Expression Of Obesity-related Genes Research Articles

Efficacy of Probiotic Strains Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093 in Management of Obesity: An In Vitro and In Vivo Analysis.

The prevalence of obesity, characterized by an excessive accumulation of adipose tissue and adipocyte hypertrophy, presents a major public health challenge. This study investigates the therapeutic potential of two probiotic strains, Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093, in the context of obesity. Utilizing 3T3-L1 cell-derived human adipocytes, we assessed Probio65's and Probio-093's capacity to mitigate triglyceride accumulation and influence adipocytokine production in vitro. Subsequently, an in vivo trial with male C57BL/6J mice examined the effects of both probiotic strains on adipose tissue characteristics, body weight, fat mass, and obesity-related gene expression. This study employed both live and ethanol-extracted bacterial cells. The results demonstrated significant reductions in the triglyceride deposition, body weight, and adipose tissue mass in the treated groups (p < 0.05). Furthermore, both strains modulated adipokine profiles by downregulating proinflammatory markers such as PAI-1, leptin, TNF-α, STAMP2, F4/80, resistin, and MCP-1, and upregulating the insulin-sensitive transporter GLUT4 and the anti-inflammatory adiponectin (p < 0.05). Our findings suggest that Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093 are promising agents for microbiome-targeted anti-obesity therapies, offering the effective mitigation of obesity and improvement in adipocyte function in a murine model.

Anti-obesity activity of lactic acid bacteria-starter-based kimchi in high-fat diet-induced obese mice

Previously, lactic acid bacteria (LAB) and selected LAB-inoculated kimchi (SK) have anti-obesity activity in vitro. Herein, anti-obesity activity of SK was investigated in vivo. LAB-uninoculated kimchi (NK) and SK were orally administered (70 mg/kg) for 8 weeks to high-fat diet (HFD)-fed mice. The body weight, food efficiency rate (FER), and body composition were measured. Serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), adipocytokine, and lipid profiles and lipid accumulation levels were assessed. The effects of SK on microbiome changes were investigated. In kimchi groups, body weight, body fat, and organ weight and lipid profiles in low GOT and GPT levels significantly decreased (p < 0.05); serum adiponectin and leptin levels increased and decreased, respectively. Kimchi significantly decreased obesity-related gene expression and lipid accumulation (p < 0.05). Kimchi corrected HFD-induced gut microbiome imbalance, notably with more reliable recovery in the SK group. Its in vivo confirmed anti-obesity activity supports using kimchi's health functionalities.

Anti-obesity effects of kimchi with red yeast rice in 3T3-L1 adipocytes and high-fat diet-induced obese mice

Red yeast rice is fermented rice with Monascus purpureus and contains monacolin K, which decreases cholesterol levels. Here, the anti-obesity effect of kimchi with red yeast rice (RYRK) was investigated in vitro and in vivo. Initially, the anti-obesity effect of RYRK was examined by measuring triglyceride (TG) content and obesity-related gene expression in 3T3-L1 adipocytes. RYRK (100 mg/kg) were then orally administered for 8 weeks with a high-fat diet. Body weight and serum GOT and GPT were measured. The inhibitory effect of RYRK on lipid profiles and accumulation was assessed. RYRK significantly reduced TG content and obesity-related gene expression with low cytotoxicity (p < 0.05). RYRK significantly reduced body weight and serum and hepatic lipid profiles without hepatic damage (p < 0.05). RYRK inhibited lipid accumulation in H&E and ORO results. Overall, the anti-obesity effect of RYRK was established, resulting in a better understanding of the health benefits of kimchi.

High-fat diet causes transgenerational alteration in the expression of Obesity-related genes in mouse seminal vesicles

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Obesity-induced changes in gene expression in feline adipose and skeletal muscle tissue.

Indoor-confined cats are prone to developing obesity due to a sedentary life and an energy intake exceeding energy requirements. As in humans, feline obesity decreases insulin sensitivity and increases the risk of developing feline diabetes mellitus, but the pathophysiological mechanisms are currently poorly understood. Human obesity-related metabolic alterations seem to relate to changes in the expression of genes involved in glucose metabolism, insulin action and inflammation. The objective of the current study was to investigate changes in the expression of genes relating to obesity, glucose metabolism and inflammation in cats with non-experimentally induced obesity. Biopsies from the sartorius muscle and subcutaneous adipose tissue were obtained from 73 healthy, neutered, indoor-confined domestic shorthaired cats ranging from lean to obese. Quantification of obesity-related gene expression levels relative to glyceraldehyde-3-phosphate dehydrogenasewas performed by quantitative real-time polymerase chain reaction. A negative association between obesity and adiponectin expression was observed in the adipose tissue (mean ± SD; normal weight, 27.30 × 10-3 ± 77.14 × 10-3 ; overweight, 2.89 × 10-3 ± 0.38 × 10-3 and obese, 2.93 × 10-3 ± 4.20 × 10-3 , p < 0.05). In muscle, the expression of peroxisome proliferative activated receptor-γ2and plasminogen activator inhibitor-1was increased in the obese compared to the normal-weight cats, and resistin was increased in the normal-weight compared to the overweight cats. There were no detectable obesity-related changes in the messenger RNA levels of inflammatory cytokines. In conclusion, a possible obesity-related low-grade inflammation caused by increased expression of key proinflammatory regulators was not observed. This could imply that the development of feline obesity and ensuing insulin resistance may not be based on tissue-derived inflammation, but caused by several determining factors, many of which still need further investigation.

Obesity alters the mouse endometrial transcriptome in a cell context-dependent manner

Obesity impacts fertility and is positively correlated with endometrial hyperplasia and endometrial cancer occurrence. Endometrial epithelia often harbor disease driver-mutations, while endometrial stroma are highly regulative of neighboring epithelia. Here, we sought to determine distinct transcriptome changes occurring in individual cell types in the obese mouse uterus. Outbred CD-1 mice were fed high-fat or control diets for 18 weeks, estrous cycle staged, and endometrial epithelia, macrophages, and stroma isolated for transcriptomic analysis. High-fat diet mice displayed increased body mass and developed glucose intolerance, hyperinsulinemia, and fatty liver. Obese mouse epithelia displayed differential gene expression for genes related to innate immunity and leukocyte chemotaxis. The obese mouse stroma differentially expressed factors related to circadian rhythm, and expression of these genes correlated with glucose tolerance or body mass. We observed correlations between F4/80 + macrophage numbers, Cleaved Caspase 3 (CC3) apoptosis marker staining and glucose intolerance among obese mice, including a subgroup of obese mice with high CC3 + luminal epithelia. This subgroup displayed differential gene expression among all cell types, with pathways related to immune escape in epithelia and macrophages, while the stroma dysregulated pathways related to regulation of epithelia. These results suggest an important role for differential response of both the epithelia and stroma in their response to obesity, while macrophages are dysregulated in the context of apoptotic epithelia. The obesity-related gene expression programs in cells within the uterine microenvironment may influence the ability of the endometrium to function during pregnancy and influence disease pathogenesis.

Obesity-Related Genes Expression in Testes and Sperm Parameters Respond to GLP-1 and Caloric Restriction.

Aim: Calorie restriction (CR) diets and glucagon-Like Peptide-1 (GLP-1) analogs are known to alter energy homeostasis with the potential to affect the expression of obesity-related genes (ORGs). We hypothesized that CR and GLP-1 administration can alter ORGs expression in spermatozoa and testes, as well as the sperm parameters implicated in male fertility. Materials and Methods: Six-week-old adult male Wistar rats (n = 16) were divided into three groups, submitted either to CR (n = 6, fed with 30% less chow diet than the control rats), GLP-1 administration (n = 5, 3.5 pmol/min/kg intraperitoneal) for 28 days, or used as controls (n = 5, fed ad libitum). Selected ORGs expression, namely the fat mass and obesity-associated (FTO), melanocortin-4 receptor (MC4R), glucosamine-6-phosphate deaminase 2 (GNPDA2), and transmembrane protein 18 (TMEM18) were evaluated in testes and spermatozoa by a quantitative polymerase chain reaction (qPCR). Results: CR resulted in lower body weight gain and insulin resistance, but a higher percentage of sperm head defects. GLP-1 administration, despite showing no influence on body weight or glucose homeostasis, resulted in a lower percentage of sperm head defects. CR and GLP-1 administration were associated with a higher expression of all ORGs in the testes. Under CR conditions, the genes FTO and TMEM18 expression in the testes and the MC4R and TMEM18 transcripts abundance in sperm were positively correlated with the spermatozoa oxidative status. The abundance of FTO and TMEM18 in the spermatozoa of rats under CR were positively correlated with sperm concentration, while the testes’ TMEM18 expression was also positively correlated with sperm vitality and negatively correlated with insulin resistance. Testes GNPDA2 expression was negatively correlated with sperm head defects. Conclusions: CR and GLP-1 administration results in higher ORGs expression in testes, and these were correlated with several alterations in sperm fertility parameters.

The Impact of Harsh Parenting on the Development of Obesity in Adulthood: An Examination of Epigenetic/Gene Expression Mediators Among African American Youth.

Objective: We examined the association of prospectively assessed harsh parenting during adolescence with body mass index (BMI) in young adulthood among African American youth. We also assessed the role of methylation of obesity-related genes and gene expression markers of obesity as mediators of this association, providing a pathway for the biological embedding of early harsh parenting and its long-term impact on young adult health.Methods: Hypotheses were tested with a sample of 362 African American youth for whom harsh parenting was assessed at ages 10–15, BMI was assessed at age 10 and 29, and both DNA methylation (DNAm) and gene expression of obesity genes were assessed at age 29. Mediational analyses were conducted using bootstrap methods to generate confidence intervals.Results: Controlling for genetic risk for obesity and health-related covariates, harsh parenting across childhood and adolescence was associated with change in BMI (Δ BMI) from ages 10–29. In addition, we found that the indirect effect of harsh parenting on Δ BMI was mediated through obesity-related DNAm and accounted for 45.3% of the total effect. Further, obesity-related DNAm mediated the effect of harsh parenting on gene expression of obesity-related genes (GEOG), and GEOG, in turn, mediated the impact of obesity-related DNAm on ΔBMI. This pathway accounted for 3.4% of the total effect. There were no gender differences in the magnitude of this indirect effect.Conclusions: The results suggest that alterations in methylation and gene expression mediate the impact of harsh parenting on change in obesity from childhood to young adulthood, illustrating plausible biological pathways from harsh parenting to obesity and bolstering the hypothesis that harsh parenting in childhood and adolescence can become biologically embedded and contribute to obesity.

Associations between obesity-related gene expression in maternal and cord blood and newborn adiposity: findings from the Araraquara Cohort study.

Genes involved in the regulation of metabolism, adipose tissue deposition, inflammation, and the appetite-satiety axis may play an important role in fetal development, and possibly induce permanent metabolic changes and fat accumulation. In this study we investigated: (1) obesity-related gene expression in maternal and cord blood of overweight/obese and normal-weight pregnant women; (2) associations between obesity-related gene expression in maternal and cord blood; and (3) associations of gene expression in each of maternal and cord blood with newborn adiposity. Twenty-five overweight/obese and 32 normal-weight pregnant women were selected from the Araraquara Cohort Study according to their pre-pregnancy BMI. Maternal and cord blood gene expression of LEPR, STAT3, PPARG, TLR4, IL-6, IL-10, FTO, MC4R, TNF-α, and NFκB were investigated by relative real-time PCR quantification. The body composition of the newborns was assessed by air displacement plethysmography. Associations between maternal and cord blood gene expression and markers of newborn adiposity (weight, BMI, and fat mass%) were explored by linear regression models controlling for maternal age, pre-pregnancy BMI, maternal gestational weight gain, gestational age, and newborn sex. There was higher TLR4, NFκB, and TNF-a expression, and lower IL-6 expression, in overweight/obese pregnant women and their respective newborns compared with normal-weight women and their newborns (p < 0.001). Maternal PPARG gene expression was associated with both weight and fat mass % of the newborns, and cord blood IL-10 expression was associated with BMI and fat mass %, controlling for confounders. To our knowledge, this is the first study to evaluate the relationship of maternal and cord blood gene expression with adiposity markers of the newborn. Our results provide evidence for the contribution of maternal and cord blood gene expression-particularly maternal PPARG and TLR4 expression, and cord blood IL-10 expression-to newborn weight, BMI, and fat mass %.

Expression of obesity-related genes in human spermatozoa affects the outcomes of reproductive treatments

To study the abundance of obesity-related gene (ORG) mRNA in human spermatozoa and its association with sperm quality parameters, embryonic development, and pregnancy rates after assisted reproduction treatment (ART). Cross-sectional study of spermatozoa ORG mRNA expression, and sperm and embryonic development parameters of infertile couples attending a single ART center. University, in collaboration with a medically assisted reproduction center. One hundred six couples seeking fertility treatment and receiving ART. Expression of spermatozoa ORG mRNA was assessed by quantitative reverse transcription-polymerase chain reaction. Sperm and embryonic development parameters were measured by board-certified embryologists. Serum β-human chorionic gonadotropin levels and fetal heartbeat detection on ultrasound were used to document biochemical and clinical pregnancy, respectively. Correlations between the abundance of ORG transcripts in spermatozoa and sperm quality, embryonic development, and achievement of pregnancy. The abundance of spermatozoa FTO mRNA was positively correlated with total sperm count (r = 0.5030), fertilization rate (r = 0.4854), embryo cleavage rate (r = 0.5705), and high-quality embryo rate (r = 0.6982). The abundance of spermatozoa MC4R transcript was negatively correlated with sperm viability (r = -0.3111) and positively correlated with biochemical pregnancy (r = 0.4420). The abundance of MC4R and GNPDA2 transcripts was higher in spermatozoa of men with asthenozoospermia and teratozoospermia than in those with normozoospermia. To our knowledge, this is the first report showing that the abundance of MC4R and FTO transcripts in spermatozoa is associated with sperm and embryo quality parameters, as well as pregnancy rates. Overall, these results further support the view that male factors beyond classic sperm quality parameters, namely the abundance of ORG transcripts, also affect the outcome of ART.

Anti-obesity effect of Yangkyuksanwha-tang in high-fat diet-induced obese mice

BackgroundYangkyuksanwha-tang (YST) is an herbal medicine based on Sasang constitutional medicine (SCM) and is widely used in Korean traditional medicine. The aim of the study was to evaluate the effect of YST on obesity in high-fat diet (HFD)-induced obese mice.MethodsWe induced obesity in C57bl/6 J mice using a HFD, and then orally administered 300 mg/kg YST for 6 weeks. We measured body weight, food efficiency, organ and fat weight, serum biochemical parameters, and obesity-related gene expression, and carried out histological analysis at the end of the experimental period.ResultsYST significantly reduced the absolute body weight and food efficiency ratio. The serum, aminotransferase, glucose, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels were significantly lower in the YST-treated group than in the control group, whereas the high-density lipoprotein-cholesterol level in the YST-treated group was significantly higher. The YST-treated group also showed a significant reduction in regional fatty tissues and the absolute weight of various organs. We also observed a significantly reduced expression of AP2/FABP4, C/EBP-β, leptin, and SREBP1c/ADD1 mRNA, and significantly increased expression of UCP-2 and adiponectin mRNA in adipose tissue in the YST-treated group. YST also decreased the lipid droplet size and lipid accumulation in the liver, as well as adipocyte size in epididymal adipose tissue. At the dose tested, YST was non-toxic to the liver and kidneys of the mice.ConclusionThe results imply that YST has anti-obesity effects in obesity-induced mice. Although the number of experimental animals was limited and the drug effects concern mice, rather than humans, which have different constitutions, the study has valuable implications with respect to the general effects of YST.

Vertical Sleeve Gastrectomy Attenuates Hedonic Feeding Without Impacting Alcohol Drinking in Rats.

Objective:Roux-en-Y gastric bypass (RYGB) surgery and Vertical Sleeve Gastrectomy (VSG) are most commonly performed bariatric procedures. While studies report new onset alcohol misuse following RYGB, the impact of VSG on alcohol intake is less clear. We evaluated hedonic feeding, alcohol drinking and hypothalamic obesity-related gene expression following VSG.Methods:Male Long Evans rats underwent VSG or sham surgery. To evaluate hedonic feeding, rats received a high-fat diet following behavioral satiation on chow. Alcohol (5-10% v/v) drinking was assessed in a two-bottle choice paradigm. Finally, PCR array evaluated gene expression.Results:VSG induced a moderate but significant weight loss. Sham rats significantly escalated high-fat diet intake following behavioral satiation, an effect significantly reduced in VSG rats. A moderate decrease in alcohol intake was observed in VSG rats at low (5%) alcohol concentration. However, overall no significant between group differences were evident. Key hypothalamic orexigenic transcripts linked to stimulation of food and alcohol intake were significantly decreased in VSG rats.Conclusions:VSG attenuated hedonic feeding without impacting alcohol drinking, an effect potentially mediated by alterations in genetic information flow within the hypothalamus. Importantly, these data highlight VSG as an effective bariatric procedure with potentially reduced risk of developing alcohol use disorder.

Abstract 3999: MicroRNA expression links obesity and recurrence in renal cell carcinoma

Abstract Obesity is an established risk factor for clear cell renal cell carcinoma (ccRCC) development and prognosis; however, the mechanisms underlying this link remain unclear. In the present study, we set to assess whether microRNAs (miRNAs) can serve as a molecular link between obesity and recurrence in ccRCC. Through bioinformatics tools and literature search, we identified 126 obesity-related miRNAs. Supplemented with 25 miRNAs which were differentially expressed between ccRCC from normal kidney, we tested the association of these miRNAs with ccRCC recurrence. Significantly decreased levels of hsa-miR-204-5p were found in recurrent ccRCC patients with an over 2-fold increased risk of recurrence (HR = 2.15, p = 0.028, MST = 25.6 vs. 47.2 months). Correlations between miRNA expression and the predicted target genes were tested using gene profiling data generated from these same patients. We found strong inverse correlations between miR-204 expression and several obesity-related genes, including IGF2BP2 (r = -0.40, p = 4.14×10−4), a member of the insulin growth receptor signaling pathway. This correlation was further validated in TCGA data (r = -0.58, p = 1.40×10−22). We also found that low level of hsa-miR-139-5p was significantly associated with increased recurrence risk (HR = 2.37, p = 0.026, MST = 32.2 vs. 51.3 months). In conclusion, we found a set of obesity-related miRNAs that are dysregulated in ccRCC tissues, and some of these miRNAs, such as hsa-miR-204-5p, were associated with the recurrence of RCC, potentially through regulating obesity-related gene expression. Citation Format: Xiang Shu, Michelle A. Hildebrandt, Jian Gu, Nizar M. Tannir, Surena Matin, Jose A. Karam. MicroRNA expression links obesity and recurrence in renal cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3999. doi:10.1158/1538-7445.AM2015-3999

Peptide derived from desalinated boiled tuna extract inhibits adipogenesis through the downregulation of C/EBP-α and PPAR-γ in 3T3-L1 adipocytes.

Recently, obesity has increased due to a variety of reasons, including the availability of 'fast food' and high-fat diets. Developing anti-obesity functional drugs and foods from natural sources may offer solutions to this global concern. Generally, tuna is a high-protein, low-fat and low-calorie food with various bioactive effects. It may improve memory, reduce cholesterol levels and positively affect the development of brain cells. In this study, we screened the anti-obesity potential of peptides derived from tuna protein. We then observed protein bands by the Coomassie blue staining of a sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel. The protein mixture was concentrated and desalted using in-gel trypsin digestion and a C18 nano column and Poros R2 reversed-phase preparation, prior to quadrupole time-of-flight mass spectrometry (Q-TOF MS/MS). We screened the peptides for their ability to affect adipogenesis in 3T3-L1 adipocytes. We also measured glucose uptake, triglyceride levels and lipid droplets using Oil Red O staining. As a result, we confirmed that one peptide inhibited adipocyte differentiation. We also observed the expression of obesity-related genes by western blot analysis and reverse transcription-polymerase chain reaction. The peptide from the tuna extract significantly reduced the expression levels of CCAAT/enhancer-binding protein α (C/EBP-α) and peroxisome proliferator-activated receptor-γ (PPAR-γ) adipocyte marker genes. Thus, our data suggest that this peptide from boiled tuna extract reduces lipid components and adipogenesis in 3T3-L1 cells, and these characteristics may be of value in the development of anti-obesity foods.

DNA methylation differences in CD16+ cells between normal weight and obese women of childbearing age (1120.11)

It is well established that DNA cytosine methylation epialleles (CG vs 5MeCG) alter the expression of obesity related genes. The current study examined differences in 5MeCG in CD16+ cells isolated from blood using antibody‐bound magnetic beads in normal weight (BMI 18.5‐24.9 kg/m2; n = 12) and obese (BMI &gt; 30 kg/m2; n = 6) women (18‐35y). 5MeCG was measured across &gt; 485,000 CG sites using the HumanMethylation450 BeadChip (Illumina©). 16,969 CG sites were differentially methylated in obese as compared to normal weight women (p &lt; 0.05). 65.4% of these sites had decreased methylation. Six of these CG’s remained associated (p &lt; 10‐7) after adjustment for multiple testing (False Discovery Rate &lt; 0.05), including sites in CRYGB, CDH5, and VASH1. Our results have potential implications in obesity and CDH5 has been shown previously to have differential methylation in peripheral blood leukocytes in obese (Wang et al. doi: 10.1186/1741‐7015‐8‐87). Continued analysis will further examine these methylation differences.Grant Funding Source: Supported by a grant from the UGA Obesity Initiative and the GRA Eminent Scholar Endowment (CAB)

BICHEMICAL ALTERATIONS INDUCED BY AMYLIN IN WISTAR RATS

Amylin is a peptide hormone synthesized in β cells of pancreas together with insulin in response to glucose and nutrients. Amylin controls food intake and body weight but the exact mechanism is still unknown. This study aimed to examine the effects of amylin injection on hormones, metabolites and cytokines expression in rats. Wistar rats were injected amylin Intraperitoneally (IP) (10 µg kg-1 twice daily) for 7 days. Plasma and liver samples were collected for blood measurements and RT-PCR analysis. Amylin treatments induced significant decrease in body weight and food intake in time dependent manner. Moreover, amylin significantly increased insulin, leptin and lipase secretion. A decrease in plasma triglycerides, cholesterol and LPL and increase in HDL levels was recorded. There are upregulation in the expression of IL-1β and TNF-α in amylin treated rats. The results collectively indicate that amylin has anti-obesity like effects through regulation of proteins and obesity related gene expression.

1043 – Expression of obesity related genes and leptin serum levels are decreased in turkish schizophrenia patients, case-control study

Antipsychotic medications can induce metabolic abnormalities (weight gain) in schizophrenia (SCH). Leptin receptor (LEPR), leptin (LEP) and peroxysome proliferator-activated receptor g2 (PPARg2) are the potential genetic determinants which might be liable of the metabolic dysregulation. The aim of this study was to evaluate the effect of LEP c.-2548G>A, LEPR p.Q223R polymorphisms and the impact of mRNA levels of LEP, LEPR, and PPARg2 along with the serum leptin levels on metabolic adversities in SCH patients (n=132) and controls (n=114). Metabolic profiles, LEP, LEPR gene polymorphisms and the gene expressions of LEP, LEPR and PPARg2 were studied in SCH patients and controls. BMI, cholesterol and fasting glucose levels were higher in SCH patients compared to controls. LEP c.-2548 (GA+AA) genotypes were two fold lower in SCH patients versus controls (p< 0.05), and no significant difference was observed in LEPR p.Q223R genotypes. Interestingly, leptin serum levels were lower in SCH patients compared to controls (p< 0.05). Leptin, leptin receptor and PPARg2 gene expressions were found to be decreased in SCH patients compared to controls (p< 0.001, p< 0.001 and p≤0.05, respectively). Leptin receptor, leptin and PPARg2 genes could be potential risk factors in developing metabolic adversities in SCH.

Effect of Peucedanum japonicum Thunb Extract on High-fat Diet-induced Obesity and Gene Expression in Mice

Supplementation of the diet with Peucedanum japonicum Thunb (PJT) powder inhibits high-fat diet-induced obesity in mice. Either the fiber component or other bioactive components in the PJT powder may inhibit obesity. This study, therefore, was an attempt to identify the components, fiber or other phytochemicals of PJT that were responsible for the anti-obesity activity, and also studied the modulation of obesity-related gene expression in C57BL/6 mice. Animals were fed a modified-AIN76 diet supplemented with PJT powder or extracts of PJT in water, 50 % ethanol, or ethanol. Body weight gain, tissue weight, serum biochemical parameters, liver lipid concentrations, and gene expression in tissues were compared between the control and treatment groups. Of the extracts, the ethanol extract of PJT decreased fat accumulation and adipocyte size, reduced serum and liver triglyceride concentrations, and inhibited obesity. This finding clearly demonstrates the presence of anti-obesity phytochemicals in PJT. Ethanol extract of PJT inhibited lipase activity in vitro. Modulation of gene expression by PJT ethanol extract was largely similar to that by PJT powder in the hepatic and adipose tissues: RORC and PBEF1 were upregulated and DUSP1, INSIG2, and SERPINA12 were downregulated in the liver; FXRα and PPARγ were upregulated and PEG1/MEST, the size-marker of adipocytes, was downregulated in the adipose tissue. Furthermore, PJT ethanol extract increased the expression of the UCP3 gene in muscle. These results suggest that the anti-obesity phytochemicals in PJT lower lipid levels by inhibiting fat absorption and by modulating obesity-related gene expression in the liver, adipose tissue, and muscle.

Effect of Peucedanum japonicum Thunb on the Expression of Obesity-Related Genes in Mice on a High-Fat Diet

The present study describes the effect of Peucedanum japonicum Thunb (PJT) intake on the expression of obesity-related genes in mice fed a high-fat diet. To explore the mechanism underlying the effect of PJT, This study focused on the expression of genes, especially those related to obesity and metabolism syndrome, in the liver and adipose tissues. In agreement with our previous observations, intake of 10 % PJT for 4 weeks significantly reduced serum triglyceride (TG), leptin, abdominal fat, and adipocyte size. PJT also significantly increased fecal excretion of TG, decreased that of bile acid, and tended to increase the fecal excretion of total cholesterol. Microarray analysis was used to monitor changes in 324 metabolic syndrome-related genes in the liver. Statistically significant upregulation of PPP1R10, RORC, and PBEF1 genes and downregulation of DUSP1, INSIG2, and SERPINA12 genes were noted and confirmed by real-time RT-PCR. These changes were indicative of increased fatty acid oxidation in the maintenance of lipid homeostasis and insulin sensitivity in the livers of PJT-fed mice. PJT increased the expression of PPARγ, FXRα, DGAT1, and ATGL genes, suggesting an enhancement of adipocyte differentiation and normalization of functionality of adipose tissue.

Weight gain, schizophrenia and antipsychotics: new findings from animal model and pharmacogenomic studies.

Excess body weight is one of the most common physical health problems among patients with schizophrenia that increases the risk for many medical problems, including type 2 diabetes mellitus, coronary heart disease, osteoarthritis, and hypertension, and accounts in part for 20% shorter life expectancy than in general population. Among patients with severe mental illness, obesity can be attributed to an unhealthy lifestyle, personal genetic profile, as well as the effects of psychotropic medications, above all antipsychotic drugs. Novel “atypical” antipsychotic drugs represent a substantial improvement on older “typical” drugs. However, clinical experience has shown that some, but not all, of these drugs can induce substantial weight gain. Animal models of antipsychotic-related weight gain and animal transgenic models of knockout or overexpressed genes of antipsychotic receptors have been largely evaluated by scientific community for changes in obesity-related gene expression or phenotypes. Moreover, pharmacogenomic approaches have allowed to detect more than 300 possible candidate genes for antipsychotics-induced body weight gain. In this paper, we summarize current thinking on: (1) the role of polymorphisms in several candidate genes, (2) the possible roles of various neurotransmitters and neuropeptides in this adverse drug reaction, and (3) the state of development of animal models in this matter. We also outline major areas for future research.