Maternal High-Fat Diet During Pregnancy and Lactation has Opposite Effects on Gonadal Expression of Leptin and Leptin Receptor in Rat Dams and Their Offspring

2017 ◽  
Vol 49 (09) ◽  
pp. 707-715 ◽  
Author(s):  
Agnieszka Rak ◽  
Anna Hejmej ◽  
Monika Słupecka-Ziemilska ◽  
Jaroslaw Woliński ◽  
Elzbieta Fiedor ◽  
...  

AbstractThis study investigated the effect of a high-fat (HF) diet on protein expression of leptin and its receptor in the gonads of dams and their offspring. Female Wistar rats were fed a HF diet (30% fat) or a standard breeding (BD) diet (5% fat) during pregnancy and lactation. At 21 days of lactation, mothers and both sexes of prepubertal offspring were killed by decapitation. The protein expression of leptin and its receptor was assayed by Western blot and immunohistochemistry in gonadal, periovarian, and epididymal white adipose tissue (WAT). We demonstrated that leptin protein expression in ovary, and both leptin and ObRb expression in periovarian WAT was decreased in HF dams compared with BD animals. Immunohistochemistry showed lower leptin expression in growing antral follicles and corpora lutea of HF dams. Conversely, in both gonads and epididymal WAT of HF offspring, leptin and its receptor were significantly higher expressed compared with BD. Immunolocalization of leptin system in HF offspring gonads showed higher expression in growing and antral follicles of the ovary, seminiferous tubules, and interstitial tissue of testes. In conclusion, high gonadal and gonadal-WAT expression of leptin system was observed in the offspring of dams fed a HF diet during pregnancy and lactation.

2010 ◽  
Vol 1 (4) ◽  
pp. 245-254 ◽  
Author(s):  
K. L. Connor ◽  
M. H. Vickers ◽  
C. Cupido ◽  
E. Sirimanne ◽  
D. M. Sloboda

We previously reported that a maternal high fat (HF) diet resulted in adult offspring with increased adiposity and hyperleptinemia. As leptin has an inhibitory effect on adrenal steroidogenesis and a stimulatory effect on epinephrine synthesis, we hypothesized that key adrenal steroidogenic and catecholaminergic enzymes would be altered in these offspring. Wistar rats were randomized into three groups at weaning: (1) control dams fed a standard control chow diet from weaning and throughout pregnancy and lactation (CON), (2) dams fed a HF diet from weaning and throughout pregnancy and lactation (MHF) and (3) dams fed standard control chow diet throughout life until conception, then fed a HF diet in pregnancy and lactation (PLHF). Dams were mated at day 100 (P100). After birth at P22 (weaning), male offspring were fed a standard control chow (con) or high fat (hf) diet. At P160, plasma samples and adrenal tissues were collected. Postweaning hf diet significantly elevated plasma corticosterone concentrations in PLHF-hf offspring compared to PLHF-con. MHF nutrition increased adrenal adrenocorticotrophic hormone receptor (ACTH-R) mRNA levels compared to CON-con. 3β-hydroxysteroid dehydrogenase (3βHSD) mRNA levels were decreased in MHF compared to PLHF offspring. Phenylethanolamine N-methyltransferase (PNMT) mRNA levels were increased in MHF-hf offspring compared to MHF-con. Plasma homocysteine (HCY) concentrations were significantly elevated in CON-hf and MHF-hf offspring compared to chow-fed offspring, associated with elevated intakes of methionine and reduced intakes of pyridoxine. Immunoreactive leptin receptor (ObRb) and PNMT were colocalized in medullary chromaffin cells. This study suggests that a postweaning HF diet in offspring induced changes in adrenal gene expression levels that are dependent upon the level of maternal nutrition.


2017 ◽  
Vol 49 (09) ◽  
pp. e2-e2
Author(s):  
Agnieszka Rak ◽  
Anna Hejmej ◽  
Monika Słupecka-Ziemilska ◽  
Jaroslaw Woliński ◽  
Elzbieta Fiedor ◽  
...  

2005 ◽  
Vol 34 (2) ◽  
pp. 489-503 ◽  
Author(s):  
Thomas P Meehan ◽  
Barry G Harmon ◽  
Megan E Overcast ◽  
Kristine K Yu ◽  
Sally A Camper ◽  
...  

To study the effects of premature and chronic ligand-mediated luteinizing hormone receptor (LHR) activation on reproductive development, we have generated transgenic mice expressing a genetically engineered, constitutively active yoked hormone–receptor complex (YHR), in which a fusion protein of human chorionic gonadotropin (hCG) is covalently linked to the N-terminus of rat LHR. YHR-expressing mice (YHR+) were analyzed at pre- and post-pubertal ages. Relative to wild type (WT) controls, male mice exhibited prepubertal increases in testosterone levels and seminal vesicle weights, and decreases in serum FSH, serum LH, testes weight, and the size of the seminiferous tubules. In adult male YHR+ mice, testosterone and LH levels are not significantly different from WT controls. However, FSH levels and testes weights remain decreased. Female YHR+ mice undergo precocious puberty with early vaginal opening, accelerated uterine development, enhanced follicular development, including the presence of corpora lutea, and an increase in serum progesterone. At 12 weeks of age, the ovary exhibits a relative increase in the amount of interstitial tissue, comprised of cells that are hypertrophic and luteinized, as well as follicles that are degenerating. Additionally, hemorrhagic cysts develop in approximately 25% of the transgenic mice. These degenerative changes are consistent with an aging ovary suggesting that CG-induced LHR activation in female mice leads to precocious sexual development and ovarian lesions. Taken together, these data indicate that the single chain YHR is functional in vivo and demonstrate that YHR+ mice provide a novel system to further understand the reproductive consequences of aberrant LHR activation.


Endocrinology ◽  
2013 ◽  
Vol 154 (6) ◽  
pp. 2188-2199 ◽  
Author(s):  
Shweta Sharma ◽  
Hidetaka Morinaga ◽  
Vicky Hwang ◽  
WuQiang Fan ◽  
Marina O. Fernandez ◽  
...  

Abstract Female obesity is associated with insulin resistance, hyperandrogenemia, and reproductive dysfunction. We hypothesized that elevated free fatty acids (FFAs) might directly modulate pituitary gonadotropin production. FFAs caused a time- and dose-dependent increase in phosphorylation of the MAPKs p38MAPK, c-Jun N-terminal kinase (JNK)-1/2, and ERK1/2 in LβT2 gonadotrope cells. Furthermore, FFAs up-regulated Lhb mRNA expression acutely, an effect that was blocked by JNK inhibition, but suppressed Fshb mRNA expression, an effect that was independent of MAPK signaling. FFAs enhanced the activation of the MAPKs in the presence of GnRH, although the cotreatment did not alter Lhb induction but did eliminate the GnRH induction of Fshb. FFAs also suppressed activin-induced Fshb expression. Knockdown experiments showed that the FFA effect on the inflammatory kinases p38MAPK and JNK and on Lhb, but not Fshb, mRNA expression is mediated via toll-like receptor-2 and toll-like receptor-4 and was mimicked by lipopolysaccharide stimulation. In vivo, male C57BL/6 mice on a high-fat diet showed reduced FSH levels consistent with the suppression of Fshb seen in vitro. Histological analysis of the testes showed an increased number of abnormal seminiferous tubules. Female mice on a high-fat diet lacked the expected proestrus LH and FSH surge and exhibited an increase in the number of days at estrus and a reduced number of days at proestrus, and ovaries had significantly fewer corpora lutea. Taken together, our findings suggest that lipid excess can lead to reproductive defects in both male and female mice.


2021 ◽  
Vol 38 (2) ◽  
pp. 99-106
Author(s):  
Javad SADEGHINEZHAD ◽  
Moslem DAHMARDEH ◽  
Zahra TOOTIAN ◽  
Hadis BOJARZADEH ◽  
Fatemeh YARMAHMOUDI

Oxaliplatin (Ox) is widely used for the treatment of various tumors. Since Ox prevents DNA replication and transcription, it may affect organs with rapid cell divisions such as the testes. Although its use during pregnancy has been reported, no information regarding its effects on the testes of the offspring is not available yet. Thirty-two mice were randomly divided into four groups. The control group (1) was administered intraperitoneally 0.2 ml of saline three times a week for the 21 days of pre-pregnancy, pregnancy and lactation. Experimental groups 2, 3 and 4 received 3 mg/kg of oxaliplatin three times a week for 21 days during pre-pregnancy, pregnancy and lactation, respectively. The left testis was removed from male offspring 30 and 60 days after birth. The volume of the testes, seminiferous tubules and interstitial tissue, the surface area and height of the seminiferous epithelium, as well as the length and diameter of seminiferous tubules, were analyzed by means of stereology. Results showed a decrease in the evaluated parameters in experimental groups, in comparison with the control group. Due to the ameliorating effect of Ox on offspring testes, cautiousness is needed during maternal administration in order to preserve the fertility of male offspring.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Graham J. Howie ◽  
Deborah M. Sloboda ◽  
Clare M. Reynolds ◽  
Mark H. Vickers

Objective.Offspring born to mothers either fed an obesogenic diet throughout their life or restricted to pregnancy and lactation demonstrate obesity, hyperinsulinemia, and hyperleptinemia, irrespective of their postweaning diet. We examined whether timing of a maternal obesogenic diet results in differential regulation of pancreatic adipoinsular and inflammatory signaling pathways in offspring.Methods.Female Wistar rats were randomized into 3 groups: (1) control (CONT): fed a control diet preconceptionally and during pregnancy and lactation; (2) maternal high fat (MHF): fed an HF diet throughout their life and during pregnancy and lactation; (3) pregnancy and lactation HF (PLHF): fed a control diet throughout life until mating, then HF diet during pregnancy and lactation. Male offspring were fed the control diet postweaning. Plasma and pancreatic tissue were collected, and mRNA concentrations of key factors regulating adipoinsular axis signaling were determined.Results.MHF and PLHF offspring exhibited increased adiposity and were hyperinsulinemic and hyperleptinemic compared to CONT. Despite a similar anthropometric phenotype, MHF and PLHF offspring exhibited distinctly different expression for key pancreatic genes, dependent upon maternal preconceptional nutritional background.Conclusions.These data suggest that despite using differential signaling pathways, obesity in offspring may be an adaptive outcome of early life exposure to HF during critical developmental windows.


2021 ◽  
Vol 14 (1) ◽  
pp. 52
Author(s):  
Kirsty Hamilton ◽  
Jenni Harvey

It is widely accepted that the endocrine hormone leptin controls food intake and energy homeostasis via activation of leptin receptors expressed on hypothalamic arcuate neurons. The hippocampal formation also displays raised levels of leptin receptor expression and accumulating evidence indicates that leptin has a significant impact on hippocampal synaptic function. Thus, cellular and behavioural studies support a cognitive enhancing role for leptin as excitatory synaptic transmission, synaptic plasticity and glutamate receptor trafficking at hippocampal Schaffer collateral (SC)-CA1 synapses are regulated by leptin, and treatment with leptin enhances performance in hippocampus-dependent memory tasks. Recent studies indicate that hippocampal temporoammonic (TA)-CA1 synapses are also a key target for leptin. The ability of leptin to regulate TA-CA1 synapses has important functional consequences as TA-CA1 synapses are implicated in spatial and episodic memory processes. Moreover, degeneration is initiated in the TA pathway at very early stages of Alzheimer’s disease, and recent clinical evidence has revealed links between plasma leptin levels and the incidence of Alzheimer’s disease (AD). Additionally, accumulating evidence indicates that leptin has neuroprotective actions in various AD models, whereas dysfunctions in the leptin system accelerate AD pathogenesis. Here, we review the data implicating the leptin system as a potential novel target for AD, and the evidence that boosting the hippocampal actions of leptin may be beneficial.


2021 ◽  
pp. 2100065
Author(s):  
Zhen Li ◽  
Viola J. Kosgei ◽  
Anais Bison ◽  
Jean‐Marc Alberto ◽  
Remi Umoret ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Safia Akhtar ◽  
Silas A. Culver ◽  
Helmy M. Siragy

AbstractRecent studies suggested that renal gluconeogenesis is substantially stimulated in the kidney in presence of obesity. However, the mechanisms responsible for such stimulation are not well understood. Recently, our laboratory demonstrated that mice fed high fat diet (HFD) exhibited increase in renal Atp6ap2 [also known as (Pro)renin receptor] expression. We hypothesized that HFD upregulates renal gluconeogenesis via Atp6ap2-PGC-1α and AKT pathway. Using real-time polymerase chain reaction, western blot analysis and immunostaining, we evaluated renal expression of the Atp6ap2 and renal gluconeogenic enzymes, PEPCK and G6Pase, in wild type and inducible nephron specific Atp6ap2 knockout mice fed normal diet (ND, 12 kcal% fat) or a high-fat diet (HFD, 45 kcal% fat) for 8 weeks. Compared with ND, HFD mice had significantly higher body weight (23%) (P < 0.05), renal mRNA and protein expression of Atp6ap2 (39 and 35%), PEPCK (44 and 125%) and G6Pase (39 and 44%) respectively. In addition, compared to ND, HFD mice had increased renal protein expression of PGC-1α by 32% (P < 0.05) and downregulated AKT by 33% (P < 0.05) respectively in renal cortex. Atp6ap2-KO abrogated these changes in the mice fed HFD. In conclusion, we identified novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway.


2011 ◽  
Vol 106 (4) ◽  
pp. 491-501 ◽  
Author(s):  
Manar Aoun ◽  
Francoise Michel ◽  
Gilles Fouret ◽  
Audrey Schlernitzauer ◽  
Vincent Ollendorff ◽  
...  

Accumulation of muscle TAG content and modification of muscle phospholipid fatty acid pattern may have an impact on lipid metabolism, increasing the risk of developing diabetes. Some polyphenols have been reported to modulate lipid metabolism, in particular those issued from red grapes. The present study was designed to determine whether a grape polyphenol extract (PPE) modulates skeletal muscle TAG content and phospholipid fatty acid composition in high-fat–high-sucrose (HFHS) diet-fed rats. Muscle plasmalemmal and mitochondrial fatty acid transporters, GLUT4 and lipid metabolism pathways were also explored. The PPE decreased muscle TAG content in HFHS/PPE diet-fed rats compared with HFHS diet-fed rats and induced higher proportions of n-3 PUFA in phospholipids. The PPE significantly up-regulated GLUT4 mRNA expression. Gene and protein expression of muscle fatty acid transporter cluster of differentiation 36 (CD36) was increased in HFHS diet-fed rats but returned to control values in HFHS/PPE diet-fed rats. Carnitine palmitoyltransferase 1 protein expression was decreased with the PPE. Mitochondrial β-hydroxyacyl CoA dehydrogenase was increased in HFHS diet-fed rats and returned to control values with PPE supplementation. Lipogenesis, mitochondrial biogenesis and mitochondrial activity were not affected by the PPE. In conclusion, the PPE modulated membrane phospholipid fatty acid composition and decreased muscle TAG content in HFHS diet-fed rats. The PPE lowered CD36 gene and protein expression, probably decreasing fatty acid transport and lipid accumulation within skeletal muscle, and increased muscle GLUT4 expression. These effects of the PPE are in favour of a better insulin sensibility.


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