daily supplementation with oral beta-carotene.

Adipose tissue is an important retinoid depot and retinoids are known to influence white and brown adipocyte metabolism. Identifying nutrients that can affect the biological activity of the adipose organ would be of great medical interest in the light of the current obesity epidemic and related disorders in developed countries. The vast majority of mammal studies of chronic administration of oral beta-carotene have used murine models, while few have employed mammals exhibiting uptake and processing of intestinal beta-carotene similar to those of humans.

Leptin orally supplied to neonate rats is directly uptaken by the immature stomach and may regulate short-term feeding.

Although leptin is a hormone mainly produced by the adipose tissue, it is also produced by the gastric mucosa and the mammary epithelium and is present in maternal milk. The effects of milk leptin on the neonate are not known. The purpose of the investigation was to evaluate the short-term effects of the administration of a single oral dose of leptin on 4-d-old rats as well as the effects of chronic supplementation during the lactation period with a daily oral dose of leptin (equivalent to 5 times the amount of leptin ingested normally from maternal milk during the suckling period) on body weight, the gastric leptin system, gastric food content, and thermogenic capacity.

Retinoic acid administration and vitamin A status modulate retinoid X receptor alpha and retinoic acid receptor alpha levels in mouse brown adipose tissue.

Background/aims: Retinoic acid (RA), the carboxylic acid form of vitamin A, through the activation of cognate receptors, stimulates the transcription of the gene encoding uncoupling protein 1 (UCP1), which is critical to brown adipose tissue (BAT) thermogenesis. RA was previously shown to down-regulate the steady state levels of retinoic acid receptor alpha (RARalpha) and retinoid X receptor alpha (RXRalpha) in primary brown adipocytes differentiated in culture. Our aim was to study the impact of RA-treatment and vitamin A status on the expression levels of these receptors in vivo.

Effects of fasting on lipoprotein lipase activity in different depots of white and brown adipose tissues in diet-induced overweight rats.

The aim of the present study was to evaluate the effects of 24 hours of starvation on lipoprotein lipase (LPL) activity in various depots of white and brown adipose tissues in control rats and in rats with two different degrees of overweight, both induced by dietary treatment. In control rats, no changes in LPL immunoreactive mass were observed in either white or brown adipose tissues after fasting, whereas the effects of food deprivation on enzyme activity were opposite in white versus brown adipose tissues. The LPL activity response to fasting was impaired by obesity: White adipose depots of cafeteria obese rats showed a lower ability to downregulate LPL during fasting and the increased LPL activity induced by fasting in brown adipose depots was less intense in the obese rats compared with control animals.

The Arg64 allele of the beta 3-adrenoceptor gene but not the -3826G allele of the uncoupling protein 1 gene is associated with increased leptin levels in the Spanish population.

To determine whether there are variations in leptin levels according to the beta(3)-adrenoceptor (beta(3)-AR) Trp64Arg and uncoupling protein 1 (UCP1) -3826A-->G polymorphisms, given the regulatory role of catecholamines through the beta(3)-AR in leptin production and the previously reported association of the UCP1 -3826A-->G variant with obesity. A total of 160 men and 172 women randomly chosen from a nationwide population-based obesity cross-sectional survey in Spain were studied. Body mass index (BMI), waist-to-hip ratio (WHR), leptin, insulin, fasting and 2-hour post-glucose load glycemia, high-density lipoprotein (HDL)-, low-density lipoprotein (LDL)-, and total cholesterol, and triglyceride plasma levels were measured.

PPAR-gamma2 expression in response to cafeteria diet: gender- and depot-specific effects.

Objective: To investigate the effects of short-term cafeteria (CAF) diet feeding on the expression of adipogenic transcription factors and their association with adiposity.

Research Methods And Procedures: Four-week-old male and female Wistar rats were fed CAF diet or standard chow for 2 weeks. Body weight, energy intake, tissue weights, and serum parameters were determined.

Food safety and functional foods in the European Union: obesity as a paradigmatic example for novel food development.

Since 1997, the European Union has undergone deep changes in the scientific assessment of food-related problems. Among the immediate challenges in the near future are the scientific and technological developments and regulatory measures for the so-called "functional foods," which can positively affect the health and well- being of consumers. Obesity, whose genetic and molecular basis are increasingly understood, is now foreseen as one of the key targets for novel functional foods developments, and offers a paradigmatic example of the complexity of a biological system as a target to be controlled.

[Nutrigenomics and obesity].

Obesity is a multifactorial disorder affected by multiple genetic and environmental factors, in particular nutrients, and their interrelationships. Increasing knowledge of the genes and molecules involved in the development of obesity is paving the way for new methods of obesity control. In this sense, Nutrigenomics--which represents a new approach in nutrition research that joints the application of powerful functional genomics technologies, bioinformatics and molecular biology with more traditional methodologies--may orientate the design and development of new functional foods for obesity, based on the scientific knowledge of the impact of specific nutrients on the mammalian body weight control system and their mechanisms of action.

The steroid RU486 induces UCP1 expression in brown adipocytes.

RU486 (mifepristone), a potent antagonist at progesterone and glucocorticoid receptors (PR and GR), is well known for its use in the termination of unwanted pregnancies, the potential development of oral contraceptives, treatment of certain cancers and other activities. Potentially, it could also play a role in obesity control, although the few studies that have addressed this aspect have focused mainly on its central and anti-glucocorticoid effects. We have shown previously that it could have a direct effect on brown adipocytes in culture when administered together with progesterone.

The inhibition of gastric ghrelin production by food intake in rats is dependent on the type of macronutrient.

Ghrelin is a peptide mainly produced by the stomach that increases food intake and body weight. Ghrelin expression increases with fasting and is diminished by re-feeding, but although the expression of this hormone is regulated by the feeding state, the relation with diet composition is not yet well established. We have studied the inhibitory effect of the intake of two different macronutrients (fat and carbohydrates) on ghrelin production by the stomach in fasted rats, as well as the relation with another important signal in the regulation of energy balance, leptin.

Diurnal rhythms of leptin and ghrelin in the systemic circulation and in the gastric mucosa are related to food intake in rats.

We investigated diurnal changes in leptin and ghrelin levels in the stomach and in the systemic circulation and their relation to food intake rhythms in Wistar rats housed at 22 degrees C with a 12-h light/dark cycle and free access to food and water. Animals were sacrificed every 3 h over a 24-h period. Leptin and ghrelin levels in serum and in the gastric mucosa were analysed by immunoassay.

Modulation of resistin expression by retinoic acid and vitamin A status.

This work identifies retinoic acid (RA), the acid form of vitamin A, as a signal that inhibits the expression of resistin, an adipocyte-secreted protein previously proposed to act as an inhibitor of adipocyte differentiation and as a systemic insulin resistance factor. Both 9-cis and all-trans RA reduced resistin mRNA levels in white and brown adipocyte cell model systems; the effect was time- and dose-dependent, was followed by a reduced secretion of resistin, and was reproduced by selective agonists of both RA receptors and rexinoid receptors. Association of CCAAT/enhancer-binding protein alpha (a positive regulator of the resistin gene) and its coactivators p300, cAMP response element-binding protein binding protein, and retinoblastoma protein with the resistin gene promoter was reduced in RA-treated adipocytes.

Uncoupling proteins: gender dependence and their relation to body weight control.

Members of the uncoupling protein (UCP) family have different purported functions, which can be either directly or indirectly related to the control of body weight. In this sense, most studies on this topic have been carried out using male subjects, although different works with males and females have shown important sex-associated differences in the regulation of these proteins; for instance, sex differences have been shown in the cold-, diet- and overweight-induced expression of brown adipose tissue UCP1 and also in the correlation of muscle UCP3 with overweight. In these kinds of studies, models of obesity such as cafeteria diet feeding and postcafeteria have been very useful.

Uncoupling proteins: gender-dependence and their relation to body weight control.

The members of the uncoupling protein family have different purported functions, which can be either directly or indirectly related to the control of body weight. In this sense, a great part of the studies carried out on this topic have been made using male subjects, although different works with male and female subjects have shown important sex-associated differences in the regulation of these proteins; for instance, sex differences have been shown in the cold-, diet- and overweight-induced expression of brown adipose tissue UCP1 and also in the correlation of muscle UCP3 with overweight. In these kinds of studies, models of obesity such as the cafeteria diet feeding and postcafeteria have been very useful.

Resistin expression in different adipose tissue depots during rat development.

Resistin is a hormonal factor synthesised by adipocytes that was first thought to be related with the resistance to insulin in obesity, but whose function is not yet completely established. Here we have studied the ontogenic pattern of resistin mRNA expression in different white adipose tissue depots (WAT)--epididymal, inguinal, mesenteric and retroperitoneal--and in brown adipose tissue (BAT), as well as the circulating resistin levels, in rats of different ages (from the suckling period to one year of age). Resistin mRNA was determined by Northern blotting, and serum levels by enzyme immunoassay.

The glutamine 27 glutamic acid polymorphism of the beta2-adrenoceptor gene is associated with abdominal obesity and greater risk of impaired glucose tolerance in men but not in women: a population-based study in Spain.

Objective: Given the important role of the beta2-adrenoceptor (beta2-AR) in lipid mobilization and the lack of studies in Southern European countries, the aim of this study was to investigate the role of the glutamine 27 glutamic acid (Gln27Glu) beta2-AR polymorphism in the susceptibility to obesity and its metabolic complications in a population-based nationwide multicentre study in Spain, especially focusing on the hypothetical influence of gender.

Design: Cross-sectional population-based study.

Patients: We studied 666 nonrelated adults (47.