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C Picó

Publications and source records attributed to C Picó.

At least 19 recordsLinked to original sources
PubMed2001

Differential expression of genes for uncoupling proteins 1, 2 and 3 in brown and white adipose tissue depots during rat development.

The different expression patterns of genes for uncoupling proteins (UCPs) 1, 2 and 3 (ucp1, ucp2 and ucp3) were studied in interscapular brown adipose tissue (BAT) and in four white adipose tissue (WAT) depots (epididymal, inguinal, mesenteric and retroperitoneal) in male rats of different ages (18 days-12 months). UCP mRNA expression levels were determined by Northern blotting. In BAT, there were high levels of expression of UCP1 and UCP3 mRNA, but no detectable levels of UCP2 mRNA. Both ucp1 and ucp3 followed a similar expression pattern with age, with high levels in suckling rats which decreased to 50% or less in rats just under 2 months old, declining thereafter until 5 months and then recovering with age. However, an additional peak of expression was observed for ucp3 at the age of 3 months. In WAT, ucp1 expression was rare: occasional expression was found for UCP1 mRNA in the retroperitoneal depot in suckling rats and in the epididymal and inguinal depots in suckling and mature adult rats. ucp2 and ucp3 had different developmental expression patterns, but these were similar for each gene in the different depots studied. UCP3 mRNA was highly expressed in rats soon after birth, it decreased until 3 months, and increased thereafter, except for the mesenteric WAT where ucp3 expression decreased until 7 months before recovering. The fact that changes with age of both ucp1 and ucp3 expression have a similar profile in BAT, which is also similar to the ucp3 and also ucp1 profiles in some WAT depots, might reflect a common regulatory pattern for the expression of these genes, and also a common function. In contrast to ucp1 and ucp3, ucp2 had a peak of expression at about 2 months, and lower expression at 3 months, suggesting different regulation and probably a different role for this UCP.

Adipose Tissue↗
PubMed2001

Ontogenesis of leptin expression in different adipose tissue depots in the rat.

Serum leptin levels and leptin mRNA expression by adipose tissue increase with age and are mainly associated with an increase in adiposity. Regional changes in both leptin production and fat distribution contribute to circulating leptin levels and may play a role in the regulation of body weight. a capacity that changes during development. Here, we have studied leptin mRNA expression in four different white adipose tissue depots (epididymal, retroperitoneal, mesenteric, inguinal; namely, EWAT, RWAT, MWAT, IWAT) and in interscapular brown adipose tissue (IBAT). We have also studied their relationship with lipid content and adiposity changes, together with serum leptin levels in male rats at different ages (18, 55, 93, 159, 212, 294 and 355 days). Serum leptin levels increased during development, reaching stable levels at the age of 7 months, and, as expected, were highly correlated with both the adiposity index (r=0.908, P<0.01) and body weight (r=0.906, P<0.01). Leptin mRNA expression also increased with age, following characteristic ontogenic patterns in every adipose tissue depot. The patterns were similar in EWAT and RWAT: leptin expression increased very rapidly during the first 55 days for EWAT and 3 months for RWAT, with a peak in the latter at 7 months, and high expression levels were retained for the rest of the study period. In IWAT and IBAT, leptin expression increased steadily during the 12-month period studied and was significantly lower than levels in EWAT and RWAT. Leptin expression in MWAT increased progressively with age to reach levels close to those of EWAT and RWAT in 10-month-old animals. The pattern of leptin expression in both EWAT and RWAT paralleled their lipid content, and leptin mRNA expression per unit of tissue lipid content was maintained high and constant from a very young age (about 2 and 3 months, respectively). However, the expression of mRNA for leptin (expressed per unit of tissue lipid concentration) in MWAT, IWAT and IBAT increased steadily during the whole period studied, without attaining the maximal levels observed in EWAT and RWAT. MWAT, IWAT and IBAT maintained their capacity to increase leptin mRNA expression in response to an additional accumulation of lipids. Our data demonstrate that there are regional-specific differences and different rates of increase of leptin gene expression within distinct depots of WAT and BAT. These changes cannot be uniquely explained by changes in adiposity or lipid content, implying that there are regional-specific regulatory mechanisms that may depend on the attenuation with age of the beta-adrenergic inhibitory signalling pathway upon leptin expression or on other factors.

Adipose Tissue↗
PubMed2000

Obesity: molecular bases of a multifactorial problem.

Obesity could well become the most common health problem of the 21st century. There are more opportunities to consume large quantities of food: big portions of tasty, varied food, at reasonable prices, are available everywhere. Moreover, our bodies are better adapted to combat weight loss than to combat weight gain, since for thousands of years our species evolved in circumstances where nutrients were in short supply. The response of each individual to diet and other environmental factors varies considerably, depending on the characteristics of his/her body weight control mechanisms. The differentiating element in the future, especially as regards the dietary and pharmacological control of obesity, will be knowledge of an individual's possible response depending on his/her genetic background. Obesity can occur as a result of genetic or acquired changes in three main types of biochemical processes, which are the main focus of this review: a)feeding control, which determines the sensations of satiety and hunger through processes that depend on an interplay between internal signals (notably leptin) and environmental factors; b) energy efficiency, in particular the activation of thermogenesis mediated by uncoupling proteins (UCPs) that makes it possible to dissipate part of the energy contained in food as heat instead of accumulating it as fat, and c) adipogenesis, the process by which cells specialised in fat storage (adipocytes) are formed, which is controlled by an interplay of transcription factors, including members of the C/EBP, PPARgamma and ADD families. The knowledge of a growing number of genes and molecules implicated in these three types of processes and of their metabolic relationships is leading toward a molecular understanding of the body weight regulatory system, and is paving the way for new methods of obesity control, especially pharmacological but also nutritional and possibly involving genetic intervention.

Adipose Tissue↗
PubMed2000

In vivo effects of CGP-12177 on the expression of leptin and uncoupling protein genes in mouse brown and white adipose tissues.

OBJECTIVE: To assess the effect of chronic treatment with CGP-12177 a beta3-adrenergic receptor (AR) agonist with beta2/beta1-AR antagonist action, on the expression of the leptin gene and of genes coding for uncoupling proteins (ucp1, ucp2 and ucp3) in brown and white adipose tissues. DESIGN: NMRI mice received a daily subcutaneous injection of CGP-12177 at a dose of 0.05, 0.2, 0.5 or 1 mg/kg for 15 days. The specific levels of the mRNAs of interest were analysed in interscapular brown adipose tissue (BAT) and in two white adipose tissue (WAT) depots, inguinal (IWAT) and epididymal (EWAT). RESULTS: No changes in food intake or body weight were detected at any dose of CGP-12177. In the two WAT depots, the treatment led to enhanced expression of ucp1 and ucp3, but not of ucp2. In BAT, low doses (0.05 and 0.2 mg/kg) led to a decreased expression of the three ucp genes, whereas a slight stimulatory effect on the three ucp genes was elicited with a high dose (1 mg/kg). Treated animals displayed increased expression of leptin in BAT and, to a lesser extent, in IWAT, but not in EWAT. CONCLUSION: The results reveal that simultaneous stimulation of the expression of certain ucp genes and the leptin gene can be achieved, and suggest that adrenergic regulation of the leptin gene and of genes of the ucp family in adipose tissues is the result of complex interactions between the different beta-AR pathways.

Adipose Tissue↗
PubMed2000

Secretory granules of endocrine and chief cells of human stomach mucosa contain leptin.

BACKGROUND: Leptin plays an important role in the control of food intake and body weight homeostasis. In humans, leptin is produced by adipocytes, placental cells and secretory cells of the mammary epithelium. Recently, it has been reported that stomach glands produce leptin in rats. OBJECTIVE: To test the expression of leptin protein in human stomach and localize, by immunocytochemistry, the specific cell type producing leptin. DESIGN: Endoscopic stomach biopsies of six patients were used to investigate leptin production in the fundic epithelium using reverse transcription polymerase chain reaction (RT-PCR) of RNA. Leptin protein was detected by immunoblot analysis and localized by immunohistochemistry and ultrastructural immunocytochemistry (immunogold method). RESULTS: Human gastric epithelium expresses leptin mRNA and leptin protein. The cells in the lower half of the stomach glands were immunoreactive for leptin. Ultrastructural immunocytochemistry showed leptin immunoreactivity in the pepsinogen granules of chief cells, but the granules of a specific endocrine cell type in the basal portion of the glands were also positive. CONCLUSIONS: Our results suggest that gastric leptin could function in the short-term system to control feeding behaviour and is probably secreted in the stomach lumen by chief cells and into the stomach circulation by a special type of endocrine cell.

Adult↗
PubMed2000

Opposite effects of feeding a vitamin A-deficient diet and retinoic acid treatment on brown adipose tissue uncoupling protein 1 (UCP1), UCP2 and leptin expression.

The relationship between interscapular brown adipose tissue (IBAT) thermogenic potential and vitamin A status was investigated by studying the effects of feeding a vitamin A-deficient diet and all-trans retinoic acid (tRA) treatment on body weight and IBAT parameters in mice. Feeding a vitamin A-deficient diet tended to trigger opposite effects to those of tRA treatment, namely increased body weight, IBAT weight, adiposity and leptin mRNA expression, and reduced IBAT thermogenic potential in terms of uncoupling protein 1 (UCP1) mRNA and UCP2 mRNA expression. The results emphasize the importance of retinoids as physiological regulators of brown adipose tissue.

Adipose Tissue, Brown↗
PubMed1999

Brown adipose tissue response to cafeteria diet-feeding involves induction of the UCP2 gene and is impaired in female rats as compared to males.

Noradrenaline-dependent brown adipose tissue (BAT) thermogenesis is activated by the cold and excess energy intake, largely depends on the activity of the uncoupling protein 1 (UCP1), and is mediated mainly through the beta3-adrenoceptor (beta3-AR). We investigated the expression of ucp2, a gene that encodes a putative UCP1-like uncoupling protein, along with that of ucp1 and beta3-ar, in the interscapular BAT (IBAT) of male and female rats chronically fed a cafeteria diet. After 3 months on this diet, male rats attained a 34% excess body mass and showed IBAT hypertrophy and increased IBAT thermogenic potential, in terms of both UCP1 and UCP2 mRNA expression (both by 1.6-fold), UCP1 protein expression (by 1.75-fold) and GDP binding to IBAT mitochondria (by 2.2-fold); female rats attained a larger excess body weight (50%) and their IBAT, although hypertrophied, showed no signs of increased thermogenic potential per gram of tissue. Interestingly, the IBAT of female rats was already activated compared to males. Treatment of mouse brown adipocytes in primary culture with noradrenaline also triggered a dose-dependent increase of the levels of UCP1 mRNA and UCP2 mRNA. Retroregulatory down-regulation of the beta3-AR mRNA levels was found in the two models used. The results support a physiological role for UCP2, along with UCP1, in rodent BAT thermogenesis.

Adipose Tissue, Brown↗
PubMed1998

Stimulation of uncoupling protein synthesis in white adipose tissue of mice treated with the beta 3-adrenergic agonist CGP-12177.

The effects of chronic treatment with the beta 3-adrenergic receptor agonist CGP-12177 on uncoupling protein (UCP) synthesis in interscapular brown adipose tissue (IBAT), various white fat depots and skeletal muscle have been examined in the mouse (daily injection for 15 days at a dose of 0.5 mg/kg). The treatment increased the IBAT UCP content and led to the expression of UCP in inguinal white adipose tissue. The increase in IBAT UCP content took place in the absence of tissue hypertrophy, and despite the increase in total body UCP content, no changes in body weight were observed after the treatment. The results confirm that ectopic expression of UCP in non-BAT tissues can be induced after chronic adrenergic stimulation.

Adipose Tissue↗
PubMed1998

Sex-associated differences in cold-induced UCP1 synthesis in rodent brown adipose tissue.

The effects of acute and chronic acclimation to cold on uncoupling protein 1 (UCP1) levels, as well as on GDP-binding to mitochondria, cytochrome c oxidase activity and mitochondrial protein concentration in brown adipose tissue (BAT) of intact male and female rats have been analyzed. Results reveal that females rats are more sensitive to cold because their threshold temperature for the thermogenic response is set at a higher value (around 22 degreesC) than that of males (around 18 degreesC), hence leading to differences in BAT UCP1 levels between the sexes at different environmental temperatures. In vitro experiments showed that steroid hormones, beta-estradiol, estrone and progesterone, can reduce norepinephrine-induced UCP1 synthesis in brown adipocytes differentiated in primary culture. Thus the different sex-associated response of cold-induced thermogenesis in rats does not appear to be explained by a direct action of sex steroids upon the adipocyte, implying that other factors in the thermogenic regulatory system must be involved.

Adipose Tissue, Brown↗
PubMed1998

The uncoupling protein, thermogenin.

The uncoupling protein (UCP) or thermogenin is a 33 kDa inner-membrane mitochondrial protein exclusive to brown adipocytes in mammals that functions as a proton transporter, allowing the dissipation as heat of the proton gradient generated by the respiratory chain and thereby uncoupling oxidative phosphorylation. Thermogenesis (heat production) in brown adipose tissue, which is activated in response to cold exposure or chronic overeating, depends largely on UCP activity. Norepinephrine, released from sympathetic terminals and acting via beta-adrenoceptors and cAMP, is the main positive regulator of both UCP synthesis and activity. Brown fat thermogenesis plays a critical role in thermoregulation and in overall energy balance, at least in rodents. Manipulation of thermogenesis, whether through UCP or through analogous uncoupling proteins, could be an effective strategy against obesity.

Adipose Tissue, Brown↗
PubMed1998

2-Methoxyestradiol, an endogenous metabolite of 17beta-estradiol, inhibits adipocyte proliferation.

The effects of 2-methoxyestradiol (2ME), a naturally occurring mammalian metabolite of 17beta-estradiol, on adipocyte growth has been investigated in mouse brown adipose tissue precursor cells developed in primary culture. 2ME inhibits brown adipocyte proliferation in a dose-response manner (IC50 = 1.7 x 10(-6) M for DNA synthesis), with much higher potency than its hormone precursor 17beta-estradiol, and cells acquire the typical differentiated morphology--more round with a higher content of triglycerides. 2ME causes similar effects in the immortal brown adipocyte tumor-derived hibernoma cell line HIB 1B and the immortal 3T3-F442A white adipocyte line. These findings suggest a possible role for 2ME in adipocyte proliferation, and probably in the differentiation process, entering the cells in the adipogenic program.

2-Methoxyestradiol↗
PubMed1997

Rats receiving the slimming agent oleoyl-estrone in liposomes (Merlin-2) decrease food intake but maintain thermogenesis.

Oleoyl-estrone given i.v.--incorporated in liposomes to mimic lipoprotein delivery--(Merlin-2) to normal weight rats, induces a dose-dependent weight loss. Analysis of body composition showed that body protein concentration was preserved and fat stores wasted. The respiratory quotient was consistent with the massive oxidation of body fat, since the diet contained practically no lipid. Appetite was affected by Merlin-2, and thus food intake showed a transient decrease. But oxygen consumption (and basal metabolic rates) was kept practically unchanged at the levels of the controls, i.e. higher than needed to oxidize the food ingested during the weight loss period. Brown adipose tissue uncoupling protein levels were proportionally preserved with a 2-week treatment, but it lost a substantial amount of lipid. In conclusion, Merlin-2 is a slimming agent with considerable potential given its powerful fat-wasting action, since it maintains thermogenesis despite lowered energy intake.

Adipose Tissue↗
PubMed1996

In vitro and in vivo induction of brown adipocyte uncoupling protein (thermogenin) by retinoic acid.

The effects of retinoic acid (RA) isomers (all-trans-RA and 9-cis-RA) on the appearance of uncoupling protein (UCP; thermogenin), the only unequivocal molecular marker of the brown adipocyte differentiated phenotype, have been investigated in primary cultures of brown adipocytes, in the brown adipocyte cell line HIB 1B and directly in intact mice. The results obtained with cultured cells indicate that retinoids function as inducers of the appearance of UCP and, at the same time, partially inhibit brown adipocyte cell proliferation. The two RA isomers displayed similar effectiveness as UCP inducers, their effect being comparable with that triggered by noradrenaline, so far considered to be the main modulator of UCP gene expression. The effectiveness of retinoids as UCP inducers was dependent on the stage of brown adipocyte differentiation, being maximal in confluent primary cells and in the medium-late differentiation stage of HIB 1B cells. Corroborating the results obtained in vitro, we show that administration of all-trans-RA or 9-cis-RA to mice leads to an increase in their brown adipose tissue specific UCP content. 9-cis-RA treatment also prevented the loss of UCP on cold deacclimation. To our knowledge, this is the first report of a stimulatory effect of retinoid compounds on UCP induction in vivo.

Adipocytes↗
PubMed1996

Effect of selective beta-adrenoceptor stimulation on UCP synthesis in primary cultures of brown adipocytes.

Given the co-existence of the three beta-adrenoceptor (beta AR) subtypes (beta 1AR, beta 2AR and beta 3AR) in brown adipocytes, the present study was undertaken to determine the relative importance of these in the induction of UCP synthesis in mouse BAT precursor cells in primary culture. Cells at different stages of differentiation were exposed to different beta AR agonists: prenalterol (a selective beta 1AR agonist), salbutamol or clenbuterol (selective beta 2AR agonists), or BRL 37344 (a selective beta 3AR agonist). As with the endogenous agonist, noradrenaline, and the non-selective beta AR agonist, isoprenaline, all four beta AR agonists induced UCP in the confluent stage of the cells, but with different potencies, and with the highest induction being seen after clenbuterol or BRL 37344 treatment. Cells in the confluent stage of development were the most sensitive to the effects of the agonists, although clenbuterol and BRL 37344 induced a weak UCP synthesis in pre-confluent cells. None of these beta AR agonists were able to induce UCP synthesis in the post-confluent period. The responses to prenalterol and salbutamol were inhibited by propranolol at relatively low concentrations, suggesting their effects were mediated by beta 1AR and beta 2AR, respectively. However, propranolol was a particularly weak antagonist of BRL 37344 and, unexpectedly, of the clenbuterol UCP responses, which suggests that both induce UCP synthesis via the beta 3AR. In summary, the beta 3AR is the most important adrenoceptor coupled to the induction of UCP synthesis, although both beta 1AR and beta 2AR activation may make a contribution. However, all three beta AR subtypes do not become fully functional until cultured cells become confluent.

Adipose Tissue, Brown↗
PubMed1995

Decrease of the pool of amino acids adsorbed on blood cell membranes caused by starvation in rats.

The effect of 24 h starvation on the pool of amino acids adsorbed on the blood cell membranes was determined in Wistar rats. Aortic and iliac blood was analysed. 24 h starvation induced a significant decrease in the combined essential amino acids adsorbed on the blood cell membranes, in both arterial and venous blood, without affecting whole-blood levels (adsorbed + non-adsorbed). The same tendency was extended to most of the individual amino acids. This finding indicates that this pool of adsorbed amino acids has a rapid turnover and probably plays a physiological role in a situation of exogenous food deprivation.

Adsorption↗
PubMed1995

Protein and amino acid intake in cafeteria fed obese rats.

Food selection pattern and portal blood amino acid profile were examined in rats given a cafeteria diet. Compared to standard-diet fed rats, cafeteria-diet fed rats consumed more energy. Increase in energy intake was attributable to an increase in fat intake. Protein intake was slightly higher and carbohydrate intake remained constant and was similar to levels consumed by standard-diet fed rats. The cafeteria rats took up higher quantities of Phenylalanine+Tyrosine, Arginine, Histidine, Lysine, Leucine, Isoleucine, Valine, Threonine, and Glycine, lower quantities of Tryptophan and the same quantity of Methionine+Cysteine vs. control rats. Portal concentrations of Serine, Threonine, Tryptophan and Lysine were significantly higher in cafeteria-diet fed rats than in standard-diet fed rats. This can be interpreted in such a way that, on the whole, the quality of protein ingested by cafeteria and control rats is similar. No statistical differences in the ingestion of individual amino acids were observed between different days of the period of cafeteria diet feeding, thus the idea of a strict control of protein ingestion irrespective of the obese status is reinforced.

Amino Acids↗
PubMed1994

Stabilization of the mRNA for the uncoupling protein thermogenin by transcriptional/translational blockade and by noradrenaline in brown adipocytes differentiated in culture: a degradation factor induced by cessation of stimulation?

The stability of the mRNA coding for the uncoupling protein thermogenin was investigated in mouse brown-fat cells differentiated in culture. After 7 days in culture, the cells were stimulated for 24 h with noradrenaline, and a high level of thermogenin mRNA was then observed. If noradrenaline treatment was continued, the mRNA level remained high, but, upon withdrawal of noradrenaline, the level decreased rapidly, with a half-life of only 2.7 h. The presence of transcriptional (actinomycin) or translational (cycloheximide) inhibitors prolonged the apparent half-life by about 50%. The presence of noradrenaline during transcriptional blockade led to a further stabilization of thermogenin mRNA. It was concluded that an induced (or short-lived) gene product is important for thermogenin mRNA degradation. Direct interaction of noradrenaline with the cultured brown adipocytes could apparently not mimic the paradoxical destabilization of thermogenin mRNA in vivo, previously observed in the cold-exposed mouse [Jacobsson, Cannon and Nedergaard (1987) FEBS Lett. 244, 353-356], indicating significant differences between the systems in vitro and in vivo.

Adipocytes↗