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

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.

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DNA microarray analysis reveals differential gene expression in the soleus muscle between male and female rats exposed to a high fat diet

Molecular Biology Reports ◽

10.1007/s11033-012-1486-2 ◽

2012 ◽

Vol 39 (6) ◽

pp. 6569-6580 ◽

Cited By ~ 6

Author(s):

Tae Seok Oh ◽

Jong Won Yun

Keyword(s):

Gene Expression ◽

Differential Gene Expression ◽

Microarray Analysis ◽

Dna Microarray ◽

High Fat Diet ◽

Female Rats ◽

High Fat ◽

Male And Female ◽

Male And Female Rats ◽

Differential Gene

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Study on the Optimization and Stability of Single-dose Streptozotocin-induced Diabetic Modelling in Rats

10.21203/rs.3.rs-310098/v1 ◽

2021 ◽

Author(s):

Yao Zhang ◽

Jiao Zhang ◽

Ming Hong ◽

Jingyi Huang ◽

Rui Wang ◽

...

Keyword(s):

Blood Glucose ◽

High Fat Diet ◽

Female Rats ◽

Male Rats ◽

Control Group ◽

High Fat ◽

Male And Female ◽

Glucose Levels ◽

Male And Female Rats ◽

And Control

Abstract Aim: This study was performed to optimize the experimental conditions in streptozotocin (STZ)-induced diabetic model by using Sprague-Dawley (SD) rats to evaluate the stability of the model.Methods: In addition to the control group, the male and female SD rats were randomly divided into the following treatment groups (with six rats per group): STZ 45 (45 mg/kg STZ); STZ 65 (65 mg/kg STZ); STZ 85 (85 mg/kg STZ); high-fat diet with STZ 45; high-fat diet with STZ 65; and high-fat diet with STZ 85. Changes in the body weight and blood glucose were observed dynamically. Results: No significant differences were found in the blood glucose or body weight between the STZ 45 and control groups in both male and female rats, whether or not the rats were on a high-fat diet. However, significant differences were found in the blood glucose between the high-dose STZ and control groups in both male and female rats, regardless of whether the rats were on a high-fat diet or not (P<0.05 or P<0.01). Compared with the control group, significant differences in the blood glucose levels (P<0.05 or P<0.01) and higher blood glucose levels were found in the male rats fed with normal diet than those of rats fed with high-fat diet.Conclusions: In this study, male rats fed with ordinary feed and injected with 65 mg/kg STZ were the most stable and ideal diabetic rats.

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High-fat diet-induced hypertension is associated with a proinflammatory T cell profile in male and female Dahl salt-sensitive rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00389.2018 ◽

2018 ◽

Vol 315 (6) ◽

pp. H1713-H1723 ◽

Cited By ~ 13

Author(s):

Lia E. Taylor ◽

Ellen E. Gillis ◽

Jacqueline B. Musall ◽

Babak Baban ◽

Jennifer C. Sullivan

Keyword(s):

T Cells ◽

T Cell ◽

Regulatory T Cells ◽

High Fat Diet ◽

Female Rats ◽

Male Rats ◽

High Fat ◽

Male And Female ◽

The Impact ◽

Cell Profile

Evidence supports a sex difference in the impact of a high-fat diet (HFD) on cardiovascular outcomes, with male experimental animals exhibiting greater increases in blood pressure (BP) than female experimental animals. The immune system has been implicated in HFD-induced increases in BP, and there is a sex difference in T-cell activation in hypertension. The goal of this study was to determine the impact of HFD on BP and aortic and renal T cell profiles in male and female Dahl salt-sensitive (DSS) rats. We hypothesized that male DSS rats would have greater increases in BP and T cell infiltration in response to a HFD compared with female DSS rats. BP was measured by tail-cuff plethysmography, and aortic and renal T cells were assessed by flow cytometric analysis in male and female DSS rats on a normal-fat diet (NFD) or HFD from 12 to 16 wk of age. Four weeks of HFD increased BP in male and female DSS rats to a similar degree. Increases in BP were accompanied by increased percentages of CD4+ T cells and T helper (Th)17 cells in both sexes, although male rats had more proinflammatory T cells. Percentages of renal CD3+ and CD4+ T cells as well as Th17 cells were increased in both sexes by the HFD, although the increase in CD3+ T cells was greater in male rats. HFD also decreased the percentage of aortic and renal regulatory T cells in both sexes, although female rats maintained more regulatory T cells than male rats regardless of diet. In conclusion, both male and female DSS rats exhibit BP sensitivity to a HFD; however, the mechanisms mediating HFD-induced increases in BP may be distinct as male rats exhibit greater increases in the percentage of proinflammatory T cells than female rats. NEW & NOTEWORTHY Our study demonstrates that male and female Dahl salt-sensitive rats exhibit similar increases in blood pressure to a high-fat diet and an increase in aortic and renal T cells. These results are in contrast to studies showing that female rats remain normotensive and/or upregulate regulatory T cells in response to hypertensive stimuli compared with male rats. Our data suggest that a 4-wk high-fat diet has sex-specific effects on the T cell profile in Dahl salt-sensitive rats.

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Long-term High-fat-diet Feeding Impairs Mitochondrial Biogenesis in Liver of Male and Female Rats

Cellular Physiology and Biochemistry ◽

10.1159/000320552 ◽

2010 ◽

Vol 26 (3) ◽

pp. 291-302 ◽

Cited By ~ 47

Author(s):

Antònia Nadal-Casellas ◽

Emilia Amengual-Cladera ◽

Ana María Proenza ◽

Isabel Lladó ◽

Magdalena Gianotti

Keyword(s):

Mitochondrial Biogenesis ◽

High Fat Diet ◽

Female Rats ◽

High Fat ◽

Male And Female ◽

Male And Female Rats

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Study on optimization and stability of a single dose streptozotocin-induced diabetic modeling in rats

10.21203/rs.3.rs-91976/v1 ◽

2020 ◽

Author(s):

Yao Zhang ◽

jiao Zhang ◽

Ming Hong ◽

Jingyi Huang ◽

Rui Wang ◽

...

Keyword(s):

Blood Glucose ◽

High Fat Diet ◽

Female Rats ◽

Male Rats ◽

Control Group ◽

High Fat ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Sd Rats ◽

Male And Female Rats

Abstract BackgroundOptimization of experimental conditions in streptozotocin induced diabetic model in Sprague Dawley (SD) rats to evaluate the stability of the model.MethodsMale and female SD rats were randomly divided into control group, STZ 45 group (STZ: 45 mg / kg), STZ 65 group (STZ: 65 mg / kg), STZ 85 group (STZ: 85 mg / kg), high fat diet with STZ 45 group (STZ: 45 mg / kg), high fat diet with STZ 65 group (STZ: 65 mg / kg), high fat diet with STZ 85 group (STZ: 85 mg / kg). N = 6 in each group. The changes of body weight and blood glucose were observed dynamically.ResultsThere was no significant difference in blood glucose or body weight between the STZ 45 group and the control group in both male and female rats, whether or not they were on a high-fat diet. However, there were significant differences in blood glucose between the high-dose STZ group and the control group in both male and female rats, regardless of whether the rats were on a high-fat diet or not (P < 0.05 or P < 0.01). Compared with the control group, there were significant differences in blood glucose levels (P < 0.05 or P < 0.01) and higher blood glucose levels in the male rats fed with the normal diet than that in those fed with the high-fat diet.ConclusionsIn this study, male rats fed with ordinary feed and injected STZ dose of 65 mg / kg were the most stable and ideal diabetic rat.

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The Effects of Eating a High Fat Diet on Sensitivity of Male and Female Rats to Methamphetamine and Dopamine D1 Receptor Agonist SKF 82958

Journal of Pharmacology and Experimental Therapeutics ◽

10.1124/jpet.119.263293 ◽

2020 ◽

Vol 374 (1) ◽

pp. 6-15

Author(s):

Jeremiah Ramos ◽

Ethan J. Hardin ◽

Alice H. Grant ◽

Grace Flores-Robles ◽

Adrian T. Gonzalez ◽

...

Keyword(s):

High Fat Diet ◽

Receptor Agonist ◽

Dopamine D1 Receptor ◽

D1 Receptor ◽

Female Rats ◽

High Fat ◽

Male And Female ◽

Male And Female Rats ◽

Skf 82958

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Effect of High-fat Diet on Tracheal Responsiveness to Methacholine and Insulin Resistance Index in Ovalbumin-sensitized Male and Female Rats

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v18i1.630 ◽

2019 ◽

Author(s):

Hassan Ghobadi ◽

Mohammad Reza Alipour ◽

Rana Keyhanmanesh ◽

Mohammad Hossein Boskabady ◽

Mohammad Reza Aslani

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

Close Association ◽

Serum Insulin ◽

Resistance Index ◽

Normal Diet ◽

Female Rats ◽

High Fat ◽

Male And Female ◽

Male And Female Rats

Epidemiological and clinical studies have demonstrated a close association between obesity and asthma. The current study investigated the effect of high-fat diet on tracheal responsiveness to methacholine and insulin resistance in ovalbumin (OVA) sensitized male and female rats. The rats were divided into eight groups (n=6 per group): female with the normal diet (F+ND), male with the normal diet (M+ND), female OVA-sensitized with the normal diet (F+SND), male OVA-sensitized with the normal diet (M+SND), female with high-fat diet (F+HFD), male with high-fat diet (M+HFD), female OVA-sensitized with high-fat diet (F+SHFD), and male OVA-sensitized with high-fat diet (M+SHFD). All rats were fed for 8 weeks with high-fat diet or standard pelts, and for another 4 weeks, they were sensitized with OVA or saline. At the end of the study, the tracheal responsiveness to methacholine, serum insulin, and blood glucose levels was measured. Also, insulin resistance indexes were determined. OVA-sensitization and diet-induced obesity caused the curve of methacholine concentration response to shifting to the left. In addition, results indicated that the EC50 (the effective concentration of methacholine generating 50% of peak response) in F+SHFD rats was statistically lower than M+SHFD group (p<0.05). Moreover, insulin resistance was higher in the F+SHFD than the M+SHFD group (p<0.001). These results suggest that insulin resistance and metabolic syndrome may be involved in the pathogenesis of obesity associated with OVA-sensitized rats condition, especially in female animals.

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Energy expenditure in obesity-prone and obesity-resistant rats before and after the introduction of a high-fat diet

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00549.2009 ◽

2010 ◽

Vol 299 (4) ◽

pp. R1097-R1105 ◽

Cited By ~ 33

Author(s):

Matthew R. Jackman ◽

Paul S. MacLean ◽

Daniel H. Bessesen

Keyword(s):

Physical Activity ◽

Weight Gain ◽

Energy Expenditure ◽

Energy Intake ◽

High Fat Diet ◽

Female Rats ◽

High Fat ◽

Male And Female ◽

Male And Female Rats ◽

Before And After

While most rats gain weight when placed on a high-fat diet (HFD), some strains resist HFD-induced weight gain. To maintain weight, obesity-resistant (OR) rats must either eat less than obesity-prone (OP) rats or increase total energy expenditure (TEE). To determine if changes in TEE predispose to or protect from weight gain, energy expenditure, energy intake, and weight gain were measured in male and female OP and OR rats consuming a low-fat diet (LFD) and for 5 days after switching to a HFD. After 5 days on a HFD, OP rats gained significantly more weight (male: 42.8 ± 6.9 g, female: 25.5 ± 3.0 g) than their OR counterparts (male: 24.0 ± 7.5 g, female: 13.7 ± 1.4 g). Both male and female rats significantly increased their energy intake when transitioned to the HFD, and TEE increased modestly in all groups. Compared with female OP rats, female OR rats had a significantly greater increase in TEE on the HFD. This was due to an increase in both resting and nonresting energy expenditure. In contrast, the effect of the HFD in males was minor. TEE was also measured in female rats consuming a HFD, pair fed to LFD calories. The increase in TEE of pair-fed female OR rats was substantially less than what was seen in the HFD ad libitum condition. Physical activity was also measured in female rats. There was no evidence that increases in physical activity were the cause of the increased TEE seen in female OR rats consuming a HFD. These results suggest that resistance to HFD-induced weight gain in female OR rats may be due in part to an increase in TEE and a greater reliance on lipid as an energy source. Changes in TEE appear to be triggered by overconsumption of the HFD and not simply the diet composition.

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