Resistin mRNA Levels Research Articles

지방세포 3T3-L1에 인삼 사포닌 Re와 의이인 추출액 처리시 비만관련 유전자인 TNF-α, lipoprotein lipase, leptin 및 resistin 발현 조절에 미치는 영향

In order to determine if the mRNA and protein expression levels of 3T3-L1 adipocytes are influenced by oriental medicines, adipocytes were treated with 100 ㎍/ml of G-Re and aqueous extract of a Coix lachrymajobi var. mayuen (AEC) every other day for 12 days, respectively. The tumor necrosis factor alpha (TNF-α). mRNA and protein expressions were suppressed markedly in treated mature adipocytes. Those of lipoprotein lipase (LPL) levels were found to increase gradually in preadipocytes differentiating into mature adipocytes. Those were higher than that of the untreated mature adipocytes. The treated adipocytes showed reduction of leptin expression levels, while in untreated mature adipocytes cell, those of levels were significantly higher after the conversion of preadipocytes into mature adipocytes. The resistin levels in the treated adipocytes were significantly decreased comparing to that of the untreated mature adipocytes. In conclusion, the expression levels of LPL, TNF-α, leptin and resistin mRNA and proteins are shown to be regulated by G-Re and AEC, making them potential candidates for controlling fat mass related obesity.

Conjugated linoleic acid down-regulates expression of resistin and adiponectin in fully differentiated 3T3-F442A cells

Conjugated linoleic acid (CLA) is a naturally occurring derivative of linoleic acid found in dairy products [1]. Dietary supplementation of CLA is known to have several beneficial health effects as an anti-carcinogenic, anti-atherogenic, hypocholesterolemic, anti-diabetic and antiobesity agent [2–5]. Adipose tissue produces a variety of factors, which contribute to insulin resistance characteristic of obesity and obesity-linked type 2 diabetes [6–7]. To explore the possible molecular link between CLA and its anti-diabetic effects, we studied the mRNA expression levels of several molecular markers of diabetes following exposure to CLA [8–11]. Fully differentiated 3T3-F442A cells were treated either by supplement with CLA or linoleic acid (LA, positive control), (100 μm) or untreated (negative control) for 24 h. Subsequently, total RNA was extracted and transcript levels of resistin, adiponectin and PPARγ were assayed by quantitative RT-PCR and normalized to GAPDH (house keeping gene). Supplementation of CLA significantly down-regulated the mRNA levels of resistin and adiponectin (to 20 and 30%, respectively), as compared to LA and untreated-control adipocytes (Fig. 1a, b). PPARγ mRNA levels did not change significantly following CLA supplementation (Fig. 1c). The present results indicate that CLA supplementation down-regulates both resistin and adiponectin, adipockines known to either ameliorate or deteriorate insulin sensitivity, respectively. Further work is currently underway. Fig. 1 Effect of linoleic and CLA treatment on resistin, adiponectin, and PPARγ mRNA levels in 3T3-F442A adipocytes. Confluent 3T3-F442A cells were induced to differentiate as described in “Materials and methods”. At day 10 of differentiation ...

REGULATORY EFFECTS OF ESTROGEN AND PROGESTERONE ON THE ADIPOSE RESISTIN EXPRESSION

Resistin, a hormone secreted by adipocytes, is suggested to be an important link between obesity and diabetes. In addition, resistin gene expression increases during adipogenesis, and its serum levels are elevated in both genetically or diet-induced obese mice. To elucidate the role of resistin, the endocrine mechanisms that regulate resistin expression will be remarkable. Several studies revealed that resistin expression is regulated by hormone, including glucocorticoids, endothelin-1, etc. Gender difference in resistin expression was also reported, the expression was higher in male than female mice, and was significant enhanced after testosterone treatment in males, but not in females. In addition to resistin, estrogen has been implicated in the regulation of adipocytokines expression and secretion. Progesterone is another sex hormone possessing pivotal physiological functions in estrus cycle. A cluster of studies strongly indicated the regulatory effect of progesterone on estrogen action in various aspects, including neuro-protection, vasodilatation, and carbohydrate metabolism. We hypothesized that the resistin expression is co-regulated by both estrogen and progesterone. The aim of this study was to evaluate the regulatory effect of estrogen and progesterone on adipocyte resistin gene expression in ovariectomized (OVX) rats, isolated rat adipocytes and 3T3-L1 adipocytes in vitro. Our preliminary results show that subcutaneous injection of estradiol benzoate (EB) reduced resistin mRNA levels in adipocytes isolated from the inguinal, parametrial, perirenal, retroperitoneal, or periovarian fat deposits of OVX rats, while an in vitro study showed that estradiol treatment decreased resistin mRNA levels in cultured rat adipocytes. Both in vivo and in vitro studies show that progesterone (P4) has no regulatory effect on resistin mRNA expression in rat adipocytes. In 3T3-L1 adipocytes, both EB and P4 have no effect on resistin mRNA expression. These data suggest that estrogen is a pivotal regulator of resistin gene expression. The underlying mechanism mediate EBregulated resistin expression will be explored in the further studies. (poster)

Effect of PPAR-δ agonist on the expression of visfatin, adiponectin, and resistin in rat adipose tissue and 3T3-L1 adipocytes

It has been recently reported that activation of PPAR-δ, by specific agonists or genetic manipulation, alleviates dyslipidemia, hyperglycemia, and insulin resistance in animal models of obesity and type 2 diabetes. The purpose of the present study was to determine whether the PPAR-δ agonist has a direct effect on adipokines in visceral adipose tissue of rats and in cultured adipocytes. We examined the expression of visfatin, adiponectin, and resistin mRNA in visceral adipose tissue of Wistar rats fed a high-fat diet and 3T3-L1 adipocytes treated with PPAR-δ agonist (L-165041). Body weight and biochemical measurements were performed.Rats fed a high-fat diet showed a greater increase in body weight than those fed a standard diet (P<0.05), and treatment with L-165041 (10mg/kg/day) significantly decreased weight gain (P<0.05). The concentration of total cholesterol was lower, and HDL cholesterol was higher in L-165041-treated rats (P<0.05). In the visceral adipose tissue of L-165041-treated rats, visfatin and adiponectin mRNA levels significantly increased compared to those of the untreated rats (P<0.05). However, the expression of resistin decreased in the L-165041-treated rats. Furthermore, in cultured 3T3-L1 adipocytes, the level of visfatin and adiponectin mRNA was up-regulated in response to L-165041 treatment for nine days. By contrast, resistin mRNA levels were down-regulated by L-165041 treatment. The present study provides a novel evidence to suggest that the PPAR-δ agonist has regulatory effects on a variety of adipokines, and these effects might explain some of their metabolic function.

A novel role for Oct-2 in the lipopolysaccharide-mediated induction of resistin gene expression in RAW264.7 cells

Although resistin was first suggested as a possible link between obesity and diabetes, we have demonstrated previously that expression of resistin is induced by LPS (lipopolysaccharide). In the present study, we showed that LPS increased levels of resistin mRNA and promoter activity in murine RAW264.7 macrophages. Investigation of cis-regulatory elements in the mouse resistin promoter required for LPS-mediated induction showed that an Octamer (ATTTGCAT) element, located at -914 to -907, was required for maximal promoter activity in response to LPS stimulation. Co-transfection of RAW264.7 cells with a resistin promoter-luciferase construct and an Oct-1 or Oct-2 expression plasmid (pCG-Oct-1 or pCG-Oct-2) showed that Oct-2, but not Oct-1, activated the resistin promoter upon LPS treatment. Binding of Oct-2 to the Octamer element was demonstrated by supershift DNA-affinity precipitation and chromatin immunoprecipitation assays. Reverse transcription-PCR and Western blot results showed that levels of Oct-2 mRNA and protein were both up-regulated by LPS in RAW264.7 cells. The LPS-induced increase in Oct-2 protein was inhibited by LY294002 (a phosphoinositide 3-kinase inhibitor) post-transcriptionally, and the inhibition also resulted in a lower response of both resistin mRNA and promoter activity to LPS treatment. Moreover, specific knockdown of Oct-2 by RNA interference impaired the LPS-induced increase in resistin mRNA and promoter activity. Together, these results indicate that Oct-2 is involved in the LPS-mediated induction of resistin gene expression in macrophages and suggest that activation of Oct-2 is a part of LPS signalling pathways in macrophages.

Adipocyte resistin mRNA levels are down-regulated by laparoscopic ovarian electrocautery in both obese and lean women with polycystic ovary syndrome

The aim of this study was to investigate serum and adipocyte mRNA expression of resistin in lean and obese women with polycystic ovary syndrome (PCOS) before and 3 months after laparoscopic ovarian electrocauterization (LOE). Adipose tissue obtained from 12 women with PCOS (six obese and six lean, body mass index > 27 kg m(-1) as threshold point) before and after LOE was analysed. Gene expression of resistin was measured by semi-quantitative RT-PCR. Ten lean, age-matched healthy women served as controls. Both lean and obese women with PCOS had significantly higher fasting and 2 h insulin and homeostasis model insulin resistance index (HOMA(IR)) values and lower fasting glucose-to-insulin ratios (G(0)/I(0)) than did the controls. The serum levels of glucose and insulin and HOMA(IR) were significantly decreased, and the G(0)/I(0) ratio was significantly increased 3 months after LOE. No difference was found in serum resistin levels between controls and either obese or lean women with PCOS before LOE, nor between PCOS patients before and after LOE. However, resistin mRNA expression levels in both lean and obese women with PCOS before LOE were significantly higher than that in controls and were decreased significantly after LOE back to control levels. Local resistin activity may be actively involved in the pathogenesis of PCOS. LOE reduces insulin resistance and down-regulates resistin mRNA expression in lean and obese women with PCOS.

Depot-specific messenger RNA expression of 11β-hydroxysteroid dehydrogenase type 1 and leptin in adipose tissue of children and adults

To compare expression of messenger RNA (mRNA) coding for the cortisol regenerating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), and the adipocytokines leptin and resistin in paired biopsies of subcutaneous adipose tissue (SC) and omental adipose tissue (OM) from children. Paired biopsies (SC and OM) were obtained from 54 children (age 0.17-16 years, body mass index (BMI) 12.5-28.3 kg/m(2), BMI standard deviation score (SDS) -2.5-4.5) and 16 adults (age 27-79 years, BMI 19-46 kg/m(2)) undergoing open abdominal surgery. mRNA levels of 11beta-HSD1, leptin and resistin were measured using quantitative real-time polymerase chain reaction (PCR). 11beta-HSD1 mRNA level was higher in OM than in SC (P<0.05), whereas leptin mRNA was higher in SC than in OM (P<0.001). There was no difference in the resistin mRNA level between SC and OM. These results were consistent in children and adults. In children, 11beta-HSD1 mRNA in SC was positively associated with BMI SDS (P<0.05), whereas in OM it was positively associated with age (P<0.05). The association between 11beta-HSD1 expression and age remained significant after adjustment for BMI SDS and gender. Leptin mRNA was positively associated with BMI SDS (SC: P<0.001, OM: P<0.001) but not with age in children. In multiple regression analyses, including anthropometric variables and age, BMI SDS was independently associated with mRNA levels of 11beta-HSD1 (P<0.05) and leptin (P<0.001) in SC. When normal weight and overweight children were analyzed separately, 11beta-HSD1 mRNA levels were positively associated with leptin in OM in the overweight group (P<0.05). There are depot-specific differences in mRNA levels of 11beta-HSD1 and leptin in children and adults. The positive association of 11beta-HSD1 mRNA in OM with age may reflect a causal role in visceral fat accumulation during growth. Increasing 11beta-HSD1 and leptin mRNA in SC with increasing BMI SDS could suggest that the risk of metabolic consequences of obesity may be established early in life.

17β-Estradiol Stimulates Resistin Gene Expression in 3T3-L1 Adipocytes via the Estrogen Receptor, Extracellularly Regulated Kinase, and CCAAT/Enhancer Binding Protein-α Pathways

Resistin is known as an adipocyte-specific secretory hormone that can cause insulin resistance and decrease adipocyte differentiation. It can be regulated by sexual hormones, but the mechanism of estrogen's actions is still not clear. Using 3T3-L1 adipocytes, we found that 17 beta-estradiol (E2) up-regulated resistin mRNA expression in a dose- and time-dependent manner. The concentration of E2 that increased resistin mRNA levels by 100-250% was approximately 1 nM for a range of 1-24 h of treatment. Treatment with either actinomycin D or cycloheximide prevented E2-stimulated resistin mRNA expression, suggesting that the effect of E2 requires new mRNA and protein synthesis. Although E2 was shown to increase activities of the estrogen receptor (ER) and MAPK kinase 1 and the association of nuclear ER alpha and CCAAT/enhancer binding protein-alpha with the resistin gene promoter, signaling was demonstrated to be blocked by pretreatment with either ICI182780 or PD98059. Neither SB203580 nor LY294002 changed the E2-increased levels of resistin mRNA, but they respectively inhibited E2-stimulated phosphorylation of p38 MAPK and Akt. These results imply the ER alpha, ERK, and CCAAT/enhancer binding protein- are necessary for the E2 stimulation of transcription from the resistin promoter. Moreover, PD98059, but not SB203580 or LY294002, antagonized E2-increased resistin protein release. These data suggest that E2 likely modifies the distribution of the resistin protein between the intracellular and extracellular compartments via an ERK-dependent pathway.

Resistin as a putative modulator of insulin action in the daily feeding/fasting rhythm

Resistin and adiponectin are adipokines with postulated opposite functions. Resistin has been related with insulin resistance in obesity, while adiponectin could be associated to higher insulin sensitivity. We have determined whether the production of these two adipokines during the day is related to the feeding rhythm in rats. Resistin mRNA levels in adipose tissue correlated positively with the gastric contents and serum insulin concentration, showing higher levels during the dark phase (period of the highest food intake), especially in the mesenteric depot, while levels decreased during the light phase. The diurnal pattern of resistin expression was not directly reflected in the circulating levels, but it showed a 6-h delay and correlated negatively with the gastric contents and serum insulin. Adiponectin expression followed an opposite pattern, not apparently related to feeding or insulin release, and not translated into changes in circulating levels. Moreover, considering that insulin stimulates resistin expression and that circulating resistin follows a contrary circadian pattern in comparison to insulin, resistin, apart from its role in the increased insulin resistance associated to obesity, could also act as a putative modulator of insulin in the daily feeding/fasting rhythm through a negative feedback regulation of its action.

Tu-P10:457 Inflammatory markers and carotid intima media thickness (C-IMT) in stable IHD patients

Resistin is involved in the inflammatory response, as well as in insulin resistance. In rodents, resistin levels are partially regulated by ovarian hormones. Thus, ovariectomy-induced changes in resistin levels and their response to lipopolysaccharide (LPS)-induced septic stress were evaluated. Ovariectomized (OVX) rats exhibited higher serum resistin concentrations and visceral and subcutaneous white adipose tissue (WAT) resistin mRNA levels than sham-operated (sham) rats under the saline-injected (basal) conditions. The serum resistin levels of the gonadal intact male rats were higher than those of the sham rats, whereas the serum resistin levels of the male and OVX rats did not differ. In both the sham and OVX rats, the serum resistin concentration and the resistin mRNA levels of WAT were increased by LPS injection. At 24 h after the LPS injection, no difference was detected in the serum resistin concentrations or WAT mRNA resistin levels between the sham and OVX rats. These results suggest that ovarian hormones partially regulate the basal resistin levels of female rats.

Increased plasma levels of adipokines in preeclampsia: relationship to placenta and adipose tissue gene expression

Adipokines are predominantly secretory protein hormones from adipose tissue but may also originate in placenta and other organs. Cross-sectionally, we monitored maternal plasma concentration of adiponectin, resistin, and leptin and their mRNA expression in abdominal subcutaneous adipose tissue and placenta from preeclamptic (PE; n = 15) and healthy pregnant (HP; n = 23) women undergoing caesarean section. The study groups were similar in age and BMI, whereas HOMA-IR tended to be higher in the PE group. In fasting plasma samples, the PE group had higher concentrations of adiponectin (18.3 +/- 2.2 vs. 12.2 +/- 1.1 microg/ml, P = 0.011), resistin (5.68 +/- 0.41 vs. 4.65 +/- 0.32 ng/ml, P = 0.028), and leptin (34.4 +/- 3.2 vs. 22.7 +/- 2.1 ng/ml, P = 0.003) compared with the HP group. Adiponectin and leptin concentrations were still different between PE and HP after controlling for BMI and HOMA-IR, whereas resistin concentrations differed only after controlling for BMI but not HOMA-IR. We found similar mean mRNA levels of adiponectin, resistin, and leptin in abdominal subcutaneous adipose tissue in PE and HP women. When data were pooled from PE and HP women, resistin mRNA levels in adipose tissue also correlated with HOMA-IR (r = 0.470, P = 0.012) after controlling for BMI and pregnancy duration. Resistin mRNA levels in placenta were not significantly different between PE and HP, whereas leptin mRNA levels were higher in PE placenta compared with HP. Thus increased plasma concentrations of adiponectin and resistin in preeclampsia may not relate to altered expression levels in adipose tissue and placenta, whereas both plasma and placenta mRNA levels of leptin are increased in preeclampsia.

Resistin SNP-420 determines its monocyte mRNA and serum levels inducing type 2 diabetes

Resistin, secreted from adipocytes, causes insulin resistance in rodents. Its roles and main source in humans remain unknown. The G/G genotype of resistin single nucleotide polymorphism, SNP-420, induces type 2 diabetes mellitus (T2DM) by increasing promoter activity. We elucidated factors correlated with serum resistin and effects of SNP-420 on monocyte resistin mRNA. In 198 T2DM and 157 controls, fasting serum resistin was higher in T2DM. Multiple regression analysis revealed that SNP-420 genotype was the strongest determinant of serum resistin. In T2DM, 1-year duration of T2DM and 1% HbA1c was also correlated with 0.19 and 0.54 ng/ml serum resistin, respectively. Logistic regression analysis revealed that serum resistin was an independent factor for T2DM. In 23 healthy volunteers, monocyte resistin mRNA was positively correlated with its simultaneous serum levels and was higher in G/G genotype. Thus, SNP-420 determines monocyte mRNA and serum levels of resistin, which could induce T2DM.

Transcriptional regulation of the resistin gene

Resistin, which is a protein that is secreted exclusively by adipocytes, plays an important role in insulin resistance and adipocyte differentiation. Adipocytes express significant amounts of resistin mRNA, while preadipocytes express low levels of resistin mRNA. The mechanism that causes this difference is unclear. Therefore, we studied the mechanism regulating resistin expression and the roles of different transcriptional factors in this process. The results from fluorescent photography and semi-quantitative RT-PCR showed that sterol regulatory element-binding protein 1c (SREBP1c) and cyclic AMP response-element-binding protein (CREB) had no effect on resistin expression. By contrast, CCAAT/enhancer-binding protein-α (C/EBPα) increased resistin mRNA levels both in 3T3-L1 preadipocytes and in 293T cells. The relative increase in the amount of resistin mRNA in the 293T cells was much larger than that in the 3T3-L1 preadipocytes. Moreover, while C/EBPα was necessary for resistin expression, we found that up-regulating C/EBPα levels alone was not sufficient to induce a similar level of resistin in preadipocytes to that in adipocytes.

Differential effects of dietary saturated and trans-fatty acids on expression of genes associated with insulin sensitivity in rat adipose tissue

Trans-fatty acids (TFAs) are formed during partial hydrogenation of vegetable oils and are shown to be more atherogenic than saturated fatty acids (SFAs). Our previous study showed that dietary TFAs decrease adipose tissue insulin sensitivity to a greater extent than SFAs in rats. We hypothesized that the effects of these fatty acids on insulin sensitivity could be mediated through an alteration in gene expression. In the current study we have investigated the effects of dietary TFAs or SFAs on expression of genes associated with insulin sensitivity in rat adipose tissue. Male weanling Wistar/NIN rats were divided into four groups and fed one of the following diets containing 10% fat (g/100 g diet) differing only in the fatty acid composition for 3 months: control diet (3.7% linoleic acid (LA)), SFA diet (5% SFA), TFA diet 1 (1.5% TFA + 1% LA) and TFA diet 2 (1.5% TFA + 2% LA). The mRNA expression of peroxisome proliferator-activated receptor gamma (PPARgamma), lipoprotein lipase (LPL), glucose transporter-4 (GLUT4), resistin and adiponectin was analyzed in epididymal fat using RT-PCR. The effects of TFA were studied at two levels of LA to understand the beneficial effects of LA over the effects of TFA. Both dietary SFA and TFA upregulated the mRNA levels of resistin. Dietary SFA downregulated adiponectin and GLUT4 and upregulated LPL, while TFA downregulated PPARgamma and LPL. The effects of dietary TFA on PPARgamma and resistin were not counteracted by increased LA (TFA diet 2). The effects of SFAs on the aforementioned genes except PPARgamma could be extrapolated towards decreased insulin sensitivity, while only the alteration in the mRNA levels of PPARgamma and resistin could be associated with insulin resistance in TFA-fed rats. These findings suggest that dietary SFAs and TFAs alter the expression of different genes associated with insulin sensitivity in adipose tissue.

The potential role of resistin in atherogenesis

Resistin, an adipocyte-derived cytokine linked to insulin resistance and obesity, has recently been shown to activate endothelial cells (ECs). Using microarrays, we found that along with numerous other pro-atherosclerotic genes, resistin expression levels are elevated in the aortas of C57BL/6J apoE−/− mice; these findings led us to further explore the relation between resistin and atherosclerosis. Using TaqMan PCR and immunohistochemistry, we found that ApoE−/− mice had significantly higher resistin mRNA and protein levels in their aortas, and elevated serum resistin levels, compared to C57BL/6J wild-type mice. Incubation of murine aortic ECs with recombinant resistin increased monocyte chemoattractant protein (MCP)-1 and soluble vascular cell adhesion molecule (sVCAM)-1 protein levels in the conditioned medium. Furthermore, human carotid endarterectomy samples stained positive for resistin protein, while internal mammary artery did not show strong staining. Patients diagnosed with premature coronary artery disease (PCAD) were found to have higher serum levels of resistin than normal controls. In summary, resistin protein is present in both murine and human atherosclerotic lesions, and mRNA levels progressively increase in the aortas of mice developing atherosclerosis. Resistin induces increases in MCP-1 and sVCAM-1 expression in murine vascular endothelial cells, suggesting a possible mechanism by which resistin might contribute to atherogenesis. Finally, PCAD patients exhibited increased serum levels of resistin when compared to controls. These findings suggest a possible role of resistin in cardiovascular disease.

Stimulated resistin expression in white adipose of rats with bile duct ligation-induced liver cirrhosis: relationship to cirrhotic hyperinsulinemia and increased tumor necrosis factor-alpha

Resistin, an adipose-derived polypeptide hormone, is proposed as a candidate of insulin resistance, although its roles in inhibiting adipogenesis and in inflammation have also been suggested. Liver cirrhosis is characterized by elevated circulating proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), hyperinsulinemia and insulin resistance. The study aimed to examine resistin expression and its association with insulin and TNF-α in a cirrhotic rat model using bile duct ligation (BDL). The BDL-induced cirrhotic rats showed significantly lower fat mass, insulin sensitivity and elevated plasma insulin and TNF-α compared to sham animals. In addition, epididymal TNF-α and resistin mRNA and protein levels were higher in cirrhotic rats. In normal control rats, in vivo insulin infusion and ex vivo administration of TNF-α to cultured fat pads increased resistin gene expression significantly. These results implied that hyperinsulinemia and increased TNF-α levels might upregulate adipose resistin gene in BDL-induced liver cirrhosis. Further study is necessary to document the role of resistin in metabolic abnormalities of liver cirrhosis.

Resistin expression in 3T3-L1 adipocytes is reduced by arachidonic acid

The resistin gene is expressed in adipocytes and encodes a protein proposed to link obesity and type 2 diabetes. Increased plasma FFA is associated with insulin resistance. We examined the effect of separate FFAs on the expression of resistin mRNA in cultured murine 3T3-L1 adipocytes. The FFAs tested did not increase resistin expression, whereas both arachidonic acid (AA) and eicosapentaenoic acid (EPA) reduced resistin mRNA levels. AA was by far the most potent FFA, reducing resistin mRNA levels to approximately 20% of control at 60-250 muM concentration. Selective inhibitors of cyclooxygenase-1 and of mitogen-activated protein kinase kinase counteracted AA-induced reduction in resistin mRNA levels. Transient overexpression of sterol-regulatory element binding protein-1a (SREBP-1a) activated the resistin promoter, but there was no reduction in the abundance of approximately 65 kDa mature SREBP-1 after AA exposure. Actinomycin D as well as cycloheximide abolished the AA-induced reduction of resistin mRNA levels, indicating dependence on de novo transcription and translation. Our data suggest that reductions in resistin mRNA levels involve a destabilization of the resistin mRNA molecule. An inhibitory effect of AA and EPA on resistin expression may explain the beneficial effect of ingesting PUFAs on insulin sensitivity.

Resistin mRNA levels are downregulated by estrogen in vivo and in vitro

Resistin, a hormone secreted by adipocytes, is suggested to be an important link between obesity and diabetes. The aim of this study was to evaluate the regulatory effect of estrogen on adipocyte resistin gene expression in ovariectomized (OVX) rats and in isolated rat adipocytes in vitro. Subcutaneous injection of estradiol benzoate reduced resistin mRNA levels in adipocytes isolated from the inguinal, parametrial, perirenal, retroperitoneal, or periovarian fat deposits of OVX rats, while an in vitro study showed that estradiol treatment decreased resistin mRNA levels in cultured rat periovarian fat adipocytes. Results of Western blotting analysis also showed that estrogen decreased adipose resistin contents in vivo and in vitro. These data suggest that estrogen is a pivotal negative regulator of resistin gene expression.

Expression of resistin mRNA in adipose tissue of rat model with polycystic ovarian syndrome and its implication.

To investigate the relationship between the insulin resistance (IR) of polycystic ovarian syndrome (PCOS) rat model induced by dehydroeplandrosterone (DHEA) and hormonal changes in the ovarium and the resistin mRNA levels in adipose tissue, 21-day-old female SD rats were divided into two groups in pairs. The rats in group 1 were injected daily (s.c.) with DHEA for up to 20 days and the rats in group 2 injected with oil at the same time. Ovarian weight, serum insulin levels and sex hormone levels in rat blood of both groups were determined. Oral glucose tolerance tests, light microscopic and electronic microscopic examination were performed. The levels of resistin mRNA in adipose tissue were measured by reverse transcription-polymerase chain reaction (RT-PCR). Our results showed that the ovarian weight in group 1 was greater than that in group 2 (P<0.05). The ovaria in group 1 showed multiple follicular cysts, The serum testeosterone and etrasdiol concentration were significantly higher in group 1 than those in group 2 (P<0.001 and P<0.05 respectively), so as the fasting serum glucose (P<0.001) and fasting serum insulin (P<0.05). The value of 1/FINS x FGC was significantly higher in group 1 than that in group 2 (P<0.001). Moreover, the resistin mRNA level of white adipose tissue in the DHEA-induced group was significantly higher than that in the control rats (P<0.05). It is concluded that the DHEA-induced PCOS rat models were similar to those of the patients with PCOS, and the IR was observed. Resistin secreted by adipose tissue may mediate IR in PCOS, and it is likely involved in the pathogenesis and development of PCOS.

Genome-wide scan of resistin mRNA expression in omental adipose tissue of baboons.

The hormone resistin was recently discovered in adipose tissue of mice. Functional tests suggest a role for resistin in the regulation of insulin sensitivity. However, human studies have reported controversial results on the metabolic function of this hormone. A 1 g omental adipose tissue biopsy was obtained from 404 adult baboons. Resistin mRNA expression was assayed by real-time, quantitative RT-PCR, and univariate and bivariate quantitative genetic analyses were performed, via the variance decomposition approach. A genome scan analysis was conducted using resistin mRNA abundance in omental adipose tissue as a quantitative phenotype. A significant heritability of h2 = 0.23 (P = 0.003) was found for resistin mRNA abundance in omental adipose tissue. A genome scan detected a quantitative trait locus for resistin expression with an LOD score of 3.8, in the region between markers D19S431 and D19S714, corresponding to human chromosome 19 p13. This chromosomal region contains genes related to insulin resistance phenotypes, such as resistin, insulin receptor, angiopoietin-like 4 protein and LDL receptor. Individual variation in resistin mRNA expression has a significant genetic component, and a gene or genes on chromosome 19 p13 may regulate resistin mRNA levels in baboon omental adipose tissue.