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Biomedical subjects

Catalina Picó

Publications and source records attributed to Catalina Picó.

15 recordsLinked to original sources

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 16.3 and 27.3 kg/m(2)) who breast-fed their infants for at least 6 months and their infants were studied. Venous blood and milk samples were obtained from mothers at 1, 3, 6, and 9 months of lactation, and leptin concentration was determined. Infant body weight and height were followed until 2 years of age. RESULTS: During the whole lactation period, milk leptin concentration correlated positively with maternal plasma leptin concentration and with maternal BMI. In addition, milk leptin concentration at 1 month of lactation was negatively correlated with infant BMI at 18 and 24 months of age. A better negative correlation was also found between log milk leptin concentration at 1 and at 3 months of lactation and infant BMI from 12 to 24 months of age. DISCUSSION: We concluded that, in a group of non-obese mothers, infant body weight during the first 2 years may be influenced by milk leptin concentration during the first stages of lactation. Thus, moderate milk-borne maternal leptin appears to provide moderate protection to infants from an excess of weight gain. These results seem to point out that milk leptin is an important factor that could explain, at least partially, the major risk of obesity of formula-fed infants with respect to breast-fed infants.

Adult↗

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. Our results show that the administration of a single oral dose of 4 ng of leptin to 4-d-old rats produces a short-term increase in leptin levels in the stomach and serum and a decrease in the weight of the gastric contents. Pups treated with a daily oral dose of leptin during the whole lactation period showed, at the end of the suckling period, compared with controls, lower gastric contents, lower leptin production by the stomach and the sc adipose tissue, and lower thermogenic capacity in brown adipose tissue. We conclude that oral leptin is absorbed by the immature gastric epithelium of the neonate, and this leptin exerts clear biological effects, down-regulating endogenous leptin production and playing a potential role in the short-term control on food intake during the lactation period.

Administration, Oral↗

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. While rodents transform practically all ingested beta-carotene into retinol, in ferrets, as in humans, part of the beta-carotene is absorbed and released into the circulation intact. We studied the effects of 6-month daily administration of two doses of oral beta-carotene (0.8 or 3.2 mg/kg/day) on ferret body weight, size of body fat depots, and, using morphological and morphometric methods, on subcutaneous (inguinal) white adipose tissue (WAT). Because of the oral mode of administration, liver, stomach, and small and large intestine were also studied. Control animals received the vehicle. Data show that at the end of treatment the higher dose induced significantly higher body weight compared with controls and significantly higher inguinal fat depot compared with animals treated with the lower dose. In addition, chronic treatment with beta-carotene induced a dose-dependent hypertrophy of white adipocytes and increased neoangiogenesis in subcutaneous WAT in all treated ferrets. Vasculogenesis was independent of adipocyte hypertrophy. We also found focally evident liver steatosis in the ferrets treated with the higher dose of beta-carotene. The other gastrointestinal tract organs studied were not significantly different from those of control animals.

Adipose Tissue↗

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. Ghrelin mRNA expression in the gastric mucosa was determined by Northern blotting, and leptin mRNA expression was determined by Northern blotting in the adipose tissue and by RT-PCR in the stomach; circulating and gastric concentrations of ghrelin and leptin were measured by enzyme immunosorbent assay and ELISA, respectively. Our results showed an increase in ghrelin mRNA levels in response to 14 h of fasting. Food intake for 20 min after the fast produced a decrease in ghrelin mRNA expression that was recovered in 45 min in rats that ate the fat diet, whereas levels remained low when rats ate the carbohydrate diet. Serum ghrelin followed a similar tendency. The decrease in ghrelin expression by feeding was associated with an increased expression of gastric leptin only when animals ate carbohydrates. We conclude that the inhibition of ghrelin production by the stomach after re-feeding of fasted rats is dependent on diet composition and can be related to the different satiating capacity of the ingested macronutrients, which is higher for carbohydrates than fat.

Adipose Tissue↗

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. Leptin mRNA levels were determined in the gastric mucosa by RT-PCR and in different adipose tissue depots (epididymal, retroperitoneal and mesenteric) by Northern blot. Ghrelin mRNA levels were determined by Northern blot. Gastric and serum leptin levels displayed similar diurnal rhythms, rising during the dark phase and decreasing gradually during the light phase. Leptin expression in the different adipose tissue depots correlated positively with circulating leptin levels ( P<0.05), although there were some depot-associated differences. Leptin mRNA levels in the mesenteric depot correlated positively with food intake ( P<0.05). In blood, ghrelin levels rose sharply just before the onset of the dark phase and dropped suddenly just after. In the stomach, ghrelin levels were high during the fasting period of light and low during the night, and correlated inversely with food intake, gastric contents and serum leptin levels ( P<0.05). Leptin and ghrelin in the stomach and in the systemic circulation thus show diurnal variations that are influenced by food intake rhythms. The results agree with a role for ghrelin as a stimulant of meal initiation.

Animals↗

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.

Consumer Product Safety↗

Positive correlation of skeletal muscle UCP3 mRNA levels with overweight in male, but not in female, rats.

The objective of this study was to investigate the sex-dependent regulation of skeletal muscle uncoupling protein (UCP)3 mRNA expression in response to overweight and its relationship with serum levels of free fatty acids, leptin, and insulin. Two obesity models were used: rats made obese by feeding them with a cafeteria diet for 14 wk, and postcafeteria overweight rats fed a chow diet for 10 wk after consuming the cafeteria diet for 14 wk. The effects of 24-h fasting were studied in postcafeteria rats and their age-matched controls. The cafeteria rats ate a high-fat diet and attained an excess body weight that was higher in females (+59%) than in males (+39%). A trend to higher induction of abdominal muscle UCP3 mRNA in male rats than in females after cafeteria diet was apparent (+116% increase vs. +26% increase). Postcafeteria male but not female rats still showed the tendency to have increased UCP3 mRNA levels relative to their age-matched controls. A linear regression analysis showed a significant positive correlation of the UCP3 mRNA levels with overweight and with serum levels of leptin and insulin in males, but not in females, and no correlation with serum free fatty acid levels. A subsequent correlation analysis and a multiple linear regression analysis showed that overweight was the only parameter actually related to UCP3 mRNA levels in males. Fasting-induced upregulation of muscle UCP3 mRNA levels was higher in males (5- to 7-fold) than in females (3- to 4-fold). Our results point to the existence of sex-associated differences in the control of muscle UCP3 expression in response to overweight and fasting, with an impaired induction in female rats under both conditions. The correlation of abdominal muscle UCP3 mRNA expression with overweight in males could be related to their relative resistance to gain weight after chronic overeating of a cafeteria diet, by the purported role of UCP3 in the regulation of lipid utilization.

Animal Feed↗

Blood leptin homeostasis: sex-associated differences in circulating leptin levels in rats are independent of tissue leptin expression.

Circulating leptin levels are higher in women than in men. The aim of the study has been to determine in rats the putative existence of sex-associated differences in leptin expression in different adipose tissue depots (gonadal, retroperitoneal, mesenteric and inguinal white adipose tissue and interscapular brown adipose tissue) and the relationship with circulating leptin levels. Adult male and female Wistar rats acclimated to 22 degrees C or to 28 degrees C were used. Leptin mRNA expression was assessed by northern blot and serum leptin levels by enzyme-linked immunosorbent assay (ELISA). Contrary to what happens in humans, we report here that male rats acclimated to standard animal house conditions (22 degrees C) have a higher leptin concentration in blood than female rats. This situation cannot be explained by a greater size of the fat depots in males, because the adiposity index is similar in both genders, but are rather associated to higher leptin specific mRNA expression by the white adipose tissue. Around thermoneutral conditions (28 degrees C), sex related differences in leptin mRNA expression disappear, but the gender difference in circulating leptin levels remains. In addition, leptin mRNA expression is higher in both genders in thermoneutral conditions but this is not reflected in changes in the circulating leptin levels. In conclusion, this study shows that rat circulating leptin levels are finely regulated, and not exclusively dependent on leptin mRNA expression, but other mechanisms are also involved, possibly regarding leptin rate of degradation.

Adipose Tissue↗

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. In WAT, resistin expression remains almost constant with age, except in early development, where there is a peak of expression in the epididymal and retroperitoneal depots, and a decrease in the inguinal one, while the expression remains constant for the mesenteric depot. Moreover, there is a site-specific difference regarding resistin expression: all the depots express characteristic levels of mRNA, especially at the age of 2 months, the moment when resistin mRNA levels are significantly higher in the epididymal and the retroperitoneal than in the inguinal and mesenteric WAT and than in the BAT. The transient increased resistin expression in the epididymal and the retroperitoneal WAT at a period of time in which there is a change in diet (from milk to chow) suggests a common nutritional regulation of the resistin gene. Circulating resistin levels increase with age probably reflecting the increase in the body fat content.

Adipose Tissue↗

Gastric leptin: a putative role in the short-term regulation of food intake.

The discovery of the production of leptin by the stomach, in addition to its production by adipose tissue, has initiated new investigation into the possible role of this protein in the digestive physiology, in particular in the short-term control of energy balance. Leptin has been identified in the lower half of the stomach glands both in the pepsinogen granules of chief cells and in the granules of a specific endocrine cell type, suggesting that leptin action is exerted by both exocrine and endocrine pathways. Gastric leptin is sensitive to the nutritional state, being rapidly mobilized in response to food intake following fasting, or after the administration of satiety factors; this suggests a role for this protein in the short-term regulation of feeding, acting in collaboration with satiety peptides such as cholecystokinin. Leptin, produced by gastric cells and by adipocytes, could act on both acute and chronic regulation of feeding behaviour respectively, giving information to the brain on the availability of external (food) and internal (fat depots) energy resources, thus participating in short- and long-term satiation.

Adipose Tissue↗

Perinatal expression of leptin in rat stomach.

It has been reported recently that the stomach can produce and store leptin and release it, both into the blood and into the gastrointestinal lumen, in response to food intake. Here, we have followed the ontogenic pattern of leptin mRNA expression and leptin levels in stomach during the perinatal period, which were compared with adults. Leptin mRNA expression was assessed by reverse transcriptase-polymerase chain reaction, and tissue leptin content by enzyme-linked immunosorbent assay and localised by immunohistochemistry. Leptin mRNA is expressed at low levels in rat stomach in prenatal stages. It increased from 4 to 8 hr of life in suckling rats, an increase not observed in the fasted pups, which were separated from their mothers immediately after birth. Leptin expression rose steadily after birth during the first month of life, with a marked increase from 15-day-old rats, followed by a parallel increase in leptin levels from day 21 of life, which was coincident with the change from suckling to a solid diet. The immunohistochemical analysis showed leptin immunoreactivity at different levels of the stomach mucosa, suggesting that during early development leptin could derive from different sources. During the pre- and neonatal periods, leptin is mainly located at the superficial epithelium (suggesting maternal origin from amniotic cells and mammary glandular cells, respectively). At the beginning of the chow diet, the stomach produces leptin in the glands (main source from 15 days of life), suggesting an endogenous production of the protein after that period. The present work demonstrates the expression of leptin mRNA and leptin protein in the stomach of neonate rats, and shows that the ontogenic profile of leptin appearance in the stomach during the perinatal period is probably related to the onset of suckling and to the change of diet from milk to solid chow.

Animals↗

Leptin production by the stomach is up-regulated in obese (fa/fa) Zucker rats.

OBJECTIVE: Genetically obese (fa/fa) Zucker rats display markedly elevated circulating leptin levels compared with their lean counterparts; this is expected because of the lack of a LepR-mediated feedback inhibition. The aim of this study was to determine the effect of the leptin receptor mutation in the Zucker rat on gastric leptin production and on the response to 14 hours of starvation. The response to a short-term period of food intake (20 minutes) on gastric leptin release was also analyzed. RESEARCH METHODS AND PROCEDURES: Leptin mRNA expression in the gastric mucosa and in adipose tissue depots (epididymal, retroperitoneal, mesenteric, and inguinal) was assessed by reverse transcriptase-polymerase chain reaction and serum and stomach leptin content by enzyme-linked immunosorbent assay. RESULTS: Obese Zucker rats overexpressed leptin in the stomach. They overexpress leptin in the inguinal adipose tissue but not in visceral adipose tissue depots, indicating tissue-specific obesity-dependent differences. Gastric leptin expression is regulated by feeding conditions in lean but not in obese (fa/fa) rats. In lean animals, leptin mRNA levels decrease in fasting conditions and increase rapidly with a short period of food intake. Obese Zucker rats also overdisplay stomach leptin levels. Feeding acutely stimulates leptin secretion by the stomach in lean, and to a lesser extent, in obese rats. DISCUSSION: These results indicate impaired regulation of leptin expression in the stomach of obese (fa/fa) Zucker rats. However, there is still an effect of the nutritional status on gastric leptin levels despite the lack of a functional leptin receptor.

Adipose Tissue↗

Dietary fat source regulates ob gene expression in white adipose tissue of rats under hyperphagic feeding.

This work was designed to investigate the effect of different lipid sources on ob gene expression and serum leptin levels in rats with two different feeding protocols: (1) free access to food; or (2) energy-controlled feeding. Male Wistar rats were fed diets containing 40 % energy as fat (olive oil, sunflower oil or beef tallow), for 4 weeks. In Expt 1 rats had free access to food, and in Expt 2 rats were fed a controlled amount of food (16 g/d, equivalent to 300 kJ/d). Insulin and leptin were determined by ELISA and ob mRNA by Northern blot. When rats had free access to food, ob mRNA levels were higher in animals fed either olive oil or sunflower oil than in those fed beef tallow. In marked contrast with feeding ad libitum, no differences were found among dietary fat groups in rats fed energy-controlled diets. When both feeding protocols were compared, free access to food induced an increased expression of ob mRNA in perirenal and/or epididymal adipose tissues from rats fed either olive oil or sunflower oil, but not from rats fed beef tallow. Dietary lipid type did not induce modifications in serum leptin concentrations. A tendency to higher serum leptin levels was observed more in rats with free access to food than in rats fed energy-controlled feeding. No differences were found in insulin levels. Dietary fat type importantly affects ob mRNA expression in rat white adipose tissue under hyperphagic conditions. Further study is needed in order to elucidate the mechanism underlying this effect.

Adipose Tissue↗

Olive oil feeding up-regulates uncoupling protein genes in rat brown adipose tissue and skeletal muscle.

BACKGROUND: Some nutrients, such as carotenoids, retinoic acid, and certain types of fatty acids, increase thermogenic capacity. OBJECTIVE: The influence of 4 dietary lipid sources (olive oil, sunflower oil, palm oil, and beef tallow) on the content of uncoupling proteins 1, 2, and 3 (UCP1, UCP2, and UCP3) and their messenger RNA (mRNA) expression in several tissues of rats was compared. DESIGN: Wistar rats were randomly divided into 4 groups and fed ad libitum diets containing 40% of energy as fat. UCP1, UCP2, and UCP3 mRNA and protein were assessed by Northern blot and Western blot, respectively. Oxygen consumption in tissues was measured by polarography. Total-body oxygen consumption was assessed in an open-circuit chamber system. Circulating fuels (fatty acids and glucose) and hormones (triiodothyronine, thyroxine, corticosterone, and insulin) were measured. RESULTS: Olive oil feeding induced the highest UCP1, UCP2, and UCP3 mRNA expression in interscapular brown adipose tissue. An analogous effect was observed in gastrocnemius muscle UCP3 mRNA. No significant differences were observed in perirenal white adipose tissue UCP2 mRNA. Changes in mRNAs were not accompanied by close changes in the protein content of UCPs and were not associated with changes in adipose tissue oxygen consumption. Nevertheless, total-body oxygen consumption was higher in rats fed olive oil than in those fed the other 3 diets. No significant differences were found in body and tissue weights or in serum indexes. CONCLUSION: Olive oil induced an up-regulating effect on UCP mRNA that was probably not mediated by systemic metabolic changes, but rather related to a local effect on interscapular brown adipose tissue and skeletal muscle.

Adipose Tissue↗