scholarly journals Maternal and offspring high-fat diet leads to platelet hyperactivation in male mice offspring

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Renato S. Gaspar ◽  
Amanda J. Unsworth ◽  
Alaa Al-Dibouni ◽  
Alexander P. Bye ◽  
Tanya Sage ◽  
...  

AbstractMaternal over-nutrition increases the risk of diabetes and cardiovascular events in offspring. While prominent effects on cardiovascular health are observed, the impact on platelet physiology has not been studied. Here, we examined whether maternal high-fat diet (HF) ingestion affects the platelet function in lean and obese offspring. C57BL6/N mice dams were given a HF or control (C) diet for 8 weeks before and during pregnancy. Male and female offspring received C or HF diets for 26 weeks. Experimental groups were: C/C, dam and offspring fed standard laboratory diet; C/HF dam fed standard laboratory diet and offspring fed HF diet; HF/C and HF/HF. Phenotypic and metabolic tests were performed and blood collected for platelet studies. Compared to C/C, offspring HF groups were obese, with fat accumulation, hyperglycaemia and insulin resistance. Female offspring did not present platelet hyperactivity, hence we focused on male offspring. Platelets from HF/HF mice were larger, hyperactive and presented oxidative stress when compared to C/C. Maternal and offspring HF diet results in platelet hyperactivation in male mouse offspring, suggesting a novel ‘double-hit’ effect.

Metabolism ◽  
2021 ◽  
Vol 116 ◽  
pp. 154635
Author(s):  
Gustavo Venâncio da Silva ◽  
Marina Galleazzo Martins ◽  
Giovana Pereira de Oliveira ◽  
Alessandra Gonçalves Cruz ◽  
Larissa Pereira Rodrigues ◽  
...  

2018 ◽  
Vol 315 (6) ◽  
pp. H1713-H1723 ◽  
Author(s):  
Lia E. Taylor ◽  
Ellen E. Gillis ◽  
Jacqueline B. Musall ◽  
Babak Baban ◽  
Jennifer C. Sullivan

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.


Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2493
Author(s):  
Maria Nunez-Salces ◽  
Hui Li ◽  
Stewart Christie ◽  
Amanda J. Page

The stomach is the primary source of the orexigenic and adiposity-promoting hormone, ghrelin. There is emerging evidence on the nutrient-mediated modulation of gastric ghrelin secretion. However, limited information is available on gastric nutrient-sensing mechanisms in high-fat diet (HFD)-induced obesity. This study investigated the impact of HFD-induced obesity on the expression of nutrient chemosensors in mouse stomach, particularly ghrelin cells. Male C57BL/6 mice were fed either a standard laboratory diet (SLD) or HFD for 12 weeks. The expression of ghrelin, enzymes involved in ghrelin production (PC1/3, GOAT) and nutrient chemosensors (CD36, FFAR2&4, GPR93, CaSR, mGluR4 and T1R3) was determined by quantitative RT-PCR in the mouse corpus and antrum. Immunohistochemistry assessed the protein expression of CaSR and ghrelin in the corpus and antrum. Antral mRNA levels of CaSR and PC1/3 were increased in HFD compared to SLD mice, while mRNA levels of all other nutrient chemosensors examined remained unchanged. CaSR immunolabelling was observed in the gastric antrum only. Nearly 80% of antral ghrelin cells expressed CaSR, with a similar cell density and co-expression in SLD and HFD mice. In conclusion, HFD-induced obesity increased CaSR mRNA expression in mouse antrum. However, the high antral co-expression of CaSR and ghrelin was unaltered in HFD compared to SLD mice.


2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Weston He ◽  
Trupti Trivedi ◽  
Gabriel Pagnotti ◽  
Sreemala Murthy ◽  
Yun She ◽  
...  

Background and Hypothesis: Hyperglycemia is a major source of disease and morbidity among the adult population. Prior studies correlate long-term high fat diet (HFD) mediated hyperglycemia with bone fragility and muscle weakness. Furthermore, the mechanism driving hyperglycemia between sexes are unknown. Our group previously showed that HFDs induced insulin resistance in male mice and glucose intolerance in female mice. This establishes the need to study the impact of long-term HFDs on the bones and muscles using an older cohort of both male and female mice. For that, we hypothesized a long-term HFD mediated hyperglycemia will change bone and muscle structures and impair their functions in adult male and female mice. Experimental Design or Project Methods: 22-week C57Bl6 mice were fed either a HFD or low fat diet (LFD) for 25 weeks. After euthanasia, bones and muscles were harvested and evaluated using MicroCT, histology, and mechanical testing. Statistical analysis was performed using GraphPad Prism with p<0.05 considered significant. Results: MicoCT data saw significant reductions to cortical thickness (p<0.05), bone mineral density (p<0.001), and increases to medullary area (p<0.05) among HFD males and females compared to LFD. HFD-males also experienced significant increase in cortical porosity (P<0.001) whereas no changes were noted in HFDfemales. Trabecular bone volume was relatively unchanged. HFD increased cortical osteoclast surface (p<0.001) for both sexes. Bone histology saw increased marrow adiposity among HFD-females (p<0.05). Muscle histology exhibited HFD-related reductions in myofiber diameter (p<0.001) for both sexes. Mechanical testing demonstrated reduced young’s modulus (p<0.05) and yield stress (p<0.05) among HFD mice, despite non-significant differences in ultimate strength. Conclusion and Potential Impact: The changes associated with a long-term HFD differed between sexes but still led to functional impairments of bone and muscle for both sexes, emphasizing the importance of looking further into the mechanisms responsible for these changes. This can potentially translate to the clinic in the treatment of musculoskeletal complications associated with HFDs.


2021 ◽  
Vol 8 ◽  
Author(s):  
Scott M. Bolam ◽  
Vidit V. Satokar ◽  
Subhajit Konar ◽  
Brendan Coleman ◽  
Andrew Paul Monk ◽  
...  

Background: Over half of women of reproductive age are now overweight or obese. The impact of maternal high-fat diet (HFD) is emerging as an important factor in the development and health of musculoskeletal tissues in offspring, however there is a paucity of evidence examining its effects on tendon. Alterations in the early life environment during critical periods of tendon growth therefore have the potential to influence tendon health that cross the lifespan. We hypothesised that a maternal HFD would alter biomechanical, morphological and gene expression profiles of adult offspring rotator cuff tendon.Materials and Methods: Female Sprague-Dawley rats were randomly assigned to either: control diet (CD; 10% kcal or 43 mg/g from fat) or HFD (45% kcal or 235 mg/g from fat) 14 days prior to mating and throughout pregnancy and lactation. Eight female and male offspring from each maternal diet group were weaned onto a standard chow diet and then culled at postnatal day 100 for tissue collection. Supraspinatus tendons were used for mechanical testing and histological assessment (cellularity, fibre organisation, nuclei shape) and tail tendons were collected for gene expression analysis.Results: A maternal HFD increased the elasticity (Young's Modulus) in the supraspinatus tendon of male offspring. Female offspring tendon biomechanical properties were not affected by maternal HFD. Gene expression of SCX and COL1A1 were reduced in male and female offspring of maternal HFD, respectively. Despite this, tendon histological organisation were similar between maternal diet groups in both sexes.Conclusion: An obesogenic diet during pregnancy increased tendon elasticity in male, but not female, offspring. This is the first study to demonstrate that maternal diet can modulate the biomechanical properties of offspring tendon. A maternal HFD may be an important factor in regulating adult offspring tendon homeostasis that may predispose offspring to developing tendinopathies and adverse tendon outcomes in later life.


Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 1149-P
Author(s):  
ADJOA OSEI-NTANSAH ◽  
TRINITEE R. OLIVER ◽  
CLAIRE FALZARANO ◽  
TAYLOR LOFTON ◽  
STANLEY ANDRISSE

2020 ◽  
Author(s):  
Renato Simões Gaspar ◽  
Amanda J Unsworth ◽  
Alex Bye ◽  
Tanya Sage ◽  
Michelle Stewart ◽  
...  

Abstract Background: Maternal over-nutrition increases the risk of diabetes and cardiovascular events in offspring. While prominent effects on cardiovascular health are observed, the impact of this on platelet physiology has not been studied. Here, we sought to determine whether maternal high-fat diet (HF) ingestion can affect the platelet function in offspring.Methods: C57BL6/N mice dams were given a HF or control (C) diet for 8 weeks prior to and during pregnancy. Male offspring also received either C or HF diets for 26 weeks. Experimental groups were: C/C, dam and offspring fed chow; C/HF dam fed chow and offspring fed high-fat diet; HF/C and HF/HF. Various phenotypic (including body weight and % of body fat) and metabolic (glycaemia, triglyceridemia) tests were performed and blood collected for platelet studies. Results: Compared to C/C, HF/HF animals were obese, with fat accumulation, hyperglycaemia, insulin resistance and low respiratory exchange rate. HF/HF, but not C/HF mice also showed hypertriglyceredaemia and higher mean platelet volume. These platelets were hyperreactive, displaying higher fibrinogen binding after stimulation with different agonists. They also showed increased platelet adhesion and spreading on collagen. Maternal obesity led to an overall effect of increased platelet reactivity in offspring. Both maternal and offspring HF groups presented decreased levels of collagen receptor GPVI with increased oxidative stress. Western blotting experiments in stimulated platelets showed increased phosphorylation of PKC substrates, total tyrosine and AKT at Ser473, whilst response to nitric oxide donor PAPA-NONOate was unchanged compared to C/C.Conclusions: Maternal HF diet ingestion programmes platelet hyperactivation in male mouse offspring, whilst HF in both dams and offspring resulted in a 'double-hit' effect of increased serum triglyceride levels, large platelets and increased reactivity. This involved enhanced Tyr phosphorylation, ROS production and decreased GPVI expression. Since platelet function can be programmed by early developmental periods, it is possible to use this window of intervention to reduce the risk of thrombotic events.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Lenka Žaloudková ◽  
Alena Tichá ◽  
Jana Nekvindová ◽  
Ladislava Pavlíková ◽  
Zdeněk Zadák ◽  
...  

The aim of this study was to determine the effect of natural and encapsulated sources of ursolic acid on liver regeneration. Four ursolate sources were tested. Two forms of ursolic acid encapsulates were combined with cyclodextrins, i.e., gamma-CD (gCD) and beta-CD, and two natural sources were adjusted by homogenization (HAP) and micronization of apple peel using Jonagold apples. All ursolate forms were applied intragastrically in daily doses of 20 mg for 7 days. Laboratory rats were fed with standard laboratory diet. Further, gCD and MAP were also tested with a high-fat diet (6 weeks). Partial hepatectomy (PH) was performed 24 hours before the end of the experiment. The concentration of plasma hepatocyte growth factor (HGF) was determined with an immunoassay; simultaneously, the expression of HGF and CYP7A1 in the liver was quantified through qPCR. HGF expression and plasma levels were significantly increased 24 hours after PH in both the HAP (p=0.038) and HFgCD groups (p=0.036), respectively. The correlation between HGF expression and plasma values was significant (p=0.04). The positive effects on liver regeneration were found in both the gCD and HAP forms of ursolic acid, whose effects were confirmed through the upregulation of HGF.


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