Maternal high-fat diet in mice induces cerebrovascular, microglial and long-term behavioural alterations in offspring

AbstractVarious environmental exposures during pregnancy, like maternal diet, can compromise, at critical periods of development, the neurovascular maturation of the offspring. Foetal exposure to maternal high-fat diet (mHFD), common to Western societies, has been shown to disturb neurovascular development in neonates and long-term permeability of the neurovasculature. Nevertheless, the effects of mHFD on the offspring’s cerebrovascular health remains largely elusive. Here, we sought to address this knowledge gap by using a translational mouse model of mHFD exposure. Three-dimensional and ultrastructure analysis of the neurovascular unit (vasculature and parenchymal cells) in mHFD-exposed offspring revealed major alterations of the neurovascular organization and metabolism. These alterations were accompanied by changes in the expression of genes involved in metabolism and immunity, indicating that neurovascular changes may result from abnormal brain metabolism and immune regulation. In addition, mHFD-exposed offspring showed persisting behavioural alterations reminiscent of neurodevelopmental disorders, specifically an increase in stereotyped and repetitive behaviours into adulthood.

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

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2018.09.008 ◽

2018 ◽

Vol 62 ◽

pp. 210-220 ◽

Cited By ~ 6

Author(s):

Huiting Xu ◽

Qiang Fu ◽

Yi Zhou ◽

Chengbin Xue ◽

Patrick Olson ◽

...

Keyword(s):

High Fat Diet ◽

Maternal Diet ◽

High Fat ◽

Diet Intervention

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A long-term maternal diet transition from high-fat diet to normal fat diet during pre-pregnancy avoids adipose tissue inflammation in next generation

PLoS ONE ◽

10.1371/journal.pone.0209053 ◽

2018 ◽

Vol 13 (12) ◽

pp. e0209053 ◽

Cited By ~ 2

Author(s):

Michelle Summerfield ◽

Yi Zhou ◽

Tianhao Zhou ◽

Chaodong Wu ◽

Gianfranco Alpini ◽

...

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Maternal Diet ◽

Adipose Tissue Inflammation ◽

Next Generation ◽

High Fat ◽

Tissue Inflammation

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

Endocrinology ◽

10.1210/endocr/bqaa214 ◽

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.

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The beneficial effects of Lactobacillus fermented black barley on high fat diet-induced fatty liver in rats

Food & Function ◽

10.1039/d1fo00290b ◽

2021 ◽

Author(s):

Qi Guan ◽

Xinwen Ding ◽

Lingyue Zhong ◽

Chuang Zhu ◽

Pan Nie ◽

...

Keyword(s):

Fatty Liver ◽

High Fat Diet ◽

Metabolic Disorders ◽

High Fat ◽

Beneficial Effects ◽

Phytochemical Composition

Long term high-fat diet (HF) can cause metabolic disorders, which might induce fatty liver. Fermented whole cereal food exhibit healthy potential due to their unique phytochemical composition and probiotics. In...

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Telmisartan prevents high-fat diet-induced neurovascular impairments and reduces anxiety-like behavior

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x211003497 ◽

2021 ◽

pp. 0271678X2110034

Author(s):

Gianna Huber ◽

Mikolaj Ogrodnik ◽

Jan Wenzel ◽

Ines Stölting ◽

Lukas Huber ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

High Fat Diet ◽

Neurovascular Unit ◽

Laser Speckle ◽

Angiotensin Ii Receptor ◽

High Fat ◽

Diet Induced Obesity ◽

Whisker Pad ◽

Receptor Blockers

Angiotensin II receptor blockers (telmisartan) prevent rodents from diet-induced obesity and improve their metabolic status. Hyperglycemia and obesity are associated with reduced cerebral blood flow and neurovascular uncoupling which may lead to behavioral deficits. We wanted to know whether a treatment with telmisartan prevents these changes in obesity. We put young mice on high-fat diet and simultaneously treated them with telmisartan. At the end of treatment, we performed laser speckle imaging and magnetic resonance imaging to assess the effect on neurovascular coupling and cerebral blood flow. Different behavioral tests were used to investigate cognitive function. Mice developed diet-induced obesity and after 16, not 8 weeks of high-fat diet, however, the response to whisker pad stimulation was about 30% lower in obese compared to lean mice. Simultaneous telmisartan treatment increased the response again by 10% compared to obese mice. Moreover, telmisartan treatment normalized high-fat diet-induced reduction of cerebral blood flow and prevented a diet-induced anxiety-like behavior. In addition to that, telmisartan affects cellular senescence and string vessel formation in obesity. We conclude, that telmisartan protects against neurovascular unit impairments in a diet-induced obesity setting and may play a role in preventing obesity related cognitive deficits in Alzheimer’s disease.

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A Newly Developed Synbiotic Yogurt Prevents Diabetes by Improving the Microbiome–Intestine–Pancreas Axis

International Journal of Molecular Sciences ◽

10.3390/ijms22041647 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1647

Author(s):

Brandi Miller ◽

Rabina Mainali ◽

Ravinder Nagpal ◽

Hariom Yadav

Keyword(s):

High Fat Diet ◽

Microbiota Composition ◽

Preventive Strategies ◽

Human Origin ◽

High Fat ◽

Diabetes In Mice ◽

Diabetes Progression ◽

Gut Microbiota Composition

The prevalence of type 2 diabetes mellitus (T2D) is increasing worldwide, and there are no long-term preventive strategies to stop this growth. Emerging research shows that perturbations in the gut microbiome significantly contribute to the development of T2D, while microbiome modulators may be beneficial for T2D prevention. However, microbiome modulators that are effective, safe, affordable, and able to be administered daily are not yet available. Based on our previous pro- and prebiotic studies, we developed a novel synbiotic yogurt comprised of human-origin probiotics and plant-based prebiotics and investigated its impact on diet- and streptozotocin-induced T2D in mice. We compared the effects of our synbiotic yogurt to those of a commercially available yogurt (control yogurt). Interestingly, we found that the feeding of the synbiotic yogurt significantly reduced the development of hyperglycemia (diabetes) in response to high-fat diet feeding and streptozotocin compared to milk-fed controls. Surprisingly, the control yogurt exacerbated diabetes progression. Synbiotic yogurt beneficially modulated the gut microbiota composition compared to milk, while the control yogurt negatively modulated it by significantly increasing the abundance of detrimental bacteria such as Proteobacteria and Enterobacteriaceae. In addition, the synbiotic yogurt protected pancreatic islet morphology compared to the milk control, while the control yogurt demonstrated worse effects on islets. These results suggest that our newly developed synbiotic yogurt protects against diabetes in mice and can be used as a therapeutic to prevent diabetes progression.

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Long-term High Fat Diet Consumption Reversibly Alters Feeding Behavior via a Dopamine-Associated Mechanism in Mice

Behavioural Brain Research ◽

10.1016/j.bbr.2021.113470 ◽

2021 ◽

pp. 113470

Author(s):

Everett Altherr ◽

Aundrea Rainwater ◽

Darian Kaviani ◽

Qijun Tang ◽

Ali D. Güler

Keyword(s):

Feeding Behavior ◽

High Fat Diet ◽

High Fat

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High Fat Diet Mediates Amyloid-β Cleaving Enzyme 1 Phosphorylation and SUMOylation, Enhancing Cognitive Impairment in APP/PS1 Mice

Journal of Alzheimer s Disease ◽

10.3233/jad-215299 ◽

2021 ◽

pp. 1-14

Author(s):

Jian Bao ◽

Zheng Liang ◽

Xiaokang Gong ◽

Jing Yu ◽

Yifan Xiao ◽

...

Keyword(s):

Cognitive Performance ◽

High Fat Diet ◽

Amyloid Β ◽

Normal Diet ◽

Standard Diet ◽

High Fat ◽

Augmented Learning ◽

Biochemical Analyses ◽

Modifiable Lifestyle Factors

Background: Alzheimer’s disease (AD) is the most common form of dementia in older adults and extracellular accumulation of amyloid-β (Aβ) is one of the two characterized pathologies of AD. Obesity is significantly associated with AD developing factors. Several studies have reported that high fat diet (HFD) influenced Aβ accumulation and cognitive performance during AD pathology. However, the underlying neurobiological mechanisms have not yet been elucidated. Objective: The objective of this study was to explore the underlying neurobiological mechanisms of HFD influenced Aβ accumulation and cognitive performance during AD pathology. Methods: 2.5-month-old male APP/PS1 mice were randomly separated into two groups: 1) the normal diet (ND) group, fed a standard diet (10 kcal%fat); and 2) the HFD group, fed a high fat diet (40 kcal%fat, D12492; Research Diets). After 4 months of HFD or ND feeding, mice in the two groups were subjected for further ethological, morphological, and biochemical analyses. Results: A long-term HFD diet significantly increased perirenal fat and impaired dendritic integrity and aggravated neurodegeneration, and augmented learning and memory deficits in APP/PS1 mice. Furthermore, the HFD increased beta amyloid cleaving enzyme 1 (BACE1) dephosphorylation and SUMOylation, resulting in enhanced enzyme activity and stability, which exacerbated the deposition of amyloid plaques. Conclusion: Our study demonstrates that long-term HFD consumption aggravates amyloid-β accumulation and cognitive impairments, and that modifiable lifestyle factors, such as obesity, can induce BACE1 post-modifications which may contribute to AD pathogenesis.

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