Biomedical subjects

Andreu Palou

Publications and source records attributed to Andreu Palou.

At least 19 recordsLinked to original sources

PubMed2006

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. Changes in the expression of genes related to thermogenesis and fatty acid oxidation and levels of phosphorylated retinoblastoma protein were analyzed in WAT depots of adult NMRI male mice acutely injected with ATRA or vehicle, together with biometric and blood parameters. Body fat loss after ATRA treatment was unaccompanied by any increase in circulating nonesterified fatty acids or ketone bodies and accompanied by increased rectal temperature. The treatment triggered an up-regulation of the mRNA levels of uncoupling proteins 1 and 2, peroxisome proliferator-activated receptor gamma coactivator-1alpha, peroxisome proliferator-activated receptor alpha, muscle- and liver-type carnitine palmitoyltransferase 1, and subunit II of cytochrome oxidase in different WAT depots. Levels of phosphorylated retinoblastoma protein in WAT depots were increased after ATRA treatment. Adipocyte size was reduced, and the number of multilocular adipocytes was increased in inguinal WAT of ATRA-treated mice. The results indicate that ATRA favors the acquisition of brown adipose tissue-like properties in WAT. Understanding the mechanisms and effectors involved in the remodeling of WAT can contribute to new avenues of prevention and treatment of obesity and type 2 diabetes.

Adipose Tissue↗

PubMed2006

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↗

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↗

PubMed2005

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. Water dispersible beadlets containing BC are a good choice and can produce the greatest BC uptake when compared to the above vehicles, but other beadlet components could alter the results. Dimethylsulfoxide (DMSO) could be a good alternative since it has low toxicity and it enhances the penetration of substances across biologic membranes. We aimed to characterize an appropriate model for delivering all-trans-BC to lung cells in culture and knowing its metabolism. All-trans-BC 5 microM was administered to BEAS-2B cells in beadlets or DMSO, and medium and cell samples were taken at different times. The levels of BC and its main isomers and metabolites were determined by HPLC. All-trans-BC reached the same levels in the medium (about 3.5 microM) either when supplied in beadlets or in DMSO, and, with beadlets, 13-cis-BC was also detected. However the amount of all-trans-BC taken up by the cells was the triple when delivered by DMSO. With both vehicles, intracellular all-trans-BC levels reached its maximum after 24 h of treatment, remaining equal after 72 h. The 9-cis and 13-cis isomers of BC, and oxidized metabolites, were also detected in the cells although in smaller proportion than all-trans-BC, especially with DMSO. An LDH assay did not suggest toxicity of beadlets, DMSO or BC itself. In conclusion, DMSO seems the most appropriate vehicle for delivering BC to lung cells in vitro, and we present a model that allows studying the effects of BC and its metabolism in the lung human BEAS-2B cell line.

Bronchi↗

PubMed2005

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). To establish the window of benefit, it is necessary to identify early markers of effect and to obtain insight in the mechanism of action of beta-carotene, in the absence and presence of environmental risk factors. Genomics technologies are well suited to dissect the mechanisms of action and identify the markers of effect. Human cell lines can be used to analyse the effects of beta-carotene, but exposure studies with beta-carotene show that cell lines display a widely variant behaviour, which hampers translation to the in vivo situation in humans. Alternatively, animal studies can be used. Especially the ferret seems to be a good model, but little sequence information of this species is available. However, heterologous hybridization on human cDNA seems possible and provides and a new tool for molecular analysis of health effects of beta-carotene.

Animals↗

PubMed2004

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. They also demonstrate a direct inhibitory effect of RA on leptin expression in both white and brown adipocyte cell cultures, and constitute first proof of the involvement of both RA receptors (RARs) and rexinoid receptors (RXRs) in this effect. Reduction of leptin levels by specific nutrients is of potential interest from a clinical point of view.

3T3-L1 Cells↗

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 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 aim of the present work was to analyse the effects of RU486 on the expression of uncoupling proteins (UCPs) in brown adipocytes. In culture-grown, differentiated brown adipocytes, placed in a serum-free medium to exclude the presence of progesterone or glucocorticoids, RU486 stimulated UCP1 expression at both the mRNA and protein levels. These effects could be mediated by PR, GR or other unknown mechanisms but do not seem to be due to its anti-progestin or anti-glucocorticoid actions. The results suggest that the steroid RU486 has a direct action on adipocytes which could be useful for stimulating non-shivering BAT thermogenesis and therefore is of interest in obesity studies.

Adipocytes↗

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↗

PubMed2004

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. beta(3)-AR Trp64Arg and UCP1 -3826A-->G genotypes were determined by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). UCP1 -3826G allele frequency was higher in men than in women (0.31 v 0.22, P = .015) and in obese women than in non-obese women (0.31 v 0.17, P = .008). Women carriers of the Arg64 or the alleles also showed higher leptin levels than noncarriers. Multiple linear regression analysis showed that the Arg64 allele is associated with higher leptin levels after the adjustment for gender, age, WHR, and the degree of glucose tolerance. In conclusion, the beta(3)-AR Trp64Arg polymorphism might have an impact on the mechanisms involved in leptin release from adipose tissue. Furthermore, our results agree with the previously reported association between UCP1 -3826G allele and obesity and point to a gender-related effect.

Adipocytes↗

PubMed2004

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. METHODS: Three-week-old mice were fed standard chow or a vitamin A deficient diet for 10 weeks, after which animals on both diets were treated with all-trans RA (ATRA, 100 mg x Kg(-1) day(-1)) or vehicle during 4 days. Levels of UCP1, RARalpha and RXRalpha in BAT were determined by immunoblotting. RESULTS: ATRA-treatment resulted in a reduction of the specific RARalpha and especially RXRalpha content in BAT that paralleled the induction of UCP1 appearance in the tissue. RARalpha and RXRalpha levels per gram of BAT were reduced in mice chronically fed the vitamin A-deficient diet. CONCLUSION: RA modulates the expression of cognate receptors in BAT, suggesting auto regulation of the retinoid effect on the thermogenic system.

Adipocytes↗

PubMed2004

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. Peroxisome proliferator-activated receptor (PPAR)-gamma2, PPARalpha, CCAAT enhancer-binding protein-alpha, and adipocyte differentiation and determination factor 1 mRNAs in gonadal white adipose tissue (gWAT) (visceral depot) and inguinal white adipose tissue (iWAT) (subcutaneous depot) and in interscapular brown adipose tissue were measured by reverse transcription-polymerase chain reaction. RESULTS: Short-term CAF diet feeding resulted in increases in body weight, adipose tissue weights, and lipid serum levels. Increased adiposity was more related to an increase in visceral fat than an increase in subcutaneous fat. This difference was associated with a higher expression of key adipogenic transcription factors (mainly PPARgamma2 and CCAAT enhancer-binding protein-alpha) in gWAT when compared with iWAT. Higher hypertrophy of gWAT was found in females, whereas males showed a higher hypertrophy of iWAT. Differential gender and depot response to CAF diet could be explained by depot and gender differential expression of key adipogenic transcription factors, especially PPARgamma2. Hence, reduced hypertrophy of female iWAT and defective thermogenesis in interscapular brown adipose tissue in response to CAF diet were related to decreased PPARgamma2 mRNA levels, whereas increased hypertrophy in male iWAT and gWAT and in female gWAT was related to a tendency toward increased PPARgamma2 mRNA levels in response to overfeeding. DISCUSSION: Our results suggest the involvement of PPARgamma2 in gender- and depot-specific effects of CAF diet on development and function in adipose tissues.

Adipose Tissue↗

PubMed2004

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↗

PubMed2004

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. RA administration to normal mice resulted in reduced resistin mRNA levels in brown and white adipose tissues, reduced circulating resistin levels, reduced body weight, and improved glucose tolerance. Resistin expression was also downregulated after dietary vitamin A supplementation in mice. The results raise the possibility that vitamin A status may contribute to modulate systemic functions through effects on the production of adipocyte-derived protein signals.

3T3 Cells↗

PubMed2003

Direct effects of testosterone, 17 beta-estradiol, and progesterone on adrenergic regulation in cultured brown adipocytes: potential mechanism for gender-dependent thermogenesis.

Previous studies suggest that sex hormones could be responsible, at least in part, for the gender-dependent thermogenesis found in the adrenergic control of brown adipose tissue (BAT) under control conditions and in response to diet and cold. Catecholamines, as well as several hormones, including sex hormones, may alter the function or expression of different adrenoceptor subtypes in brown adipocytes in vivo, and a confirmation could be provided by in vitro experiments. Therefore, the effect of testosterone, 17 beta-estradiol, progesterone, and norepinephrine (NE) on adrenergic receptor (AR) gene expression (alpha 2A-, beta 1-, -, and beta 3-AR) and lipolytic activity was investigated in differentiated brown adipocytes in culture. We report that the expression of each AR subtype gene was distinctively regulated by NE and sex hormones in brown adipocytes. Testosterone-treated cells had lower lipolytic activity and increased expression of antilipolytic receptors alpha 2A-AR. Both 17 beta-estradiol and progesterone decreased alpha 2A-AR expression and alpha 2A/beta 3-AR protein ratio, but progesterone had higher potency than 17 beta-estradiol, increasing beta-AR levels, mainly beta 3-AR expression, and enhancing lipolysis stimulated by NE. In conclusion, our results support the idea that male and female sex hormones, as a part of the hormonal environment of BAT, have direct and opposite effects on the AR balance and lipolytic activity, and they might play a role in the gender dimorphism for the recruitment process in BAT.

Adipocytes↗

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↗