mRNA Expression Levels Of Leptin Research Articles

Bidirectional regulation of BDE-47 on 3T3-L1 cell differentiation based on a restricted cubic spline model.

BDE-47 (2,2,4,4-tetrabromodiphenyl ether) is a polybrominated diphenyl ether (PBDE) congener, which has the characteristics of high biological detection rate, the highest content and strong biological toxicity, and is widely distributed in organisms. Many studies have found that BDE-47 may also be an environmental risk factor for metabolic diseases such as obesity, insulin resistance, type 2 diabetes, and hypertension. However, the way that PBDEs influence adipocyte differentiation remains unclear. The methylisobutylxanthine, dexamethasone, and insulin method was used to study the effect of BDE-47 on the differentiation of 3T3-L1 cells. The 3T3-L1 cells were exposed by different concentrations of BDE-47, and the effect of cell viability was detected at different stages. In addition, the lipid droplet aggregation of adipocytes was observed and the triglyceride (TG) levels in the cytoplasm were detected after differentiation. The relative mRNA expression levels of leptin, adiponectin, and PPARγ in cells were determined by RT-PCR, and differentially expressed genes were preliminarily screened by digital gene expression profile. Our study found that BDE-47 promoted the differentiation of 3T3-L1 cells. Restriction cubic spline analysis showed that BDE-47 bidirectionally. regulated the mRNA synthesis of TG, PPARγ, and leptin genes and the aggregation of lipid droplets. BDE-47 may induce adipocyte differentiation by activating PPARγ, resulting in the differential expression of genes related to the AMPK signaling pathway, insulin resistance, and other metabolic pathways. The highest and lowest-dose BDE-47 exposure groups had the greatest impact on adipocyte differentiation.

187P Development of a magnetic nanostructure for co-delivery of metformin and silibinin on growth of lung cancer cells: Possible action through leptin gene and its receptor regulation

Chemotherapeutic combinational approaches would be more efficient in decreasing toxicity of drug, preventing tumor progression in relation to either drug alone. Hence, the aim of this study was to construct magnetic PLGA/PEG nanoparticles (NPs) co-loaded with metformin (Met) and silibinin (Sil) to investigate their cytotoxicity as well as their impact on mRNA expression levels of leptin and leptin receptor genes in A549 lung cancer cells.

Development of a Magnetic Nanostructure for Co-delivery of Metformin and Silibinin on Growth of Lung Cancer Cells: Possible Action Through Leptin Gene and its Receptor Regulation.

Objective:Chemotherapeutic combinational approaches would be more efficient in decreasing toxicity of drug, preventing tumor progression in relation to either drug alone. Hence, the aim of this study is to constract magnetic PLGA/PEG nanoparticles (NPs) co-loaded with Metformin (Met) and Silibinin (Sil) to investigate their cytotoxicity as well as their impact on mRNA expression levels of leptin and leptin receptor genes in A549 lung cancer cells. Materials and Methods:The synthesized NPs were characterized by FTIR, FE-SEM, and VSM and then, MTT assay was utilized to assess and compare the cytotoxicity of various concentrations of the chemotheruptic molecules in pure and nanoformulated forms as well as in alone and combination state after 48 h exposure time. Moreover, the mRNA levels of leptin and its receptor genes expression were studied by quantitative real-time PCR. By co-encapsulation of Met and Sil into PLGA/PEG/ Fe3O4, cytotoxic efficiency of the compounds considerably augmented for all concentrations. Results:Cytotoxicity assay displayed that combination of Met and Sil had a synergistic concentration-dependent effect on A549 lung cancer cells. Moreover, qPCR data revealed that the expression levels of the leptin and leptin receptor was considerably reduced with increasing concentrations of drug-encapsulated magnetic NPs, especially Met/Sil-encapsulated PLGA/PEG/ Fe3O4 NPs. Conclusion:Present preliminary study shows that co-incorporating Met, Sil, Fe3O4 into PLGA/PEG NPs might provide a more promising and safe treatment strategy for lung cancer.

Zhuang-Gu-Fang Treats Osteoporosis in Ovariectomized Rats by Increasing the Osteogenesis-Related Factors Leptin, Ghrelin, and PYY.

Zhuang-Gu-Fang is a Chinese medicinal compound mixture, which is mainly composed of traditional remedies like the Epimedium Herb, Astragalus, and Eucommia among many others. The study is aimed at investigating the therapeutic effect of Zhuang-Gu-Fang in ovariectomized rats. Fifty six-month-old Wistar rats were randomly selected and divided into 5 groups (n = 10), namely, model group, positive group, low-dose Chinese medicine group, medium-dose group, and high-dose group. Another 10 sham operation Wistar rats were taken as a negative control group. After 3 months of intervention, the bone mineral density (BMD), procollagen type I N-peptide (PINP), beta C-terminal cross-linked telopeptides of type I collagen carboxyl-terminal peptide (β-CTX), Leptin, Ghrelin, and Peptide YY (PYY) of each group were measured. Besides, the ultrastructure of bone structure and osteoblasts was also observed by transmission electron microscopy. Western blot method was used to detect the expression levels of Leptin and Ghrelin in bone tissue, and RT-PCR detected the mRNA expression levels of Leptin and Ghrelin. BMD test indicated that Zhuang-Gu-Fang could effectively prevent the loss of tibia bone in ovariectomized rats. Histomorphology analysis showed that Zhuang-Gu-Fang could preserve trabecular bone structure integrity and improve osteoblast ultrastructure. Notably, the study found out that Zhuang-Gu-Fang worked through balancing the bone metabolism via increasing bone formation/resorption ratio. Additionally, Zhuang-Gu-Fang highlighted the recovery effects in multiple levels of osteogenesis- and osteanagenesis-related factors Leptin, Ghrelin, and PYY. Conclusively, the study proved the therapeutic potential of the Zhuang-Gu-Fang for postmenopausal osteoporosis (PMOP) and further revealed that its therapeutic effect was related to the balance of bone metabolism and the recovery effects of bone-related factors Leptin, Ghrelin, and PYY.

Role of diet on intestinal metabolites and appetite control factors in SD rats.

The present study aimed to investigate changes in the levels of metabolites and appetite control factors caused by different dietary interventions in Sprague Dawley (SD) rats. A total of 35 male SD rats were weaned and immediately randomly assigned to five groups. The control group was given ad libitum access to a normal chow diet, and the other groups received a high-fat diet (FAT group), high-sugar diet, high-fibre or high-protein diet (PRO group) for 4 weeks. The high-fat diet contributed to weight gain and adipose tissue formation, and affected lipid indexed. The FAT group had a higher body weight, Lee's index, adipose mass and glucose tolerance than all of the other groups. The opposite effect was observed in the PRO group. High-performance liquid chromatography revealed that short-chain fatty acid and amino acid formation were affected by the various diets. In addition, differences in the mRNA expression levels of leptin, ghrelin and associated receptors were determined in the gastrointestinal, adipose and hypothalamus tissues. The present study provides further evidence of the role of diet in obesity development and prevention. It also highlights the role of intestinal metabolites and appetite control factor expression in the pathogenesis of obesity in SD rats.

Assessment of expression levels of leptin and leptin receptor as potential biomarkers for risk of prostate cancer development and aggressiveness.

BackgroundProstate cancer (PCa) is one of the most frequently diagnosed cancers worldwide. Despite the growing evidence associating obesity and adipokines, particularly leptin and its receptors, with cancer development and progression, it is still a debatable matter in PCa.ObjectivesWe aimed to assess the role of leptin and its receptors as potential biomarkers for the risk of PCa development and aggressiveness.MethodsIn this study, 176 men were included and categorized according to an established histopathological diagnosis into three age‐ and BMI‐matched groups. The PCa group included 56 patients while the BPH group and the control group comprised 60 men each. Serum levels of total PSA (tPSA) were assessed by ELISA and mRNA expression levels of leptin and leptin receptors were assessed by RT‐PCR.ResultsLeptin and leptin receptor mRNA expression levels were significantly higher in PCa patients relative to BPH and to healthy control men. Both were overexpressed in PCa patients with aggressive and distantly metastasizing tumors compared to patients with confined tumors. Leptin receptor mRNA was an independent predictor of high Gleason score ≥ 7, distant metastasis, LN, and seminal vesicles invasion.ConclusionLeptin and its receptors are suggested to be potential biomarkers for PCa; leptin receptor mRNA might predict risk and aggressiveness of PCa.

Effects of Cyclocarya paliurus polysaccharide on lipid metabolism-related genes DNA methylation in rats

The present study was conducted to evaluate the effect of CPP on the DNA methylation and expressions of lipid metabolism-related genes (leptin and MTTP) in hyperlipidemic rats. After 8 weeks intervention of CPP, the abdominal wall fat index, liver weight, the serum concentrations of TC, TG and LDL-C were significantly decreased, while HDL was increased. In addition, DNA methylation was analyzed by bisulfite sequencing method, and the mRNA expression levels of leptin and MTTP were detected by Q-PCR. The results showed that CPP could considerably decrease DNA methylation levels of leptin (regions from −694 ~ −370 bp contains 14 CpGs and –324 ~ −29 bp contains 18 CpGs) and MTTP (region from −350 ~ −1 bp contains 11 CpGs) promoters in the liver with the maximum decrease rate of 43.2%, 40.2% and 7.7%, respectively. In parallel, the mRNA contents of leptin and MTTP were dramatically down-regulated. In conclusion, the present findings demonstrated that CPP can regulate the level of mRNA by controlling DNA methylation levels in the liver, thereby reducing blood lipids.

Pharmacological Mechanisms of Boiogito and Bofutsushosan in Diabetes and Obesity Models

The antihyperglycemic activities of extracts of boiogito (BOT) and bofutsushosan (BTS) were investigated in streptozotocin-induced (STZ)-diabetic mice. BOT extract containing Stephania tetrandra S. MOORE root (stephania), has more potent antihyperglycemic activity than BOT extract containing sinomenium stem (sinomenium). Extracts of stephania and astragalus root (astragalus) exert combined effects in the antihyperglycemic and insulinotropic activities of BOT extract. Fangchinoline, but not tetrandrine, in stephania plays a role in its activity. Formononetin in astragalus potentiates the actions of fangchinoline. Tetrandrine has antiangiogenic effects on choroidal vessels in STZ-diabetic rats, which are associated with the inhibition of tumor necrosis factor (TNF)-α-induced nuclear factor (NF)-κB activation. BTS extract has shown antihyperglycemic and insulinotropic activities whereas gardenia fruit (gardenia) extract in BTS has antihyperglycemic, but not insulinotropic, activity in the diabetic mice. Gardenia extract decreased the HOMA-IR level and increased insulin-stimulated 2-deoxyglucose (2-DG) uptake to skeletal muscle. The effects of gardenia extract on 2-DG uptake were associated with the upregulation of glucose transporter type 4 and Akt phosphorylation. Gardenia extract was also shown to have antihyperglycemic and insulinotropic actions in high-fat diet (HFD)-fed and STZ-diabetic mice. In addition, gardenia extract decreased the production of TNF-α and leptin, and increased the production of adiponectin in the visceral adipose tissues. In the early administration period, BTS extract increased mRNA expression levels of leptin, adiponectin, and UCP1 in brown adipose tissues in HFD-fed obese mice. With a longer duration of administration, BTS extract improved insulin resistance and subsequently reduced serum leptin and triglyceride levels in parallel with visceral adipose tissue volume and size.

SHORT CHAIN FATTY ACIDS UPREGULATE ADIPOKINE PRODUCTION IN TYPE 2 DIABETES-DERIVED HUMAN ADIPOCYTES.

Short chain fatty acids (SCFAs) play a major regulatory role in adipocyte function and metabolism. The aim of this study was to investigate the effects of SCFAs on adiponectin and leptin expression in adipocytes, and also to determine whether the effects of SCFA treatment in visceral adipocytes obtained from healthy subjects are different relative to the effects in adipocytes from patients with type 2 diabetes. Human pericardiac preadipocytes and human pericardiac preadipocytes type 2 diabetes were differentiated into adipocytes for 21 days in 48-well plates. After differentiation, two kinds of mature adipocytes, human pericardiac adipocytes (HPAd) and human pericardiac adipocytes-type 2 diabetes (HPAd-T2D) were incubated with or without 1 mM of acetic acid (AA), butyrate acid (BA), and propionic acid (PA). After 48 hours of incubation, intracellular lipid accumulation was measured using oil red staining. In addition, mRNA levels of adiponectin, leptin and Peroxisome Proliferator-Activated Receptor γ (PPARγ) were determined by Real-Time PCR system. In HPAd, SCFA supplementation did not inhibit lipid accumulation. By contrast, both AA (p<0.01) and PA (p<0.01) significantly inhibited lipid accumulation in HPAd-T2D. Regarding mRNA levels of adiponectin, no significant changes were found in HPAd, while all three types of SCFAs significantly increased (p<0.05) adiponectin expression in HPAd-T2D. Leptin mRNA expression levels were significantly increased by treatment with all three types of SCFAs in both HPAd (p<0.05) and HPAd-T2D (p<0.05). SCFAs inhibited lipid droplet accumulation and increased mRNA expression of adiponectin and leptin in T2D-derived adipocytes.

Mechanisms for the anti-obesity actions of bofutsushosan in high-fat diet-fed obese mice

BackgroundThe Kampo medicine bofutsushosan (BTS; Pulvis ledebouriellae compositae; Fang Feng Tong Sheng San) has been used as an anti-obesity treatment in overweight patients. In this study, we assessed the underlying physiological changes induced by BTS in obese mice maintained on a high-fat diet.MethodsMale ICR mice were fed a 60% kcal fat diet for 5 weeks starting at 4 weeks of age and then fed the same diet with administration of water (control) or aqueous BTS extract (1.0–2.0 g/kg) for 25 days. Body weight, wet weight of isolated white adipose tissue, and obesity-related serum parameters (glucose, lipids, leptin, adiponectin) were measured after treatment. The mRNA expression levels of leptin, adiponectin, and UCP1 in the adipose tissues were determined by quantitative real-time polymerase chain reaction after the first 5 days of treatment.ResultsBofutsushosan (1.5–2.0 g/kg) significantly decreased total body weight and total wet weight of white adipose tissue isolated from subcutaneous (retroperitoneal) and visceral regions (epididymal, mesenteric, and perirenal). At 2.0 g/kg, BTS also decreased total fat mass, visceral fat mass, and ratio of fat mass to body weight as measured by computed tomography, and significantly decreased epididymal adipocyte size after 14 and 25 days’ treatment. Twenty-five days’ treatment lowered serum glucose, insulin, leptin, and triglycerides, and reduced homeostasis model assessment-insulin resistance. Alternatively, 2.0 g/kg BTS significantly increased mRNA levels of adiponectin, leptin, and UCP1 in interscapular brown adipose tissue but not epididymal white adipose tissue after 5 days’ administration.ConclusionIn the early administration period, BTS increased mRNA expression levels of leptin, adiponectin, and UCP1 in brown adipose tissues. With longer administration, BTS improved insulin resistance, and subsequently reduced serum levels of leptin and triglyceride in parallel with decreased visceral white adipose tissue volume and adipocyte size.

Increased Leptin and Leptin Receptor Expression in Dogs With Gallbladder Mucocele.

BackgroundLeptin and its receptor play a role in several disease processes such as pancreatitis and heart disease. However, their association with gallbladder mucocele (GBM) in dogs has not been reported.Hypothesis/ObjectivesTo evaluate differences in the expression of leptin and leptin receptor between dogs with and without GBM.AnimalsTwenty‐five healthy dogs, including 9 laboratory beagle dogs, and 22 client‐owned dogs with GBM.MethodsSerum leptin concentration was determined in blood samples of all dogs by ELISA. Canine gallbladder samples were collected from 9 dogs with GBM that underwent surgery for therapeutic purposes and from 9 healthy laboratory beagle dogs as a normal control group. Samples were analyzed for leptin and leptin receptor mRNA by real‐time polymerase chain reaction.ResultsSerum leptin concentration was significantly higher in dogs with GBM than in healthy dogs (medians of 7.03 and 2.18 ng/mL, respectively; P < .001). Patients with GBM that had undergone surgery had significantly higher serum leptin concentrations than those that had not (medians of 12.2 and 4.09 ng/mL, respectively; P = .001). However, no difference in serum leptin concentration was found between dogs with GBM with or without endocrinopathies. The mRNA expression levels of leptin and its receptor were significantly increased in the gallbladder tissues of dogs with GBM.Conclusions and Clinical ImportanceDysregulation of leptin might be involved in the pathophysiology of GBM, and leptin concentrations might be associated with GBM severity.

Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1 adipocytes deprived of glucose.

AimsLeptin plays an important role in the pathogenesis of obesity and diabetes, yet the regulatory mechanisms of this hormone have not been fully elucidated. In this study, we aimed to clarify the roles of insulin and glucose in leptin secretion and mRNA production using inhibitors of insulin signal transduction in adipocytes cultured under glucose-free or normal conditions.MethodsDifferentiated 3T3-L1 adipocytes were stimulated with insulin in combination with inhibitors for phosphoinositide 3-kinase (PI3K), Akt, and phosphodiesterase 3B (PDE3B), as well as epinephrine and a cyclic AMP (cAMP) analog under glucose-free or normal conditions. After 8 h of stimulation, leptin protein levels in the media and leptin mRNA expression levels in the adipocytes were measured.ResultsInsulin significantly increased the secretion and mRNA levels of leptin under the depletion of glucose. Glucose augmented basal leptin secretion without insulin, while glucose nullified insulin-induced leptin mRNA upregulation. The PI3K inhibitor BEZ-235, the Akt inhibitor MK-2206, and the PDE3B inhibitor cilostazol attenuated the insulin stimulation of leptin secretion, but did not suppress the insulin-induced leptin mRNA upregulation with glucose depletion. In contrast to the glucose-free condition, insulin failed to upregulate leptin mRNA in the presence of glucose. The cAMP analog dibutyryl cAMP and epinephrine decreased both leptin secretion and mRNA regardless of glucose supplementation.ConclusionInsulin alone stimulates leptin secretion and elevates leptin mRNA levels via cAMP under the lack of glucose metabolism, while glucose is a significant and ambivalent effector on the insulin effects of leptin.

Association between leptin gene expression in subcutaneous adipose tissue and circulating leptin levels in obese patients with psoriasis.

Numerous reports have shown that psoriasis is associated with obesity and leptin. However, few reports are available on the association between serum leptin levels and leptin gene expression in SAT of psoriasis patients. To clarify this point, we examined serum leptin levels and expression levels of leptin messenger RNA (mRNA) in subcutaneous adipose tissue (SAT) of psoriasis patients. 17 psoriasis vulgaris patients and 6 non-obese control patients who underwent skin surgery were enrolled in this study. We measured serum leptin levels. SAT samples in psoriasis patients were taken from beneath the lesional psoriatic skin at the time of skin biopsy. Leptin mRNA expression in SAT was measured using quantitative real-time reverse transcription polymerase chain reaction (real-time RT-PCR) amplification. Leptin mRNA expression showed a positive correlation with serum leptin levels and BMI. We classified psoriasis patients into two groups according to BMI: the group of non-obese psoriasis patients (BMI < 25, n = 7), and the group of obese psoriasis patients (BMI ≥ 25, n = 10). PASI score, serum leptin levels and Leptin mRNA expression in SAT were significantly higher in the obese psoriasis patients than in the non-obese psoriasis patients. Leptin mRNA expression in SAT was correlated with circulating levels of leptin, the severity of psoriasis, and obesity in psoriasis patients. Serum leptin levels and leptin mRNA expression levels in SAT of non-obese psoriasis patients were not significantly different from those of non-obese controls. The altered secretion of leptin by SAT may be related to the severity of psoriasis.

Cloning, tissue distribution and effects of fasting on mRNA expression levels of leptin and ghrelin in red-bellied piranha (Pygocentrus nattereri)

cDNAs encoding the appetite regulating peptides leptin and ghrelin were isolated in red-bellied piranha (Characiforme, Serrasalmidae) and their mRNA tissue and brain distributions examined. When compared to other fish, the sequences obtained for all peptides were most similar to that of other Characiforme fish and Siluriformes. All peptides were widely expressed within the brain and in several peripheral tissues, including gastrointestinal tract. In order to better understand the role of these peptides in the regulation of feeding of red-bellied piranha, the mRNA expression levels of leptin and ghrelin were examined in both brain and intestine, in fed and 7-day fasted fish. No significant differences in expression were seen in whole brain for either peptide. Within the intestine, there was a decrease in leptin mRNA expression and an increase in ghrelin mRNA expression in fasted fish, compared to fed fish. The results suggest that leptin and ghrelin might play a major role in the regulation of feeding and energy homeostasis of red-bellied piranha and this role might be more prominent in the intestine than in the brain.

Increased leptin mRNA expression in the blood of dogs naturally infected by Leishmania infantum

Canine leishmaniosis (CL) is a severe and potentially fatal zoonosis caused by the protozoan Leishmania infantum. Severe forms of CL are commonly associated with a non-protective, humoral immune-response and high parasitic loads. Leptin, a 16 kD hormone mainly secreted by adipocytes, regulates both the innate and adaptive immunity. The goal of this study was to evaluate leptin mRNA expression levels in blood samples from privately owned dogs with CL (n = 11) and healthy controls (n = 10) using quantitative, real-time polymerase chain reaction. Blood samples from dogs with CL expressed significantly higher leptin mRNA levels (two-fold) compared to healthy controls (P = 0.018). The results suggest a possible involvement of leptin in the pathophysiology of Leishmania infection in dogs and the possible use of leptin as a biomarker for CL. Future studies investigating the immunological role of leptin in dogs with CL are warranted.

TCF7L2 and Wnt Signalling Positively Regulate Leptin Gene Expression in Adipocytes

Recent genome-wide association studies (GWAS) have revealed that the Wnt signalling pathway effector TCF7L2 is among the most important diabetes risk genes. Intensive explorations on metabolic function of TCF7L2 in pancreas and liver, however, have generated controversial suggestions. As TCF7L2 is also abundantly expressed in adipocytes, we investigated its expression and function in rodent fat tissue and primary adipocytes. We found that TCF7L2 expression in mouse epididymal fat tissue was physiologically upregulated by feeding, and downregulated in db/db mice and Zucker (fa/fa) rats, 2 obese rodent models. In rat primary adipocytes, 1 nM insulin stimulated TCF7L2 and leptin mRNA expression levels, and the stimulation can be attenuated by iCRT14, an inhibitor of β-catenin-responsive transcription. Insulin at the dosage of 100 nM, however, repressed both TCF7L2 and leptin mRNA levels. The canonical Wnt ligand Wnt3a, but not the non-canonical Wnt ligand Wnt11, was shown to stimulate leptin mRNA expression level and leptin gene promoter activity. Although Wnt3a repressed the differentiation of 3T3-L1 cells toward adipocytes, in either fully differentiated or partially differentiated 3T3-L1 cells, Wnt3a significantly stimulated leptin mRNA levels. Together, our observations suggest that adipocytes TCF7L2 level is metabolic regulated. More importantly, Wnt pathway plays a dual function in adipocytes, including the repression of adipogenesis in pre-adipocytes and the stimulation of leptin production in mature adipocytes, in response to nutritional challenge.

Effect of residual feed intake on hypothalamic gene expression and meat quality in Angus-sired cattle grown during the hot season1,2

The relationship between heat stress, meat quality, and residual feed intake (RFI) is unknown in growing steers. To address this issue, high RFI (HRFI) and low RFI (LRFI) individuals were compared by assessing RFI in 48 Angus-sired steers during a 70-d feeding trial conducted during July through September to identify steers with calculated RFI at least 2 SD apart. The association of RFI with indices of meat quality and expression of genes within hypothalamic and adipose tissue was then determined in LRFI and HRFI steers. While on test, feed intake was recorded daily with BW and hip heights recorded every 14 d. Ultrasound measurements of rib eye area (REA) and backfat (BF) were recorded initially and before harvest. Carcass and growth data were analyzed using a mixed model with RFI level (LRFI and HRFI) as the independent variable. The least square means for RFI were -1.2 and 0.99 kg DMI/d, respectively, for the LRFI and HRFI cohorts (P < 0.0001). Dry matter intake was higher for the HRFI individuals versus the LRFI steers (P < 0.0001) while on-test gain was not different (P < 0.95). Marbling score was greater in LRFI than HRFI steers (P < 0.05). However, there were no differences in REA (P < 0.53), BF (P < 0.65), yield grade (P < 0.24), or objective Hunter color measures between LRFI and HRFI steers indicating there was no consistent relationship between RFI and indices of meat quality. Hypothalamic neuropeptide Y (NPY), agouti related protein (AGRP), relaxin-3 (RLN3), melanocortin 3 receptor, and relaxin/insulin-like family peptide receptor 1 (RXFP1) mRNA were expressed 280, 185, 202, 183, and 163% greater, respectively (P < 0.01), while proopiomelanocortin (POMC) mRNA was expressed 42% lower in LRFI than HRFI animals (P < 0.05). Hypothalamic GnRH mRNA expression was 67% lower while gonadotropin inhibiting hormone (GnIH) mRNA was 209% higher in LRFI than HRFI animals (P < 0.01). Pituitary expression of FSHβ and LHβ correlated to hypothalamic GnRH levels (P < 0.05) indicating changes in gene expression within the hypothalamus had functional consequences. Leptin mRNA expression levels were not different between adipose tissue of LRFI or HRFI steers (P < 0.84). These data indicate that animals with superior RFI evaluated during warm conditions have higher expression of orexigenic neuropeptide genes independent of the expression of adipose-derived leptin. Furthermore, the gonadotropin axis may also influence feed efficiency under these conditions.

Duodenal–Jejunal Bypass Improves Glucose Metabolism and Adipokine Expression Independently of Weight Loss in a Diabetic Rat Model

There is accumulating evidence that adipokines lead to a proinflammatory state, which plays crucial roles in insulin resistance and development of type 2 diabetes mellitus (T2DM). Previous studies demonstrated that weight loss after bariatric surgery is accompanied by a suppression of the proinflammatory state. However, the effect of bariatric surgery on adipokine expression beyond weight loss is still elusive. The aim of this study was to investigate the effect of duodenal-jejunal bypass (DJB) on glucose homeostasis and adipokine expression independently of weight loss. A T2DM rat model was developed by a high-fat diet and low dose of streptozotocin. Twenty-one diabetic rats and 10 age-matched SD rats were randomly assigned to the DJB group, sham-DJB (S-DJB) group, and control group. For 12weeks after surgery, their body weight, food intake, glucose homeostasis, lipid parameters, serum adipokine levels, and adipokine gene expression in the mesocolon adipose tissue were measured. Compared to the S-DJB group, DJB induced significant and sustained glycemic control with improved insulin sensitivity and glucose tolerance independently of weight loss. DJB improved the lipid metabolism by decreasing fasting free fatty acids and triglycerides. Serum leptin and IL-6 significantly decreased 12weeks after DJB, whereas adiponectin increased and TNF-α remained unchanged. The mRNA expression levels of leptin, TNF-α, and IL-6 decreased, whereas adiponectin increased in the mesocolon adipose tissue. DJB reduced the proinflammatory adipokines and increased the anti-inflammatory adipokines independently of weight loss, which may contribute to the improvement of insulin sensitivity.

Serum leptin concentrations, leptin mRNA expression, and food intake during the estrous cycle in rats

The aim of this study was to investigate food intake, serum leptin levels, and leptin mRNA expression during the sexual cycle in rats. Female Wistar-Imamichi rats aged 8-10 weeks were used in this experiment. Food intake was measured during the light and dark phases (light on at 07:00 and off at 19:00) of the 4-day estrous cycle in female rats. Serum leptin levels were measured by ELISA, and leptin mRNA expression levels were analyzed using real-time PCR on diestrous- and proestrous-stage rats. Our results revealed that during the sexual cycle, food intake was significantly higher in the dark phase compared with the light phase. Food intake in proestrous females was significantly lower in the light and dark phases compared with the other groups. Serum leptin concentrations were significantly higher in both phases in proestrous rats compared with diestrous rats. There was a significant increase in leptin mRNA expression in adipose tissue during the proestrous period compared with the diestrous period. These findings suggest that increased leptin mRNA expression and serum leptin levels, which are induced by estrogen during the proestrous stage, may play a role in regulating appetitive behavior.

Abstract P6-05-11: Leptin and Leptin receptor expression in human breast cancer

Abstract INTRODUCTION: Leptin is a protein that plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism. It is one of the most important adipose derived hormones and has been suggested to act as a growth factor in neoplasms. Obesity has been linked to increased risk of breast cancer in postmenopausal women. Increased peripheral production of oestrogen has been regarded as the main cause for this association, but other factors affecting fat metabolism may be implicated. There is recent evidence that Leptin stimulates cancer cell proliferation in MCF-7 cancer cells. Both Cox2 and hTERT have been proposed as mediators of Leptin's carcinogenic role. Our objective was to determine, using quantitative PCR, whether the mRNA expression levels of Leptin and Leptin receptor were consistent with a tumour proliferative function and whether levels from these genes were positively correlated with clinical outcome in breast cancer. METHODS: A total of 153 samples were analysed. The levels of transcription of Leptin and its receptor were determined using quantitative PCR and normalised against (CK19). Transcript levels within breast cancer specimens were compared to normal background tissues and analysed against conventional pathological parameters and clinical outcome over a 10 year follow-up period. RESULTS: The levels of Leptin and Leptin receptor mRNA were significantly higher in malignant samples (p = 0.0011 and 0.0014 respectively). This difference remained statistically significant when comparing levels between normal samples and all malignant subgroups according to their NPI, grade, stage, local recurrence, and distant metastasis in both ER receptor positive and negative samples. It was also present across all histological types for both Leptin and its receptor. There was no significant change in mRNA transcription levels correlating with tumour grade, stage, disease free survival, or development of loco regional recurrence. There was also no statistically significant difference in levels of expression of both Leptin and its receptor when comparing ER positive to negative patients (p = 0.74 and 0.27 respectively). Leptin levels showed a significantly positive correlation with Leptin receptors (r = 0.504, 0.0000000222). We have observed no significant correlations between Leptin and hTERT or Cox2. CONCLUSION: This study demonstrates compelling evidence that both Leptin and Leptin receptor mRNA transcription levels are more readily expressed in cancerous tissues providing further evidence that it plays a significant role in the process of breast carcinogenesis. However, Leptin levels did nor correlate with tumor's stage, clinical outcome, hTERT or Cox-2 levels. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-05-11.