RARgamma and TRbeta expressions are decreased in PBMC and SWAT of obese subjects in weight gain.

In order to evaluate the expression of nuclear receptors at the peripheral level in obese subjects, messenger RNA (mRNA) levels of different isoforms of retinoic acid receptor (RAR), triiodothyronine (TR), and peroxisome proliferator-activated receptor (PPAR) were determined and compared in peripheral mononuclear blood cells (PBMC) and subcutaneous white adipose tissue (SWAT). Twelve lean subjects and 68 obese subjects divided into weight gain (WG), weight-stable (WS), and weight loss (WL) groups were studied. Nuclear receptor mRNA levels were assessed in PBMC and SWAT using a quantitative real-time reverse transcription polymerase chain reaction method. mRNA levels of RARgamma were significantly lower in PBMC of obese subjects (WG -19%, WS -30%, and WL -24.7%) as in SWAT of WG (-50%). Lower mRNA levels of TRbeta were observed in PBMC and SWAT of WG (-50.7% and -28%, respectively) just as for TRalpha in PBMC of WG (-19%). In contrast, retinoid X receptors alpha (RXRalpha) and RARalpha mRNA levels were higher in PBMC of obese subjects (+53% and +54.5% in WG, +56% and +67% in WS, and +68% and +49.7% in WL, respectively), while expression of RXRalpha was lower in SWAT of WG (-24.5%). As for PPARgamma, its mRNA level was significantly higher in PBMC of WG subjects (+34%) while its expression was not modified in SWAT, contrary to the PPARgamma2 isoform which was significantly higher. These data show that in both adipose tissue and blood compartment of obese subjects, expressions of RARgamma and TRbeta were downregulated. Thus, we suggest that the expression in PBMC of obese subjects may constitute new cellular indicators of nuclear receptor retinoid and thyroid status.

RARã and TRBeta expressions are decreased in PBMC and SWAT of obese subjects in weight gain

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In order to evaluate the expression of nuclear receptors at the peripheral level in obese subjects,messenger RNA (mRNA) levels of different isoforms of retinoic acid receptor (RAR), triiodothyronine(TR), and peroxisome proliferator-activated receptor (PPAR) were determined and compared in peripheral mononuclear blood cells (PBMC) and subcutaneous white adipose tissue (SWAT). Twelve lean subjects and 68 obese subjects divided into weight gain (WG), weight-stable (WS), and weight loss (WL) groups were studied. Nuclear receptor mRNA levels were assessed in PBMC and SWAT using a quantitative real-time reverse transcription polymerase chain (..) (AU)

Role of adipogenic and thermogenic genesin susceptibility or resistance to developdiet-induced obesity in rats

The aim of the present work was to assess whether changes in adipose tissue geneexpression related with adipogenesis and/or thermogenesis could be involved in themechanism conferring susceptibility or resistance to develop obesity in high-fat fedoutbreed rats. For this purpose, male Wistar rats were fed with standard laboratorydiet (control group) or high fat diet. After 15 days, two groups of rats with significantdifferences on body weight gain in response to the high fat diet were characterizedand identified as diet-induced obesity (DIO) and diet resistant (DR) rats. A significantincrease in visceral white adipose tissue (WAT) PPARã and aP2 (p<0.05)mRNA levels associated to a decrease in RARã expression (p<0.05) was observed inDIO rats, suggesting an increase of adipogenesis. Furthermore, our data showed amarked increase in brown adipose tissue (BAT) of UCP1 mRNA in DIO animals(p<0.01) (without affecting PGC-1á gene expression), whereas no changes werefound in WAT UCP2 gene expression. All these data suggest that the variationsfound in the expression pattern of PPARã, aP2 and RARã by high-fat diet could beinvolved, at least in part, in the differences in body weight gain and adiposityobserved between DR and DIO animals. The compensatory adaptations through theincrease in energy expenditure by changes on the expression levels of UCP1 seem notto be enough to avoid the obesity onset in the DIO group (AU)

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Role of adipogenic and thermogenic genes in susceptibility or resistance to develop diet-induced obesity in rats

The aim of the present work was to assess whether changes in adipose tissue geneexpression related with adipogenesis and/or thermogenesis could be involved in themechanism conferring susceptibility or resistance to develop obesity in high-fat fedoutbreed rats. For this purpose, male Wistar rats were fed with standard laboratorydiet (control group) or high fat diet. After 15 days, two groups of rats with significantdifferences on body weight gain in response to the high fat diet were characterizedand identified as diet-induced obesity (DIO) and diet resistant (DR) rats. A significantincrease in visceral white adipose tissue (WAT) PPARã and aP2 (p<0.05)mRNA levels associated to a decrease in RARã expression (p<0.05) was observed inDIO rats, suggesting an increase of adipogenesis. Furthermore, our data showed amarked increase in brown adipose tissue (BAT) of UCP1 mRNA in DIO animals(p<0.01) (without affecting PGC-1á gene expression), whereas no changes werefound in WAT UCP2 gene expression. All these data suggest that the variationsfound in the expression pattern of PPARã, aP2 and RARã by high-fat diet could beinvolved, at least in part, in the differences in body weight gain and adiposityobserved between DR and DIO animals. The compensatory adaptations through theincrease in energy expenditure by changes on the expression levels of UCP1 seem notto be enough to avoid the obesity onset in the DIO group (AU)

No disponible

Role of adipogenic and thermogenic genes in susceptibility or resistance to develop diet-induced obesity in rats.

The aim of the present work was to assess whether changes in adipose tissue gene expression related with adipogenesis and/or thermogenesis could be involved in the mechanism conferring susceptibility or resistance to develop obesity in high-fat fed outbreed rats. For this purpose, male Wistar rats were fed with standard laboratory diet (control group) or high fat diet. After 15 days, two groups of rats with significant differences on body weight gain in response to the high fat diet were characterized and identified as diet-induced obesity (DIO) and diet resistant (DR) rats. A significant increase in visceral white adipose tissue (WAT) PPARgamma and aP2 (p < 0.05) mRNA levels associated to a decrease in RARgamma expression (p < 0.05) was observed in DIO rats, suggesting an increase of adipogenesis. Furthermore, our data showed a marked increase in brown adipose tissue (BAT) of UCP1 mRNA in DIO animals (p < 0.01) (without affecting PGC-1alpha gene expression), whereas no changes were found in WAT UCP2 gene expression. All these data suggest that the variations found in the expression pattern of PPARgamma, aP2 and RARgamma by high-fat diet could be involved, at least in part, in the differences in body weight gain and adiposity observed between DR and DIO animals. The compensatory adaptations through the increase in energy expenditure by changes on the expression levels of UCP1 seem not to be enough to avoid the obesity onset in the DIO group.

Effect of vitamin A content in cafeteria diet on the expression of nuclear receptors in rat subcutaneous adipose tissue.

The aim of this study was to determine the effects of cafeteria diet containing control or elevated level of vitamin A on the expression of nuclear receptors in adipose tissue. Male Wistar rats were submitted to 3 experimental diets during 8 weeks, a standard diet and two hyper-energetic, hyperlipidic "cafeteria" diets containing normal (Caf) or higher (Caf+) vitamin A level. During the experiment, body weights and energy intakes were measured. At the end of the experimental period, subcutaneous adipose tissue (Swat) and all the fat mass were removed and weighted. Nuclear receptors mRNA levels of RARalpha, RARgamma, RXRalpha, PPARgamma were measured in the Swat by a real-time semi-quantitative RT-PCR method. We observed that energy intake of Caf+ and Caf groups was significantly higher than that of the control group. Despite a higher increase of the energy intake in the Caf group compared to the Caf+ group, no significant difference was observed in the body weight gain of the Caf+ compared to the Caf group. The Caf+ and Caf diets led to a significant increase of adipose tissue in cafeteria groups as observed in the Swat depot. The mRNA levels of PPARgamma and RXRalpha were significantly increased in the Caf+ group as compared to control group, with a significant positive correlation between these two parameters. Expressions of RARalpha and RARgamma were not modified in experimental groups compared to controls. In conclusion, 8-week exposure to cafeteria diets with normal and higher levels of vitamin A led to an increase of adiposity in rats, associated, only in the group fed with the higher vitamin A level cafeteria diet, with an increase of PPARgamma and RXRalpha expressions in subcutaneous adipose tissue.

Effect of vitamin A content in cafeteria diet on the expression of nuclear receptors in rat subcutaneous adipose tissue

The aim of this study was to determine the effects of cafeteria diet containing control or elevated level of vitamin A on the expression of nuclear receptors in adipose tissue. Male Wistar rats were submitted to 3 experimental diets during 8 weeks, a standard diet and two hyper-energetic, hyperlipidic "cafeteria" diets containing normal (Caf) or higher (Caf+) vitamin A level. During the experiment, body weights and energy intakes were measured. At the end of the experimental period, subcutaneous adipose tissue (Swat) and all the fat mass were removed and weighted. Nuclear receptors mRNA levels of RARa, RARg, RXRa, PPARg were measured in the Swat by a real-time semi-quantitative RT-PCR method. We observed that energy intake of Caf+ and Caf groups was significantly higher than that of the control group. Despite a higher increase of the energy intake in the Caf group compared to the Caf+ group, no significant difference was observed in the body weight gain of the Caf+ compared to the Caf group. The Caf+ and Caf diets led to a significant increase of adipose tissue in cafeteria groups as observed in the Swat depot. The mRNA levels of PPARg and RXRa were significantly increased in the Caf+ group as compared to control group, with a significant positive correlation between these two parameters. Expressions of RARa and RARg were not modified in experimental groups compared to controls. In conclusion, 8-week exposure to cafeteria diets with normal and higher levels of vitamin A led to an increase of adiposity in rats, associated, only in the group fed with the higher vitamin A level cafeteria diet, with an increase of PPARg and RXRa expressions in subcutaneous adipose tissue

El objetivo del presente trabajo consiste en determinar las consecuencias de un alto contenido en vitamina A en dieta de cafetería sobre la expresión de receptores nucleares en el tejido adiposo. Así, ratas macho Wistar se dividieron en tres grupos : Durante 8 semanas, el grupo control se alimentó con pienso estándar, mientras que los grupos tratados recibieron una dieta rica en grasa (dieta de cafetería) enriquecida (Caf+) o no (Caf) con vitamina A. El peso corporal y la ingesta se determinaron durante todo el experimento. Al final del tratamiento, se pesó el tejido adiposo subcutáneo (Swat) y las otras reservas de grasa. Los niveles de ARNm de los receptores nucleares RARa, RARg, RXRa, PPARg se determinaron en el Swat con un método semi-cuantitativo de RT-PCR en tiempo real. Las ingestas energéticas de los grupos Caf+ y Caf fueron significativamente mayores que las del grupo control. A pesar del aumento en la ingesta del grupo Caf respecto del Caf+, no se observaron diferencias significativas en el aumento de peso corporal entre ambos grupos. Además, las dietas de los grupos Caf+ y Caf provocaron un claro aumento del tamaño de las reservas de grasa, incluido el peso del Swat. Los niveles de ARNm de PPARg yRXRa se incrementaron significativamente en el grupo Caf+ respecto del control, con correlación positiva entre ambos. En cambio, no se modificó la expresión de RARa y RARg. En suma, 8 semanas de alimentación con dieta de cafetería con niveles normales o elevados de vitamina A dan lugar a aumento de la adiposidad en la rata, asociado con aumento de la expresión de PPARg y RXRa en el tejido adiposo subcutáneo solo en el grupo que recibió suplemento de vitamina A

Relationship between peroxisome proliferator-activated receptor gamma and retinoic acid receptor alpha gene expression in obese human adipose tissue.

OBJECTIVE: To investigate in human adipose tissue a possible relationship between per oxisome proliferator-activated receptor gamma (PPARgamma) and retinoic acid receptor alpha (RARalpha) gene expression, two genes involved in the control of adipocyte differentiation. SUBJECTS: Ten lean control women (age 31-60 y, body mass index (BMI) 18-24.7 kg/m(2)) and an obese group of 15 women (age 27-62 y, BMI 30-57.5 kg/m(2)), of whom 10 subjects were in weight-gain phase and five were in weight-loss phase. MEASUREMENTS: We assessed the relative PPARgamma and RARalpha mRNA levels in subcutaneous abdominal adipose tissue using a real-time PCR method. RESULTS: PPARgamma mRNA level were significantly increased (+91%; P<0.01) in obese women compared to lean control women. In the obese group, we observed a PPARgamma mRNA level 42% lower in weight-loss obese than in weight-gain obese subjects. We obtained a positive correlation (r=0.56; P<0.01) between PPARgamma mRNA level and the BMI of all subjects. Relative mRNA abundance level of RARalpha in subcutaneous adipose tissue of obese subjects is significantly lower than in control subjects (-56%, P<0.01), and a negative correlation was found between PPARgamma and RARalpha mRNA levels in subcutaneous adipose tissue of subjects study (r=-0.75; P<0.01). CONCLUSION: Our findings suggest that obesity is associated with an inverse relationship between PPARgamma and RARalpha expressions in human subcutaneous adipose tissue. Modulations of nuclear receptor profile could be an important event in the body's early adaptive mechanisms promoting adipose tissue plasticity and leading to the onset of obesity.

Effect of a pharmacological activation of PPAR on the expression of RAR and TR in rat liver.

It has recently been shown that high-fat diets induce the expression of peroxisome proliferator-activated receptor (PPAR) with a concomitant decrease in expression of retinoic acid (RAR) and triiodothyronine (TR) receptors in rat liver. The authors have suggested that PPAR activation may be responsible for these modifications in nuclear receptor expression. With the aim of gaining further insight into a possible relationship between the patterns of expression of these receptors, we have examined, using a pharmacological model, the effect of a strong and specific PPAR activation induced by bezafibrate, a peroxisome proliferator agent. Activation of PPAR was evaluated by quantifying PPARalpha mRNA and acyl-CoA oxidase mRNA. The expression of RAR and TR was determined by assaying the binding properties of these nuclear receptors and by quantifying the mRNA level of RARbeta and TRalpha1,beta1 isoforms. After a 10 day treatment of young rats, induction of PPAR (PPARalpha mRNA was increased by 40% [P < 0.05 and acyl-CoA oxidase mRNA by 411% [P<0.001]) and a concomitant decrease of RAR and TR expression (Maximal Binding Capacity was decreased by 21 and 26%, respectively [P<0.05]) in the liver was observed. RXRalpha mRNA expression was unchanged by treatment. Cross-talk between RAR, TR and PPAR signalling pathways may be implicated in the new patterns of nuclear receptor expression observed. The decreased expression of RAR and TR reported here could provide a novel element for the understanding of the link between PPAR and tumorigenesis in rat liver.

Exposure to an obesity-inducing diet early affects the pattern of expression of peroxisome proliferator, retinoic acid, and triiodothyronine nuclear receptors in the rat.

Since evidence has appeared that alpha and gamma isoforms of the peroxisome proliferator receptors (PPARs) are involved in the regulation of triglyceride homeostasis and in the control of the differentiation of adipocytes that is required for the development of obesity, a large number of studies have investigated the physiologic role of nuclear receptors in the control of energy balance. The aim of this study was to determine the early effects of an obesity-inducing diet on the expression of PPAR alpha and gamma and other nuclear receptors such as all-trans retinoic acid receptor (RAR) and triiodothyronine receptor (TR), which all form functional heterodimers with a common partner, the 9-cis retinoic acid receptor (RXR). The experiment used a cafeteria diet where 60% of the energy was supplied as lipids. This diet was offered to young rats for 8 and 28 days and the expression of nuclear receptors was determined at the end of each experimental time period (1) in the liver by assaying the binding properties of RAR and TR and by quantifying mRNA levels of RAR beta, TR alpha(1)beta(1), RXR alpha, and PPAR alpha, and (2) in the white adipose tissue (WAT) by quantifying mRNA levels of RAR alpha, RXR alpha, TR alpha(1)beta(1), and PPAR gamma(2). After 8 days of cafeteria diet a significant decrease of RAR and TR maximal binding capacity (MBC) was observed in the liver (-20.1% and -35.0%, respectively, P <.05) and the level of the mRNA of RAR beta was significantly decreased (-17.4%, P <.05). After 28 days of cafeteria diet, the level of the mRNA of PPAR alpha and acyl-CoA oxidase (ACOX) was significantly increased (+54.5% and +37.8%, P <.01 and P <.05, respectively), whereas the MBC of RAR and TR was significantly decreased (-16.0% and -23.4%, P <.01), as were the mRNA levels of RAR beta and TR alpha(1) beta(1) (-28.5% and -32.0%, P <.05). The level of RXR alpha mRNA was unchanged. In WAT, the mRNA level of PPAR gamma(2) was significantly increased after 28 days of cafeteria diet (+49.5%, P <.05) and the mRNA levels of RAR alpha and TR alpha(1) beta(1) significantly decreased (-22.3% and -31.0%, P <.05). These results as a whole showed that a high-fat diet can induce early modifications in the pattern of expression of nuclear receptors in the liver and the WAT. These modifications could be compatible with an early adaptive phenomenon. Further investigations are necessary to better understanding the link between the modifications of the pattern of expression of these receptors and plasticity of adipose tissue leading to the onset of obesity.

Effect of a pharmacological activation of PPAR on the expression of RAR and TR in rat liver.

It has recently been shown that high-fat diets induce the expression of peroxisome proliferator-activated receptor (PPAR) with a concomitant decrease in expression of retinoic acid (RAR) and triiodothyronine (TR) receptors in rat liver. The authors have suggested that PPAR activation may be responsible for these modifications in nuclear receptor expression. With the aim of gaining further insight into a possible relationship between the patterns of expression of these receptors, we have examined, using a pharmacological model, the effect of a strong and specific PPAR activation induced by bezafibrate, a peroxisome proliferator agent. Activation of PPAR was evaluated by quantifying PPAR alpha mRNA and acyl-CoA oxidase mRNA. The expression of RAR and TR was determined by assaying the binding properties of these nuclear receptors and by quantifying the mRNA level of RAR beta and TR alpha1,beta1 isoforms. After a 10 day treatment of young rats, induction of PPAR (PPAR alpha mRNA was increased by 40% [P< 0.05 and acyl-CoA oxidase mRNA by 411% [P<0.001]) and a concomitant decrease of RAR and TR expression (Maximal Binding Capacity was decreased by 21 and 26%, respectively [P<0.05]) in the liver was observed. RXR alpha mRNA expression was unchanged by treatment. Cross-talk between RAR, TR and PPAR signalling pathways may be implicated in the new patterns of nuclear receptor expression observed. The decreased expression of RAR and TR reported here could provide a novel element for the understanding of the link between PPAR and tumorigenesis in rat liver.

Effects of the whole seed and a protein isolate of faba bean (Vicia faba) on the cholesterol metabolism of hypercholesterolaemic rats.

The aim of the present work was to analyse the hypocholesterolaemic efficiency of a Vicia faba-protein isolate in relation to the intact legume. In addition, the mechanisms underlying the effects of this isolate were investigated. Hypercholesterolaemic rats were divided into three groups and fed high-fat diets rich in cholesterol-containing casein, whole seeds of Vicia faba or the protein isolate of faba beans as protein source, for 2 weeks ad libitum. The protein isolate was prepared by isoelectric precipitation and spray dried. Analyses of serum, liver and faeces, as well as of the activity of hepatic 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase, were assessed by enzymatic methods. The rats fed on Vicia faba diets showed significantly lower body weights and energy intakes than rats fed on casein diets. The whole-seed diet induced a significant reduction in plasma triacylglycerol. Feeding rats on diets containing faba bean seeds, or the protein isolate, induced a significant decrease in plasma (LDL+VLDL)-cholesterol but not in HDL-cholesterol. Hepatic cholesterol and triacylglycerol were also reduced. The hypocholesterolaemic effects of Vicia faba were not the result of a reduction in cholesterol synthesis as assessed from HMG-CoA reductase activity, but the result of an increase in steroid faecal excretion. The faba bean-protein isolate obtained under our experimental conditions was useful in improving the metabolic alterations induced by feeding with a hypercholesterolaemic diet compared with casein. The effectiveness of the whole seeds was higher than that of the protein isolate.

High-fat diets affect the expression of nuclear retinoic acid receptor in rat liver.

The purpose of this study was to differentiate between the effects of the amount and the type of dietary lipids on the expression of the retinoic acid receptor (RAR), but also the peroxisome proliferator-activated receptor (PPAR) and the receptor of the 9-cis retinoic acid (retinoid X receptor (RXR)) in rat liver. Six groups of eight rats (5-weeks old) were fed during 4 weeks on the following diets: control 50 g vegetable oil/kg, high-fat diet 250 g vegetable oil/kg. These oils were either coconut oil (rich in saturated fatty acids) or olive oil (rich in monounsaturated fatty acids) or safflower oil (rich in polyunsaturated fatty acids, mainly as n-6). The three high-fat diets induced a significant decrease of the maximal binding capacity of RAR and of the abundance of RAR beta mRNA. Simultaneously, an increased expression of PPAR alpha mRNA was observed while no significant difference on abundance of RXR alpha mRNA was observed. The mechanisms involved are probably multiple, but one hypothesis is that a modification of the equilibrium between the nuclear receptors, resulting from an increased expression of PPAR, induces a decreased expression of RAR in rat liver.

Lipid and glucose utilization in hypercholesterolemic rats fed a diet containing heated chickpea (Cicer aretinum L.): a potential functional food.

This feeding trial evaluated the influence of a diet containing heated chickpea in a dietary induced rat model of hypercholesterolemia in order to assess some possible protective and therapeutic effects on lipid and carbohydrate metabolism disorders as found with other legumes. Rats fed a diet enriched with coconut oil (25%) and cholesterol (1%) for 42 days (HH) showed a situation of type IIa hyperlipoproteinemia. However, these lipid alterations were improved in the hypercholesterolemic rats receiving control (HC) and legume (HL) diets for 16 days. Moreover, results confirm that the chickpea was more effective than the control diet containing casein in the normalization of triglycerides as well as total and LDL-cholesterol levels. On the other hand, the HH group showed a marked reduction in the liver glycogen content and Glucose-6-Phase activity (involved in glyconeogenesis) and an increase in Glucokinase (GK) activity (involved in glucose utilization). In contrast, the rats receiving chickpea re-established the liver glycogen deposition as compared to the HH group. Also, the chickpea intake increased the GK activity as compared to the control diet. The overall results support that chickpea intake may be recommended in humans with altered lipid profile such as type IIa hyperlipoproteinemia. Additionally, data concerning carbohydrate utilization indicated its potential positive effects in diabetes therapy and their role as biological active food supplements.

Inclusion of a legume in a saturated fat-rich diet affects the cholesterol status but not the expression of triiodothyronine and retinoic acid receptors in rat liver.

In a previous study, we showed that a high-fat diet, rich in saturated fatty acids and cholesterol, induced hypercholesterolemia and, in rat liver, a decreased expression of TR and RAR, nuclear receptors which are transcription factors for genes involved in cell growth, differentiation and cellular homeostasis. The aim of this study was to determine whether hypercholesterolemia plays a role in the onset of this decreased expression. Rats were fed a high-fat diet, rich in saturated fatty acids and cholesterol, for 3 weeks and then received in addition Vicia faba for 2 weeks. The inclusion of the legume induced a decrease in hypercholesterolemia (in agreement with numerous data) but did not affect the underexpression of TR or RAR (expression evaluated as the maximum binding capacity of receptors and as the abundance of mRNA of these receptors). Thus, it is suggested that, at least in this experimental model, hypercholesterolemia plays a minor role in the decreased expression of nuclear receptors in rat liver.

Expression of retinoic acid, triiodothyronine, and glucocorticoid hormone nuclear receptors is decreased in the liver of rats fed a hypercholesterolemia-inducing diet.

Several studies have shown that dietary factors modulate cell signaling pathways. The aim of this study was to determine whether a hypercholesterolemia-inducing diet rich in saturated fat and cholesterol modifies rat liver expression of the nuclear receptors of retinoic acid (RAR), triiodothyronine (TR), and glucocorticoid hormone (GR), which are transcriptional factors. The experimental diet contained coconut oil 25 g/100 g as a source of lipids, cholesterol 1 g/100 g, and cholic acid 0.5 g/100 g, and the control diet contained olive oil 5 g/100 g. After 26 days of feeding the hypercholesterolemia-inducing diet, a lower binding capacity of the nuclear receptors and a smaller amount of their mRNA were observed. Moreover, the activities of malic enzyme (ME) and tyrosine aminotransferase (TAT), whose gene promotors contain a response element to TR and GR, respectively, were significantly decreased. These changes occurred in a cellular environment characterized by a high level of cholesterol and free fatty acids (FFAs). Thus, two nonexclusive hypotheses can be proposed to explain this decreased expression of nuclear receptors, one emphasizing the effect of lipidic components on the cellular amount of receptor ligands (retinoic acid [RA] and triiodothyronine [T3]), the other emphasizing a modification of the balance between nuclear receptors that could impede the upregulation of TR and RAR.

Aging decreases retinoic acid and triiodothyronine nuclear expression in rat liver: exogenous retinol and retinoic acid differentially modulate this decreased expression.

The expression of nuclear receptors of retinoic acid (RAR) and triiodothyronine (TR) was analyzed in the liver of rats aged 2.5 (young), 6 (adult) and 24 (aged) months. In aged rats, decreased binding properties, binding capacity (Cmax) and affinity (Ka), of nuclear receptors were observed. This resulted, at least in part, from decreased transcription of receptor genes in that the amount of their mRNA also decreased. Moreover, the activity of malic enzyme (ME) and tissue transglutaminase (tTG), whose genes are TR and RAR responsive, respectively, was reduced in aged rats. These results are in agreement with the decreased binding capacity of these receptors. An inducer-related increase of RAR and TR expression was observed 24 h after a single dose of retinoic acid administration (5 mg/kg), while retinol administration (retinyl palmitate, 13 mg/kg) was without incidence on nuclear receptor expression in aged rats.