Biomedical subjects

Paula Oliver

Publications and source records attributed to Paula Oliver.

13 recordsLinked to original sources

PubMed2005

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↗

PubMed2004

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↗

PubMed2004

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. We present new insights into the role of RB and other cell cycle regulatory proteins in adipocyte differentiation and on the role of retinoic acid (RA) in the regulation of the latter process. It is shown that RA reduces RB expression and enhances RB phosphorylation by a mechanism that involves down-regulation of the cyclin-dependent kinase inhibitor (CKI) p21(Cip1), having this fact as important consequences for both the cell cycle progression and the adipocyte differentiation process. The effects of RA result in the blockage of adipogenesis, but may also favor the retention of a pool of adipose cells able to re-enter the cell cycle, which may be important for the developmental dynamics of adipose tissue in vivo. In addition, these results reinforce the idea that there is a cross-talk between the cell cycle machinery and the adipocyte differentiation machinery that can be modulated by external signals, including nutrients.

3T3 Cells↗

PubMed2004

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↗

PubMed2004

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↗

PubMed2003

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↗

PubMed2003

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↗

PubMed2003

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↗

PubMed2003

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

Targeted disruption of the gene for natriuretic peptide receptor-A worsens hypoxia-induced cardiac hypertrophy.

Targeted disruption of the gene for natriuretic peptide receptor-A (NPR-A) worsens pulmonary hypertension and right ventricular hypertrophy during hypoxia, but its effect on left ventricular mass and systemic pressures is not known. We examined the effect of 3 wk of hypobaric hypoxia (0.5 atm) on right and left ventricular pressure and mass in mice with 2 (wild type), 1, or 0 copies of Npr1, the gene that encodes for NPR-A in mice. Under normoxic conditions, right ventricular peak pressure (RVPP) was greater in 0 than in 2 copy mice, but there were no genotype-related differences in carotid artery PP (CAPP). The left ventricular free wall weight-to-body weight (LV/body wt) ratio was greater in 0 than in 2 copy mice and there was a trend toward a greater right ventricular weight-to-body weight (RV/body wt) ratio. Three weeks of hypoxia increased RVPP and RV/body wt in all genotypes. The increase in RVPP was similar in all genotypes (11-14 mmHg), but the hypoxia-induced increase in RV/body wt was more than twice as great in 0 copy mice than in 2 copy mice (1.11 +/- 0.06 to 2.65 +/- 0.46 vs. 0.96 +/- 0.04 to 1.4 +/- 0.09, P < 0.05). Chronic hypoxia had no effect on CAPP in any genotype and did not effect LV/body wt in 1 or 2 copy mice, but increased LV/body wt 41% in 0 copy mice. We conclude that absent expression of NPR-A worsens right ventricular hypertrophy and causes left ventricular hypertrophy during exposure to chronic hypoxia without increasing pulmonary or systemic arterial pressure responses.

Animals↗

PubMedDate not supplied

Topical photodynamic therapy: an introduction for nurses.

Non-melanoma skin cancers are the most common cancers in the UK. Although an estimated 50000 cases were registered in 1999 across England and Wales, there is likely to be significant under-reporting of cases. However, the cancer registries do not include pre-cancerous lesions of the skin and therefore the number treated will greatly outnumber the cancers (National Institute for Health and Clinical Excellence, 2006). Topical photodynamic therapy (PDT) is one of several effective treatments for pre-malignant and malignant non-pigmented skin cancers. The treatment is non-invasive and can be administered by nurses in a clinical setting. PDT is a two-step process involving the application of a light-activated substance followed by exposure to light to activate this substance. The treatment results in the elimination of tumour cells while leaving the healthy skin unharmed. This article provides an introduction to PDT for nurses who may in the future be involved in setting up a PDT service within their practice area.

Age Distribution↗