Maternal High-Fat Diet Multigenerationally Impairs Hippocampal Synaptic Plasticity and Memory in Male Rat Offspring

Endocrinology ◽  
2020 ◽  
Vol 162 (1) ◽  
Author(s):  
Cheng Lin ◽  
YanYan Lin ◽  
Ji Luo ◽  
JunRu Yu ◽  
YaNi Cheng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Learning And Memory ◽  
High Fat Diet ◽  
Maternal Diet ◽  
High Fat ◽  
Hippocampal Synaptic Plasticity ◽  
Insulin Replacement

Abstract As advances are made in the field of developmental origins of health and disease, there is an emphasis on long-term influence of maternal environmental factors on offspring health. Maternal high-fat diet (HFD) consumption has been suggested to exert detrimental effects on cognitive function in offspring, but whether HFD-dependent brain remodeling can be transmitted to the next generations is still unclear. This study tested the hypothesis that HFD consumption during rat pregnancy and lactation multigenerationally influences male offspring hippocampal synaptic plasticity and cognitive function. We observed that hippocampus-dependent learning and memory was impaired in 3 generations from HFD-fed maternal ancestors (referred as F1-F3), as assessed by novel object recognition and Morris water maze tests. Moreover, maternal HFD exposure also affected electrophysiological and ultrastructure measures of hippocampal synaptic plasticity across generations. We observed that intranasal insulin replacement partially rescued hippocampal synaptic plasticity and cognitive deficits in F3 rats, suggesting central insulin resistance may play an important role in maternal diet-induced neuroplasticity impairment. Furthermore, maternal HFD exposure enhanced the palmitoylation of GluA1 critically involved in long-term potentiation induction, while palmitoylation inhibitor 2-bromopalmitate counteracts GluA1 hyperpalmitoylation and partially abolishes the detrimental effects of maternal diet on learning and memory in F3 offspring. Importantly, maternal HFD-dependent GluA1 hyperpalmitoylation was reversed by insulin replacement. Taken together, our data suggest that maternal HFD exposure multigenerationally influences adult male offspring hippocampal synaptic plasticity and cognitive performance, and central insulin resistance may serve as the cross-talk between maternal diet and cognitive impairment across generations.

scholarly journals Maternal insulin resistance multigenerationally impairs synaptic plasticity and memory via gametic mechanisms

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Salvatore Fusco ◽  
Matteo Spinelli ◽  
Sara Cocco ◽  
Cristian Ripoli ◽  
Alessia Mastrodonato ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Synaptic Plasticity ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Brain Plasticity ◽  
Maternal Diet ◽  
Brain Health ◽  
High Fat ◽  
Bdnf Expression ◽  
Male Germline

Abstract Metabolic diseases harm brain health and cognitive functions, but whether maternal metabolic unbalance may affect brain plasticity of next generations is still unclear. Here, we demonstrate that maternal high fat diet (HFD)-dependent insulin resistance multigenerationally impairs synaptic plasticity, learning and memory. HFD downregulates BDNF and insulin signaling in maternal tissues and epigenetically inhibits BDNF expression in both germline and hippocampus of progeny. Notably, exposure of the HFD offspring to novel enriched environment restores Bdnf epigenetic activation in the male germline and counteracts the transmission of cognitive impairment to the next generations. BDNF administration to HFD-fed mothers or preserved insulin sensitivity in HFD-fed p66Shc KO mice also prevents the intergenerational transmission of brain damage to the progeny. Collectively, our data suggest that maternal diet multigenerationally impacts on descendants’ brain health via gametic mechanisms susceptible to lifestyle.

scholarly journals Does Long-Term High Fat Diet Always Lead to Smaller Hippocampi Volumes, Metabolite Concentrations, and Worse Learning and Memory? A Magnetic Resonance and Behavioral Study in Wistar Rats

PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0139987 ◽  
Author(s):  
Zuzanna Setkowicz ◽  
Agata Gaździńska ◽  
Joanna J. Osoba ◽  
Karolina Karwowska ◽  
Piotr Majka ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Learning And Memory ◽  
High Fat Diet ◽  
Wistar Rats ◽  
Behavioral Study ◽  
High Fat ◽  
Metabolite Concentrations

scholarly journals A long-term maternal diet intervention is necessary to avoid the obesogenic effect of maternal high-fat diet in the offspring

2018 ◽  
Vol 62 ◽  
pp. 210-220 ◽  
Author(s):  
Huiting Xu ◽  
Qiang Fu ◽  
Yi Zhou ◽  
Chengbin Xue ◽  
Patrick Olson ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Maternal Diet ◽  
High Fat ◽  
Diet Intervention

scholarly journals Long-Term Consumption of Platycodi Radix Ameliorates Obesity and Insulin Resistance via the Activation of AMPK Pathways

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Chae Eun Lee ◽  
Haeng Jeon Hur ◽  
Jin-Taek Hwang ◽  
Mi Jeong Sung ◽  
Hye Jeong Yang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Adipocyte Differentiation ◽  
Cultured Cells ◽  
C2c12 Myotubes ◽  
Obese Mice ◽  
High Fat ◽  
Platycodi Radix ◽  
Chemotactic Protein

This study was designed to evaluate the effects and mechanism of Platycodi radix, having white balloon flower (Platycodon grandiflorum for. albiflorum (Honda) H. Hara) on obesity and insulin resistance. The extracts of Platycodi radix with white balloon flower were tested in cultured cells and administered into mice on a high-fat diet. The Platycodi radix activated the AMPK/ACC phosphorylation in C2C12 myotubes and also suppressed adipocyte differentiation in 3T3-L1 cells. In experimental animal, it suppressed the weight gain of obese mice and ameliorated obesity-induced insulin resistance. It also reduced the elevated circulating mediators, including triglyceride (TG), T-CHO, leptin, resistin, and monocyte chemotactic protein (MCP)-1 in obesity. As shown in C2C12 myotubes, the administration of Platycodi radix extracts also recovered the AMPK/ACC phosphorylation in the muscle of obese mice. These results suggest that Platycodi radix with white balloon flower ameliorates obesity and insulin resistance in obese mice via the activation of AMPK/ACC pathways and reductions of adipocyte differentiation.

scholarly journals Necrostatin-1 Mitigates Cognitive Dysfunction in Prediabetic Rats With no Alteration in Insulin Sensitivity

2020 ◽  
Author(s):  
Ada Admin ◽  
Kewarin Jinawong ◽  
Nattayaporn Apaijai ◽  
Supawit Wongsuchai ◽  
Wasana Pratchayasakul ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Insulin Sensitivity ◽  
Cognitive Decline ◽  
High Fat Diet ◽  
Spine Density ◽  
High Fat ◽  
Dendritic Spine Density ◽  
Microglial Morphology ◽  
Brain Mitochondrial Function

Previous studies show that 12-week of high-fat diet (HFD) consumption caused not only prediabetes, but also cognitive decline and brain pathologies. Recently, necrostatin-1 (nec-1), a necroptosis inhibitor, showed beneficial effects in brain against stroke. However, the comparative effects of nec-1 and metformin on cognition and brain pathologies in prediabetes have not been investigated. We hypothesized that nec-1 and metformin equally attenuated cognitive decline and brain pathologies in prediabetic rats. Rats (n=32) were fed with either normal diet (ND) or high-fat diet (HFD) for 20 weeks. At week 13, ND-fed rats were given a vehicle (n=8) and HFD-fed rats were randomly assigned into 3 subgroups (n=8/subgroup) with vehicle, nec-1 or metformin for 8 weeks. Metabolic parameters, cognitive function, brain insulin receptor function, synaptic plasticity, dendritic spine density, microglial morphology, brain mitochondrial function, Alzheimer’s protein, and cell death were determined.<b> </b>HFD-fed rats exhibited prediabetes, cognitive decline, and brain pathologies. Nec-1 and metformin equally improved cognitive function, synaptic plasticity, dendritic spine density, microglial morphology, brain mitochondrial function, reduced hyperphosphorylated-tau and necroptosis in HFD-fed rats. Interestingly metformin, but not nec-1, improved brain insulin sensitivity in those rats.<b> </b><b> </b>In conclusion, necroptosis inhibition directly improved cognition in prediabetic rats without alteration in insulin sensitivity.

scholarly journals Comparative effects of sex hormone deprivation on the brain of insulin-resistant rats

2019 ◽  
Vol 241 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Jirapas Sripetchwandee ◽  
Hiranya Pintana ◽  
Piangkwan Sa-nguanmoo ◽  
Chiraphat Boonnag ◽  
Wasana Pratchayasakul ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Cognitive Decline ◽  
Mitochondrial Dysfunction ◽  
Dendritic Spine ◽  
High Fat Diet ◽  
High Fat ◽  
Long Term Depression ◽  
Impaired Insulin

Obese-insulin resistance following chronic high-fat diet consumption led to cognitive decline through several mechanisms. Moreover, sex hormone deprivation, including estrogen and testosterone, could be a causative factor in inducing cognitive decline. However, comparative studies on the effects of hormone deprivation on the brain are still lacking. Adult Wistar rats from both genders were operated upon (sham operations or orchiectomies/ovariectomies) and given a normal diet or high-fat diet for 4, 8 and 12 weeks. Blood was collected to determine the metabolic parameters. At the end of the experiments, rats were decapitated and their brains were collected to determine brain mitochondrial function, brain oxidative stress, hippocampal plasticity, insulin-induced long-term depression, dendritic spine density and cognition. We found that male and female rats fed a high-fat diet developed obese-insulin resistance by week 8 and brain defects via elevated brain oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression, hippocampal dysplasticity, reduced dendritic spine density and cognitive decline by week 12. In normal diet-fed rats, estrogen deprivation, not testosterone deprivation, induced obese-insulin resistance, oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression, hippocampal dysplasticity and reduced dendritic spine density. In high-fat–diet-fed rats, estrogen deprivation, not testosterone deprivation, accelerated and aggravated obese-insulin resistance and brain defects at week 8. In conclusion, estrogen deprivation aggravates brain dysfunction more than testosterone deprivation through increased oxidative stress, brain mitochondrial dysfunction, impaired insulin-induced long-term depression and dendritic spine reduction. These findings may explain clinical reports which show more severe cognitive decline in aging females than males with obese-insulin resistance.

scholarly journals Exercise Alleviates Cognitive Functions by Enhancing Hippocampal Insulin Signaling and Neuroplasticity in High-Fat Diet-Induced Obesity

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1603 ◽  
Author(s):  
Hye-Sang Park ◽  
Sang-Seo Park ◽  
Chang-Ju Kim ◽  
Mal-Soon Shin ◽  
Tae-Woon Kim
Keyword(s):  
Insulin Resistance ◽  
Cognitive Function ◽  
Physical Exercise ◽  
Dentate Gyrus ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Treadmill Exercise ◽  
High Fat ◽  
Brain Functions ◽  
Impaired Cognitive Function

Obesity, caused by a high-fat diet (HFD), leads to insulin resistance, which is a precursor of diabetes and a risk factor for impaired cognitive function, dementia, and brain diseases, such as Alzheimer’s disease. Physical exercise has positive effects on obesity and brain functions. We investigated whether the decline in cognitive function caused by a HFD could be improved through exercise by examining insulin signaling pathways and neuroplasticity in the hippocampus. Four-week-old C57BL/6 male mice were fed a HFD or a regular diet for 20 weeks, followed by 12 weeks of treadmill exercise. To ascertain the effects of treadmill exercise on impaired cognitive function caused by obesity, the present study implemented behavioral testing (Morris water maze, step-down). Moreover, insulin-signaling and neuroplasticity were measured in the hippocampus and dentate gyrus. Our results demonstrated that HFD-fed obesity-induced insulin resistance was improved by exercise. In addition, the HFD group showed a decrease in insulin signaling and neuroplasticity in the hippocampus and the dentate gyrus and increased cognitive function impairment, which were reversed by physical exercise. Overall, our findings indicate that physical exercise may act as a non-pharmacologic method that protects against cognitive dysfunction caused by obesity by improving hippocampal insulin signaling and neuroplasticity.

scholarly journals Oral supplementations with l-glutamine or l-alanyl-l-glutamine do not change metabolic alterations induced by long-term high-fat diet in the B6.129F2/J mouse model of insulin resistance

2015 ◽  
Vol 411 (1-2) ◽  
pp. 351-362 ◽  
Author(s):  
Patricia Martins Bock ◽  
Mauricio Krause ◽  
Helena Trevisan Schroeder ◽  
Gabriela Fernandes Hahn ◽  
Hilton Kenji Takahashi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mouse Model ◽  
High Fat Diet ◽  
High Fat ◽  
Metabolic Alterations
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