scholarly journals Effects of maternal consumption of morphine on rat skeletal system development

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Maryam Saeidinezhad ◽  
Vahid Razban ◽  
Hosein Safizadeh ◽  
Massood Ezzatabadipour
Keyword(s):  
Gene Expression ◽  
Alkaline Phosphatase ◽  
Growth Plate ◽  
System Development ◽  
Cell Number ◽  
Female Rats ◽  
Male Rats ◽  
Skeletal System ◽  
Maternal Consumption ◽  
Sox9 Gene

Abstract Background Opioid abuse is among the most ubiquitous issues world-wide, and when it happens in mothers, it puts them at risk of diseases that can be transferred to the next generation. Previous studies have indicated that morphine addiction during pregnancy could inhibit development in rat embryos and infants. The present study focused on the effects of maternal consumption of morphine on rat skeletal system development and also investigate the molecular pathway of chondrogenesis and osteogenesis of infants from control and addicted rat groups. Methods Thirty-two female rats were randomly assigned to four groups. The groups consisted of one- and seven-day-old female infants which were born of morphine-dependent mothers and a control group for each of them. Experimental groups received oral morphine at the final dose of 0.4 mg/ml/day. Withdrawal signs were confirmation of morphine dependency. Female rats were crossed with male rats and coupling time was recorded. Fixed bones of all groups were processed and then stained by hematoxyline-eosin method. Thickness and cell number of proximal and distal growth plate of bones were measured. The cartilage and bone cells were stained by alcian blue/alizarin red method. Additionally, the gene expression of alkaline phosphatase, osteocalcin, and COLL2 and SOX9 gene expression were studied immuno-histochemically. Results Unfavorable effects of morphine on histological measurements were observed in one-day and seven-day infants, with more effects on seven-day infants. The thickness and cell number of the proximal and distal growth plate of morphine-dependent rat offsprings were reduced significantly. Furthermore, morphine reduced growth of primary and secondary ossification centers, and thus, longitudinal bone growth was reduced. Moreover, a decrease in the alkaline phosphatase, osteocalcin, COLL2 and SOX9 gene expression, and the number of stained cells was observed. More adverse effects of morphine in seven-day infants compared to one-day infants which showed the time dependent of morphine to the time length of administration. Conclusion Histochemistry and immunohistochemistry findings on cartilage and bone matrix formation, as well as protein expression of chondrogenic and osteogenic markers suggest that morphine dependence in pregnant mothers may impair intra-cartilaginous osteogenesis in post-natal rats.

scholarly journals Sex-Dependent Changes in Right Ventricular Gene Expression in Response to Pressure Overload in a Rat Model of Pulmonary Trunk Banding

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 430
Author(s):  
Hicham Labazi ◽  
Julie Birkmose Axelsen ◽  
Dianne Hillyard ◽  
Margaret Nilsen ◽  
Asger Andersen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Right Ventricular ◽  
Pressure Overload ◽  
Pulmonary Trunk ◽  
Female Rats ◽  
Male Rats ◽  
Type I ◽  
Male And Female ◽  
Collagen Iii ◽  
Rv Function

Right ventricular hypertrophy (RVH) and subsequent failure are consequences of pulmonary arterial hypertension (PAH). While females are four times more likely to develop PAH, male patients have poorer survival even with treatment, suggesting a sex-dependent dimorphism in right ventricular (RV) hypertrophy/compensation. This may result from differential gene expression in the RV in male vs. female. To date, the sex dependent effect of pressure overload on RV function and changes in gene expression is still unclear. We hypothesize that pressure overload promotes gene expression changes in the RV that may contribute to a poorer outcome in males vs. females. To test this hypothesis, male and female Wistar rats underwent either a sham procedure (sham controls) or moderate pulmonary trunk banding (PTB) (a model of pressure overload induced compensated RV hypertrophy) surgery. Seven weeks post-surgery, RV function was assessed in vivo, and tissue samples were collected for gene expression using qPCR. Compared to sham controls, PTB induced significant increases in the right ventricular systolic pressure, the filling pressure and contractility, which were similar between male and female rats. PTB resulted in an increase in RVH indexes (RV weight, RV weight/tibia length and Fulton index) in both male and female groups. However, RVH indexes were significantly higher in male-PTB when compared to female-PTB rats. Whilst end of procedure body weight was greater in male rats, end of procedure pulmonary artery (PA) diameters were the same in both males and females. RV gene expression analysis revealed that the following genes were increased in PTB-male rats compared with the sham-operated controls: natriuretic peptide A (ANP) and B (BNP), as well as the markers of fibrosis; collagen type I and III. In females, only BNP was significantly increased in the RV when compared to the sham-operated female rats. Furthermore, ANP, BNP and collagen III were significantly higher in the RV from PTB-males when compared to RV from PTB-female rats. Our data suggest that pressure overload-mediated changes in gene expression in the RV from male rats may worsen RVH and increase the susceptibility of males to a poorer outcome when compared to females.

scholarly journals Effects of Diet-Induced Obesity on Hypothalamic Kisspeptin-Neurokinin-Dynorphin (KNDy) Neurons and Luteinizing Hormone Secretion in Sex Hormone-Primed Male and Female Rats

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A537-A537
Author(s):  
Shiori Minabe ◽  
Kinuyo Iwata ◽  
Hitoshi Ozawa
Keyword(s):  
Gene Expression ◽  
Luteinizing Hormone ◽  
High Fat Diet ◽  
Female Rats ◽  
Male Rats ◽  
High Fat ◽  
Neurokinin B ◽  
Male And Female ◽  
Male And Female Rats ◽  
Kndy Neurons

Abstract Metabolic stress resulting from a nutrient excess causes infertility in both sexes. Kisspeptin-neurokinin B-dynorphin (KNDy) neurons in the arcuate nucleus (ARC) have been suggested to be key players in reproduction via direct stimulation of gonadotropin-releasing hormone (GnRH) and subsequent gonadotropin release in mammalian species. In this study, we investigated the sex differences in the effects of a high-fat diet (HFD) on KNDy-associated gene expression in the ARC to determine the pathogenic mechanism underlying obesity-induced infertility. Wistar-Imamichi strain male and female rats (7 weeks of age) were fed either a standard diet (10% calories from fat) or high-fat diet (45% calories from fat) for 4 months. In male rats, the HFD caused a significant suppression of Kiss1(encoding kisspeptin), Tac3(encoding neurokinin B), and Pdyn(encoding dynorphin A) gene expression in the ARC, resulting in a decrease in plasma luteinizing hormone (LH) levels. In female rats, 58% of the HFD-fed female rats exhibited irregular estrous cycles, while the other rats showed regular cycles. LH pulses were found, and the numbers of ARC Kiss1-,Tac3-, and Pdyn-expressing cells were high in control animals and almost allHFD-fed female rats, but two out of 10 rats showed profound HFD-induced suppression of LH pulse frequency and reduction in these cells. No statistical differences in LH secretion or ARC KNDy gene expression were observed between HFD-fed and control female rats. Additionally, the number of Gnrh1-expressing cells in the preoptic area was comparable between the groups in both sexes. Our findings revealed that HFD-fed male rats showed KNDy-dependent infertility, while irregular menstruation was mainly induced by KNDy-independent pathways during the incipient stage of obese infertility in female rats. Taken together, hypothalamic kisspeptin neurons in male rats may be susceptible to HFD-induced obesity compared with those in female rats.

scholarly journals Retinoic acid stimulates annexin-mediated growth plate chondrocyte mineralization

2002 ◽  
Vol 157 (6) ◽  
pp. 1061-1070 ◽  
Author(s):  
Wei Wang ◽  
Thorsten Kirsch
Keyword(s):  
Gene Expression ◽  
Alkaline Phosphatase ◽  
Retinoic Acid ◽  
Growth Plate ◽  
Calcium Concentration ◽  
Matrix Vesicles ◽  
Cytosolic Calcium ◽  
Annexin Ii ◽  
Growth Plate Chondrocytes ◽  
Cytosolic Calcium Concentration

Biomineralization is a highly regulated process that plays a major role during the development of skeletal tissues. Despite its obvious importance, little is known about its regulation. Previously, it has been demonstrated that retinoic acid (RA) stimulates terminal differentiation and mineralization of growth plate chondrocytes (Iwamoto, M., I.M. Shapiro, K. Yagumi, A.L. Boskey, P.S. Leboy, S.L. Adams, and M. Pacifici. 1993. Exp. Cell Res. 207:413–420). In this study, we provide evidence that RA treatment of growth plate chondrocytes caused a series of events eventually leading to mineralization of these cultures: increase in cytosolic calcium concentration, followed by up-regulation of annexin II, V, and VI gene expression, and release of annexin II–, V–, VI– and alkaline phosphatase–containing matrix vesicles. Cotreatment of growth plate chondrocytes with RA and BAPTA-AM, a cell permeable Ca2+ chelator, inhibited the up-regulation of annexin gene expression and mineralization of these cultures. Interestingly, only matrix vesicles isolated from RA-treated cells that contained annexins, were able to take up Ca2+ and mineralize, whereas vesicles isolated from untreated or RA/BAPTA-treated cells, that contained no or only little annexins were not able to take up Ca2+ and mineralize. Cotreatment of chondrocytes with RA and EDTA revealed that increases in the cytosolic calcium concentration were due to influx of extracellular calcium. Interestingly, the novel 1,4-benzothiazepine derivative K-201, a specific annexin Ca2+ channel blocker, or antibodies specific for annexin II, V, or VI inhibited the increases in cytosolic calcium concentration in RA-treated chondrocytes. These findings indicate that annexins II, V, and VI form Ca2+ channels in the plasma membrane of terminally differentiated growth plate chondrocytes and mediate Ca2+ influx into these cells. The resulting increased cytosolic calcium concentration leads to a further up-regulation of annexin II, V, and VI gene expression, the release of annexin II–, V–, VI– and alkaline phosphatase–containing matrix vesicles, and the initiation of mineralization by these vesicles.

scholarly journals Effect of selected endocrine disruptors on gene expression and male urogenital system development in male rats.

2012 ◽  
Vol 31 (1) ◽  
Author(s):  
Sean M. Patrick ◽  
C. De Jager ◽  
M.S. Bornman ◽  
Annie M. Joubert
Keyword(s):  
Gene Expression ◽  
Endocrine Disruptors ◽  
System Development ◽  
Endocrine Disrupting Chemicals ◽  
Male Rats ◽  
Urogenital System ◽  
Endocrine Disrupting ◽  
The Relationship

Endocrine disrupting chemicals may disrupt hormonal processesleading to impaired development. The studies aim was to investigate the relationship betweenvarious EDC exposures and development of urogenital system in male rats across twogenerations.

scholarly journals Transcriptome profiling revealed early vascular smooth muscle cell gene activation following focal ischemic stroke in female rats – comparisons with males

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Mimmi Rehnström ◽  
Simona Denise Frederiksen ◽  
Saema Ansar ◽  
Lars Edvinsson
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Ischemic Stroke ◽  
Differentially Expressed Genes ◽  
Differentially Expressed ◽  
Female Rats ◽  
Male Rats ◽  
Clinical Population ◽  
Regulation Of Transcription ◽  
Stroke Incidence

Abstract Background Women account for 60% of all stroke deaths and are more often permanently disabled than men, despite their higher observed stroke incidence. Considering the clinical population affected by stroke, an obvious drawback is that many pre-clinical and clinical studies only investigate young males. To improve therapeutic translation from bench to bedside, we believe that it is advantageous to include both sexes in experimental models of stroke. The aims of this study were to identify early cerebral vascular responses to ischemic stroke in females, compare the differential gene expression patterns with those seen in males, and identify potential new therapeutic targets. Results Transient middle cerebral artery occlusion (tMCAO) was used to induce stroke in both female and male rats, the middle cerebral arteries (MCAs) were isolated 3 h post reperfusion and RNA was extracted. Affymetrix whole transcriptome expression profiling was performed on female (n = 12) MCAs to reveal differentially expressed genes. In total, 1076 genes had an increased expression and 879 genes a decreased expression in the occluded MCAs as compared with the control MCAs from female rats. An enrichment of genes related to apoptosis, regulation of transcription, protein autophosphorylation, inflammation, oxidative stress, and tissue repair and recovery were seen in the occluded MCA. The high expression genes chosen for qPCR verification (Adamts4, Olr1, JunB, Fosl1, Serpine1, S1pr3, Ccl2 and Socs3) were all shown to be upregulated in the same manner in both females and males after tMCAO (p < 0.05; n = 23). When comparing the differentially expressed genes in female MCAs (occluded and non-occluded) with our previous findings in males after tMCAO, a total of 297 genes overlapped (all groups had 32 genes in common). Conclusions The cascades of processes initiated in the vasculature following reperfusion are complex. Dynamic gene expression alterations were observed in the occluded MCAs, and to a less pronounced degree in the non-occluded MCAs. Dysregulation of inflammation and blood-brain barrier breakdown are possible pharmacological targets. The sample of genes (< 1% of the differentially expressed genes) validated for this microarray did not reveal any sex differences. However, sex differences might be observed for other gene targets.

scholarly journals Transcriptome Profiling Revealed Early Vascular Smooth Muscle Cell Gene Activation Following Focal Ischemic Stroke in Female Rats – Comparisons with Males

2020 ◽  
Author(s):  
Mimmi Rehnström ◽  
Simona Denise Frederiksen ◽  
Lars Edvinsson
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Ischemic Stroke ◽  
Differentially Expressed Genes ◽  
Differentially Expressed ◽  
Female Rats ◽  
Male Rats ◽  
Clinical Population ◽  
Regulation Of Transcription ◽  
Stroke Incidence

Abstract Background. Women account for 60% of all stroke deaths and are more often permanently disabled than men, despite their higher observed stroke incidence. Considering the clinical population affected by stroke, an obvious drawback is that many pre-clinical and clinical studies only investigate young males. To improve therapeutic translation from bench to bedside, we believe that it is advantageous to include both sexes in experimental models of stroke. The aims of this study were to identify early cerebral vascular responses to ischemic stroke in females, compare the differential gene expression patterns with those seen in males, and identify potential new therapeutic targets.Results. Transient middle cerebral artery occlusion (tMCAO) was used to induce stroke in both female and male rats, the middle cerebral arteries (MCAs) were isolated 3 hours post reperfusion and RNA was extracted. Affymetrix whole transcriptome expression profiling was performed on female MCAs to reveal differentially expressed genes. In total, 1076 genes had an increased expression and 879 genes a decreased expression in the occluded MCA as compared to the non-stroke control arteries from female rats. An enrichment of genes related to apoptosis, regulation of transcription, protein autophosphorylation, inflammation, oxidative stress, and tissue repair and recovery were seen in the occluded MCA. The high expression genes chosen for qPCR verification (Adamts4, Olr1, JunB, Fosl1, Serpine1, S1pr3, Ccl2 and Socs3) were all shown to be upregulated in the same manner in both females and males after tMCAO (p < 0.05). When comparing the differentially expressed genes in female MCAs (occluded and non-occluded) with our previous findings in males after tMCAO, a total of 297 genes overlapped (all groups had 32 genes in common).Conclusions. The cascades of processes initiated in the vasculature following reperfusion are complex. Dynamic gene expression alterations were observed in the occluded MCA, and to a less pronounced degree in the non-occluded MCA. Dysregulation of inflammation and blood-brain barrier breakdown are possible pharmacological targets. The sample of genes (<1% of the differentially expressed genes) validated for this microarray did not reveal any sex differences. However, sex differences might be observed for other gene targets.

scholarly journals Effect of Eight Weeks Aerobic Exercise and Vitamin-D Supplementation on Osteocalcin and Alkaline Phosphatase Gene Expression in Male Rats Poisoned with Hydrogen Peroxide

2021 ◽  
Author(s):  
Ramin Eimari Eskandari ◽  
Hassan Matin Homaee ◽  
Lida Moradi
Keyword(s):  
Gene Expression ◽  
Hydrogen Peroxide ◽  
Vitamin D ◽  
Alkaline Phosphatase ◽  
Aerobic Exercise ◽  
Bone Tissue ◽  
Interactive Effect ◽  
Systemic Effect ◽  
Vitamin D Supplementation ◽  
Male Rats

Introduction: Free radicals increase with age and disease, so the aim of this study was to investigate the effect of exercise and vitamin D on the expression of alkaline phosphatase and osteocalcin genes in bone tissue of rats poisoned with hydrogen peroxide. Methods: In this experimental trial, 36 adult male Wistar rats were randomized into six groups of six rats, 1) control; 2) hydrogen peroxide; 3) hydrogen peroxide + vitamin D; 4) hydrogen peroxide + exercise; 5) hydrogen peroxide + exercise and vitamin D and 6) Sham. For eight weeks, groups 2, 3, 4, and 5 were given daily dose of 1 mmol/kg hydrogen peroxide on even days, groups 3 and 5 received 0.5 mg / kg of Vitamin-D daily, and sham group received only vitamin D solvent intraperitoneally. Groups 4 and 5 performed aerobic exercise 3 day/week. Osteocalcin and alkaline phosphatase gene expression were measured by PCR and were analyzed using independent t-test, two-way analysis of variance and Boferroni’s post hoc test with SPSS 16 (p≤0.05). Results: The interactive effect of exercise and vitamin D on increasing alkaline phosphatase and osteocalcin was significant. (p≤0.05); exercise increased alkaline phosphatase and osteocalcin (p ≤ 0.05); vitamin D was also associated with increased alkaline phosphatase and osteocalcin (p=0.0001). The greatest effect on increasing osteocalcin and alkaline phosphatase showed in groups 5 and 3, respectively (p=0.001). Conclusion: Exercise and vitamin D had a positive effect on bone tissue, so that even the systemic effect of hydrogen peroxide could not change the results of this constructive effect.

scholarly journals Effect of sex on glucose handling by adipocytes isolated from rat subcutaneous, mesenteric and perigonadal adipose tissue

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5440 ◽  
Author(s):  
Floriana Rotondo ◽  
Ana Cecilia Ho-Palma ◽  
Xavier Remesar ◽  
José Antonio Fernández-López ◽  
María del Mar Romero ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Glucose Consumption ◽  
Female Rats ◽  
Male Rats ◽  
Release Rates ◽  
Initial Glucose Concentration ◽  
Adult Rat ◽  
Carbon Substrates

BackgroundAdult rat epididymal adipocytes are able to convert large amounts of glucose to lactate and glycerol. However, fatty acid efflux is much lower than that expected from glycerol levels if they were the product of lipolysis. Use of glucose for lipogenesis is limited, in contrast with the active glycolysis-derived lactate (and other 3-carbon substrates). In this study, we analyzed whether white adipose tissue (WAT) site and sex affect these processes.MethodsMature adipocytes from perigonadal, mesenteric and subcutaneous WAT of female and male rats were isolated, and incubated with 7 or 14 mM glucose during 1 or 2 days. Glucose consumption, metabolite efflux and gene expression of glycolytic and lipogenesis-related genes were measured.ResultsThe effects of medium initial glucose concentration were minimal on most parameters studied. Sex-induced differences that were more extensive; however, the most marked, distinct, effects between WAT sites, were dependent on the time of incubation. In general, the production of lactate was maintained during the incubation, but glycerol release rates increased with time, shifting from a largely glycolytic origin to its triacylglycerol (TAG) lipolytic release. Glycerol incorporation was concurrent with increased TAG turnover: lipolytic glycerol was selectively secreted, while most fatty acids were recycled again into TAG. Fatty acid efflux increased with incubation, but was, nevertheless, minimal compared with that of glycerol. Production of lactate and glycerol from glucose were maximal in mesenteric WAT.DiscussionFemale rats showed a higher adipocyte metabolic activity than males. In mesenteric WAT, gene expression (and substrate efflux) data suggested that adipocyte oxidation of pyruvate to acetyl-CoA was higher in females than in males, with enhanced return of oxaloacetate to the cytoplasm for its final conversion to lactate. WAT site differences showed marked tissue specialization-related differences. Use of glucose for lipogenesis was seriously hampered over time, when TAG turnover-related lipolysis was activated. We postulate that these mechanisms may help decrease glycaemia and fat storage, producing, instead, a higher availability of less-regulated 3-carbon substrates, used for energy elsewhere.

scholarly journals Pdx1 inactivation restricted to the intestinal epithelium in mice alters duodenal gene expression in enterocytes and enteroendocrine cells

2009 ◽  
Vol 297 (6) ◽  
pp. G1126-G1137 ◽  
Author(s):  
Chin Chen ◽  
Rixun Fang ◽  
Corrine Davis ◽  
Charalambos Maravelias ◽  
Eric Sibley
Keyword(s):  
Gene Expression ◽  
Alkaline Phosphatase ◽  
Small Intestine ◽  
Intestinal Epithelium ◽  
Mouse Strain ◽  
Paneth Cell ◽  
Cell Number ◽  
Enteroendocrine Cells ◽  
Mrna Abundance ◽  
Proximal Small Intestine

Null mutant mice lacking the transcription factor pancreatic and duodenal homeobox 1 (Pdx1) are apancreatic and survive only a few days after birth. The role of Pdx1 in regulating intestinal gene expression has therefore yet to be determined in viable mice with normal pancreatic development. We hypothesized that conditional inactivation of Pdx1 restricted to the intestinal epithelium would alter intestinal gene expression and cell differentiation. Pdx1 flox/flox; VilCre mice with intestine-specific Pdx1 inactivation were generated by crossing a transgenic mouse strain expressing Cre recombinase, driven by a mouse villin 1 gene promoter fragment, with a mutant mouse strain homozygous for loxP site-flanked Pdx1. Pdx1 protein is undetectable in all epithelial cells in the intestinal epithelium of Pdx1 flox/flox; VilCre mice. Goblet cell number and mRNA abundance for mucin 3 and mucin 13 genes in the proximal small intestine are comparable between Pdx1 flox/flox; VilCre and control mice. Similarly, Paneth cell number and expression of Paneth cell-related genes Defa1, Defcr-rs1, and Mmp7 in the proximal small intestine remain statistically unchanged by Pdx1 inactivation. Although the number of enteroendocrine cells expressing chromogranin A/B, gastric inhibitory polypeptide (Gip), or somatostatin (Sst) is unaffected in the Pdx1 flox/flox; VilCre mice, mRNA abundance for Gip and Sst is significantly reduced in the proximal small intestine. Conditional Pdx1 inactivation attenuates intestinal alkaline phosphatase (IAP) activity in the duodenal epithelium, consistent with an average 91% decrease in expression of the mouse enterocyte IAP gene, alkaline phosphatase 3 (a novel Pdx1 target candidate), in the proximal small intestine following Pdx1 inactivation. We conclude that Pdx1 is necessary for patterning appropriate gene expression in enterocytes and enteroendocrine cells of the proximal small intestine.

Abstract 078: Postnatal Treatment with Metyrapone Attenuates the Effects of Early Life Stress (ELS) on Diet-induced Obesity in Female Rats

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Margaret O Murphy ◽  
Dianne M Cohn ◽  
Analia S Loria
Keyword(s):  
Gene Expression ◽  
Visceral Fat ◽  
Early Life ◽  
Plasma Corticosterone ◽  
Female Rats ◽  
Male Rats ◽  
Female Rat ◽  
Diet Induced Obesity ◽  
Postnatal Treatment ◽  
Obesogenic Diet

Clinical studies have shown a positive correlation between ELS and the development of cardiometabolic disease, particularly affecting women. We previously reported that male rats exposed to Maternal Separation (MatSep), a model of ELS in rodents, do not develop exaggerated diet-induced obesity. Thus, this study tested the hypothesis that MatSep exacerbates the response to an obesogenic diet in female rats. Also, we tested whether the postnatal treatment with metyrapone (MTP), a corticosterone synthase inhibitor, would attenuate this phenotype. MatSep was performed in WKY offspring during 3 hours/day from postnatal days 2-14. Non-disturbed littermates were used as controls. Female rat offspring were untreated or treated with MTP (50 mg/kg, i.p.), 30 minutes prior the daily separation. Upon weaning, rats were placed on regular chow (ND, 18% kcal fat) or HFD (60% kcal fat) for 12 weeks. Despite no differences in food intake (metabolism cages) and blood pressure (DSI radiotelemetry) MatSep exaggerated body weight gain and fat pad weights (p<0.05) in response to HFD. Also, MatSep increased plasma corticosterone (189±48 vs. 79±18 pg/ml, p<0.05) and leptin (2.1±0.4 vs. 1.5±0.4 ng/ml, p<0.05) levels compared to control while insulin and adiponectin levels were similar between groups. Oral glucose tolerance test was impaired in MatSep rats showing a greater AUC compared to control rats (p<0.05). Importantly, MTP-treated female MatSep rats showed significantly attenuated diet-induced obesity, glucose intolerance, plasma corticosterone and leptin levels. Histological analysis revealed that MTP treatment ameliorated the adipocyte size in visceral fat from MatSep rats as well (p<0.05). Gene expression in liver indicated that glucose 6 phospatase, but not other gluconeogenic enzymes, were increased in obese MatSep rats, whereas the MTP treatment abrogated this effect. The visceral fat gene expression showed lower levels of insulin receptor in MatSep rats, but no differences in other genes related to the glucose disposal. Overall, these data reveal that female MatSep rats display a greater susceptibility for the synergistic effect between obesogenic diet and ELS compared to male rats, and this effect may be linked to early life exposure to stress hormones.

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