scholarly journals The Effects of Brain Serotonin Deficiency on Responses to High Fat Diet in Female Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Shama N. Huq ◽  
Allison K. Warner ◽  
Kerry Buckhaults ◽  
Benjamin D. Sachs
Keyword(s):  
High Fat Diet ◽  
Tryptophan Hydroxylase ◽  
Forced Swim Test ◽  
Brain Serotonin ◽  
Dependent Manner ◽  
Depression And Anxiety ◽  
High Fat ◽  
Anxiogenic Effect ◽  
Increased Risk ◽  
The Impact

Clinical studies have reported an increased risk of depression and anxiety disorders among individuals who are obese, and women are more likely than men to suffer from depression, anxiety, and obesity. However, the effects of obesity-promoting diets on depression- and anxiety-like behavior remain controversial. A recent study from our group used the tryptophan hydroxylase 2 (R439H) knock-in mouse line to evaluate the impact of genetic brain serotonin (5-HT) deficiency on behavioral responses to high fat diet (HFD) in male mice. That study indicated that chronic exposure to HFD induced pro-anxiety-like effects in the open field test and antidepressant-like effects in the forced swim test in wild-type males. Interestingly, the antidepressant-like effect of HFD, but not the anxiogenic effect, was blocked by brain 5-HT deficiency in males. The current work sought to repeat these studies in females. Our new data suggest that females are less susceptible than males to HFD-induced weight gain and HFD-induced alterations in behavior. In addition, the effects of chronic HFD on the expression of inflammation-related genes in the hippocampus were markedly different in females than we had previously reported in males, and HFD was shown to impact the expression of several inflammation-related genes in a genotype-dependent manner. Together, our findings highlight the importance of brain 5-HT and sex in regulating behavioral and molecular responses to HFD. Our results may have important implications for our understanding of the clinically observed sex differences in the consequences of obesity.

Abstract 655: Rac2 is a Key Modulator of IL-1β -dependent Atherosclerotic Plaque Calcification

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Nicolle Ceneri ◽  
Lina Zhao ◽  
Bryan D Young ◽  
Abigail L Healy ◽  
Suleyman Coskun ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
High Fat Diet ◽  
Cardiovascular Events ◽  
Stable Coronary Artery Disease ◽  
Plaque Burden ◽  
Mrna Levels ◽  
Dependent Manner ◽  
High Fat ◽  
Increased Risk ◽  
Calcified Plaque

The calcium composition of atherosclerotic plaque has predictive value for increased risk of cardiovascular events. Inflammation is associated with atherosclerotic calcification, but the immune signaling that regulates calcium mineralization in plaque is minimally understood. The hematopoietic Rac family member, Rac2, modulates the activation of immune cells and has potential to influence plaque osteogenesis. Both aortic plaque from ApoE -/- mice fed a high fat diet and coronary plaque from patients revealed increased Rac1:Rac2 expression ratios, driven by dynamic Rac2 expression, to be associated with calcified plaque. On high fat diet, Rac2 -/- ApoE -/- mice demonstrated comparable serum cholesterol and plaque burden relative to ApoE -/- mice, but histology identified differences in plaque structure and cellularity. MicroCT and calcium-targeted imaging identified increased atherosclerotic calcification, which was associated with elevated expression of osteogenic transcription factors and was dependent on the hematopoietic compartment. Calcified plaque expressed higher IL-1β mRNA levels, and serum revealed increased IL-1β protein concentrations. Rac2 -/- ApoE -/- macrophages demonstrated increased activation of Rac1 and consequent Rac1-dependent IL-1β secretion. Downstream of Rac1, NF-κB and reactive oxygen species (ROS) signaling drove IL-1β production by increasing IL-1β mRNA expression and caspase1 activation. Cultured mouse aorta smooth muscle cells mineralized calcium in an IL-1β dose-dependent manner, and the enhanced atherosclerotic calcification in vivo was inhibited by IL-1 receptor antagonist, confirming a cause-and-effect relationship. In patients with stable coronary artery disease, high coronary calcium burden was associated with increased serum IL-1β, and patients with combined elevations in calcium and IL-1β had more events driven by higher mortality, reinforcing the relevance of this inflammatory calcification signaling axis to human disease. Therapeutic targeting of IL-1β expression through the balance of Rac activation has potential to impact patient care by modulating atherosclerotic calcification and consequent cardiovascular events.

Chronic high-fat diet increases acute neuroendocrine stress response independently of prenatal dexamethasone treatment in male rats

2013 ◽  
Vol 26 (1) ◽  
pp. 8-18 ◽  
Author(s):  
Anders Abildgaard ◽  
Sten Lund ◽  
Karin S Hougaard
Keyword(s):  
Stress Response ◽  
Hpa Axis ◽  
High Fat Diet ◽  
Forced Swim Test ◽  
Male Rats ◽  
Adolescent Male ◽  
Late Adolescent ◽  
High Fat ◽  
Obesity And Diabetes ◽  
Increased Risk

ObjectiveIntrauterine growth restriction (IUGR) has been associated with metabolic disorders later in life such as obesity and diabetes as well as psychiatric disorders such as depression and schizophrenia. Therefore, we wanted to investigate whether behavioural, metabolic or neuroendocrine abnormalities could be provoked or exacerbated by a high-fat diet (HFD) in an experimental model of IUGR.MethodsPregnant dams were exposed to dexamethasone (DEX) in the third gestational week to induce IUGR. Late adolescent male offspring of DEX- and vehicle-treated dams were then fed a HFD or standard chow for 8 weeks and subjected to a variety of assessments.ResultsOnly diet affected the hypothalamus-pituitary-adrenal (HPA) axis stress response, as HFD doubled the observed corticosterone levels following acute restraint. HFD and prenatal DEX exposure concomitantly exacerbated depressive-like behaviour in the forced swim test, even though no interaction was seen. Prenatal DEX treatment tended to increase the basal acoustic startle response (ASR), while an interaction between HFD and DEX was present in the ASR pre-pulse inhibition suggestive of fundamental changes in neuronal gating mechanisms. Metabolic parameters were only affected by diet, as HFD increased fasting glucose and insulin levels.ConclusionWe conclude that chronic HFD may be more important in programming of the HPA axis stress responsiveness than an adverse foetal environment and therefore potentially implies an increased risk for developing psychiatric and metabolic disease.

scholarly journals 12-Hydroxyeicosapentaenoic acid inhibits foam cell formation and ameliorates high-fat diet-induced pathology of atherosclerosis in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takahiro Nagatake ◽  
Yuki Shibata ◽  
Sakiko Morimoto ◽  
Eri Node ◽  
Kento Sawane ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Foam Cell ◽  
Linseed Oil ◽  
Cell Formation ◽  
Chronic Inflammatory Disease ◽  
Foam Cell Formation ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
High Fat ◽  
The Impact

AbstractAtherosclerosis is a chronic inflammatory disease associated with macrophage aggregate and transformation into foam cells. In this study, we sought to investigate the impact of dietary intake of ω3 fatty acid on the development of atherosclerosis, and demonstrate the mechanism of action by identifying anti-inflammatory lipid metabolite. Mice were exposed to a high-fat diet (HFD) supplemented with either conventional soybean oil or α-linolenic acid-rich linseed oil. We found that as mice became obese they also showed increased pulsatility and resistive indexes in the common carotid artery. In sharp contrast, the addition of linseed oil to the HFD improved pulsatility and resistive indexes without affecting weight gain. Histological analysis revealed that dietary linseed oil inhibited foam cell formation in the aortic valve. Lipidomic analysis demonstrated a particularly marked increase in the eicosapentaenoic acid-derived metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) in the serum from mice fed with linseed oil. When we gave 12-HEPE to mice with HFD, the pulsatility and resistive indexes was improved. Indeed, 12-HEPE inhibited the foamy transformation of macrophages in a peroxisome proliferator-activated receptor (PPAR)γ-dependent manner. These results demonstrate that the 12-HEPE-PPARγ axis ameliorates the pathogenesis of atherosclerosis by inhibiting foam cell formation.

scholarly journals The Impact of Maternal High-Fat Diet on Bone Microarchitecture in Offspring

2021 ◽  
Vol 8 ◽  
Author(s):  
Emma J. Buckels ◽  
Scott M. Bolam ◽  
Mei Lin Tay ◽  
Brya G. Matthews
Keyword(s):  
Bone Health ◽  
High Fat Diet ◽  
Maternal Obesity ◽  
Bone Microarchitecture ◽  
Later Life ◽  
Reproductive Age ◽  
High Fat ◽  
Increased Risk ◽  
Increase Fracture Risk ◽  
The Impact

The incidence of obesity in women of reproductive age has significantly increased over the past 100 years. There is a well-established connection between maternal obesity during pregnancy and an increased risk of developing non-communicable cardiometabolic diseases in her offspring. This mini-review focuses on evidence examining the effect of maternal high-fat diet (HFD) on skeletal development and bone health in later life in offspring. The majority of rodent studies indicate that maternal HFD generally negatively affects both embryonic bone development and bone volume in adult animals. Details surrounding the mechanisms of action that drive changes in the skeleton in offspring remain unclear, although numerous studies suggest that some effects are sex-specific. Human studies in this area are limited but also suggest that HFD during pregnancy may impair bone formation and increase fracture risk during childhood. Given the consequences of low bone mass and deranged bone microarchitecture for offspring, advances in our understanding of the developmental origins of bone health is critical in the battle against osteoporosis.

scholarly journals High fat diet exacerbates cognitive decline in mouse models of Alzheimer's disease and mixed dementia in a sex-dependent manner.

2021 ◽  
Author(s):  
Olivia Jane Gannon ◽  
Lisa Suzanne Robison ◽  
Abigail E Salinero ◽  
Charly Abi-Ghanem ◽  
Febronia Morcos Mansour ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Mouse Models ◽  
High Fat Diet ◽  
Cerebral Hypoperfusion ◽  
Dependent Manner ◽  
Mixed Dementia ◽  
High Fat ◽  
The Impact

Approximately 70% of Alzheimer's disease (AD) patients have co-morbid vascular contributions to cognitive impairment and dementia (VCID); this highly prevalent overlap of dementia subtypes is known as mixed dementia (MxD). AD is more prevalent in women, while VCID is slightly more prevalent in men. Sex differences in risk factors may contribute to sex differences in dementia subtypes. Unlike metabolically healthy women, diabetic women are more likely to develop VCID than diabetic men. Prediabetes is 3x more prevalent than diabetes and is linked to earlier onset of dementia in women, but not men. How prediabetes influences underlying pathology and cognitive outcomes across different dementia subtypes is unknown. To fill this gap in knowledge, we investigated the impact of diet-induced prediabetes and biological sex on cognitive function and neuropathology in mouse models of AD and MxD. Male and female 3xTg-AD mice received a sham (AD model) or unilateral common carotid artery occlusion surgery to induce chronic cerebral hypoperfusion (MxD model). Mice were fed a control or high fat (HF; 60% fat) diet for 3 months prior to behavior assessment. In both sexes, HF diet elicited a prediabetic phenotype (impaired glucose tolerance) and weight gain. In females, but not males, metabolic consequences of a HF diet were more severe in AD or MxD mice compared to WT. In both sexes, HF-fed AD or MxD mice displayed deficits in spatial memory in the Morris water maze (MWM). In females, but not males, HF-fed AD and MxD mice also displayed impaired spatial learning in the MWM. In females, but not males, AD or MxD caused deficits in activities of daily living, regardless of diet. Astrogliosis was more severe in AD and MxD females compared to males. Further, HF diet caused greater accumulation of amyloid beta in MxD females compared to MxD males. In females, but not males, more severe glucose intolerance (prediabetes) was correlated with increased hippocampal microgliosis. In conclusion, high fat diet had a wider array of metabolic, cognitive, and neuropathological consequences in AD and MxD females compared to males. These findings shed light on potential underlying mechanisms by which prediabetes may lead to earlier dementia onset in women.

scholarly journals High-Fat Diet Alters LH Secretion and Pulse Frequency in Female Mice in an Estrous Cycle-Dependent Manner

Endocrinology ◽  
2020 ◽  
Vol 161 (10) ◽  
Author(s):  
Ariel L Negrón ◽  
Sally Radovick
Keyword(s):  
Estrous Cycle ◽  
High Fat Diet ◽  
Hormone Replacement ◽  
Pulse Frequency ◽  
Chow Diet ◽  
Dependent Manner ◽  
High Fat ◽  
Pulsatile Release ◽  
The Impact ◽  
Estradiol Levels

Abstract Reproductive fitness in females is susceptible to obesogenic diets. Energy balance and reproduction are tightly regulated, in part, by hypothalamic neurons in the arcuate nucleus (ARC), and high-fat diet (HFD) can steadily increase estradiol levels in rodents. Estradiol regulates the reproductive axis via negative feedback mechanisms in ARC neurons by modulating pulsatile release of the gonadotropin luteinizing hormone (LH). However, it is unclear how the circulating estradiol milieu of adult females interacts with a state of high-caloric fat intake to alter LH pulse dynamics. Here, we used serial tail-tip blood sampling to measure pulsatile LH release at different estrous cycle stages in mice fed a HFD. Starting at 21 days of age, female C57BL/6J mice were freely fed with either regular chow diet (RD) or 60% kcal HFD for 12 weeks. Blood samples were collected once at diestrus, and then again at estrus. LH was measured in 10-minute intervals for 3 hours and analyzed for pulse frequency, amplitude, and mean and basal LH levels. Compared with RD-fed controls, mice fed HFD displayed significantly increased pulse frequency at diestrus, but not at estrus. HFD-fed mice also had lower mean and basal LH levels compared with RD-fed controls, but only during estrus. These data suggest that circulating estradiol can variably contribute to the impact that HFD has on LH pulsatile release and also provide insight into how obesity impacts women’s reproductive health when ovarian estradiol levels drastically change, such as during menopause or with hormone replacement therapy.

scholarly journals High-fat diet and estrogen impacts the colon and its transcriptome in a sex-dependent manner

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
L. Hases ◽  
A. Archer ◽  
R. Indukuri ◽  
M. Birgersson ◽  
C. Savva ◽  
...  
Keyword(s):  
Sex Differences ◽  
High Fat Diet ◽  
Clock Genes ◽  
Control Diet ◽  
Macrophage Infiltration ◽  
Dependent Manner ◽  
High Fat ◽  
Selective Activation ◽  
The Metabolic Syndrome ◽  
The Impact

Abstract There is a strong association between obesity and colorectal cancer (CRC), especially in men, whereas estrogen protects against both the metabolic syndrome and CRC. Colon is the first organ to respond to high-fat diet (HFD), and estrogen receptor beta (ERβ) can attenuate CRC development. How estrogen impacts the colon under HFD and related sex differences has, however, not been investigated. To dissect this, mice were fed control diet or HFD for 13 weeks and administered receptor-selective estrogenic ligands for the last three weeks. We recorded impact on metabolism, colon crypt proliferation, macrophage infiltration, and the colon transcriptome. We found clear sex differences in the colon transcriptome and in the impact by HFD and estrogens, including on clock genes. ERα-selective activation reduced body weight and generated systemic effects, whereas ERβ-selective activation had local effects in the colon, attenuating HFD-induced macrophage infiltration and epithelial cell proliferation. We here demonstrate how HFD and estrogens modulate the colon microenvironment in a sex- and ER-specific manner.

scholarly journals Chronic spinal cord changes in a high-fat diet-fed male rat model of thoracic spinal contusion

2017 ◽  
Vol 49 (9) ◽  
pp. 519-529 ◽  
Author(s):  
Redin A. Spann ◽  
William J. Lawson ◽  
Raymond J. Grill ◽  
Michael R. Garrett ◽  
Bernadette E. Grayson
Keyword(s):  
Metabolic Disease ◽  
Spinal Cord ◽  
High Fat Diet ◽  
Immune Cell ◽  
Male Rat ◽  
High Fat ◽  
Thoracic Spinal ◽  
Increased Risk ◽  
Cord Injury ◽  
The Impact

Individuals that suffer injury to the spinal cord can result in long-term, debilitating sequelae. Spinal cord-injured patients have increased risk for the development of metabolic disease, which can further hinder the effectiveness of treatments to rehabilitate the cord and improve quality of life. In the present study, we sought to understand the impact of high-fat diet (HFD)-induced obesity on spinal cord injury (SCI) by examining transcriptome changes in the area of the injury and rostral and caudal to site of damage 12 wk after injury. Adult, male Long-Evans rats received either thoracic level contusion of the spinal cord or sham laminectomy and then were allowed to recover on normal rat chow for 4 wk and further on HFD for an additional 8 wk. Spinal cord tissues harvested from the rats were processed for Affymetrix microarray and further transcriptomic analysis. Diverse changes in gene expression were identified in the injured cord in genes such as MMP12, APOC4, GPNMB, and IGF1 and 2. The greatest signaling changes occurred in pathways involved in cholesterol biosynthesis and immune cell trafficking. Together, the cord changes in the chronically obese rat following thoracic SCI reveal further potential targets for therapy. These could be further explored as they overlap with genes involved in metabolic disease.

scholarly journals The Impact of Obesity and Consumption of a High Fat Diet on Anxiety-Like Behavior in Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1239-1239 ◽  
Author(s):  
Shelby Van Leuven ◽  
Amanda Carey ◽  
Laura Squiccimara ◽  
Guilia Pintea
Keyword(s):  
Open Field ◽  
High Fat Diet ◽  
Undergraduate Research ◽  
Forced Swim Test ◽  
Control Diet ◽  
Stress Hormone ◽  
High Fat ◽  
Swim Test ◽  
Forced Swim ◽  
The Impact

Abstract Objectives This study sought to measure the behavioral effects of consumption of a high-fat diet (HFD) on anxiety-like and depression-like behaviors in mice. It is hypothesized that animals consuming a HFD would exhibit more anxiety-like and depressive-like behaviors than their counterparts consuming a control diet. Methods Thirty C57BL6 mice were separated into two groups (n = 15/each) and placed on either a HFD (60% from fat) or control diet (CD) (10% from fat) for four months prior to behavioral testing. Anxiogenic behavior was assessed by three behavioral measures: (1) marble burying, during which the number of marbles buried in bedding was recorded as an index of compulsive behavior, (2) light-dark exploration, in which time spent in the brightly-lit chamber was considered an index of anti-anxiety-like behavior and (3) the open field test, in which time spent in the brightly-lit center of the field was recorded as an index of anti-anxiety-like behavior. Depression-like behavior was assessed using the forced swim test, during which immobility was measured as an index of behavioral despair. Furthermore, the stress hormone corticosterone and the cytokine interleukin-6 (IL-6) were measured (in urine and cortex, respectively). Results The mice fed HFD demonstrated more anxiety-like behaviors than the CD mice. The HFD-fed mice spent significantly less time in the brightly-lit chamber in light-dark exploration test and significantly less time in the center of the open field compared to the CD mice. The number of marbles buried was significantly correlated with weight and locomotor activity and thus, could not be attributed to anxiety. Analysis of the forced swim test did not reveal any significant differences in the time spent immobile or latency to immobility between the two diet groups. Urinary analysis of corticosterone levels showed greater levels of the stress hormone in the HFD-fed mice. There was also a significant increase in IL-6 in the cortex of the mice fed HFD. Conclusions These data demonstrated that HFDs increased anxiety-like, but not depressive-like behaviors in mice. This anxiogenic behavior was associated with increased stress hormone and inflammation, however, further research is needed to determine if this association is also observed in humans. Funding Sources Summer Undergraduate Research Program at Simmons (SURPASs).

scholarly journals High fat diet worsens pathology and impairment in an Alzheimer’s mouse model, but not by synergistically decreasing cerebral blood flow

2019 ◽  
Author(s):  
Oliver Bracko ◽  
Lindsay K. Vinarcsik ◽  
Jean C. Cruz Hernández ◽  
Nancy E. Ruiz-Uribe ◽  
Mohammad Haft-Javaherian ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
High Fat Diet ◽  
Brain Inflammation ◽  
Neutrophil Adhesion ◽  
High Fat ◽  
Increased Risk ◽  
The Impact

AbstractObesity is linked to increased risk for and severity of Alzheimer’s disease (AD). Cerebral blood flow (CBF) reductions are an early feature of AD and are also linked to obesity. We showed that non-flowing capillaries, caused by adhered neutrophils, underlie the CBF reduction in mouse models of AD. Because obesity could exacerbate the vascular inflammation likely underlying this neutrophil adhesion, we tested links between obesity and AD by feeding APP/PS1 mice a high fat diet (Hfd) and evaluating behavioral, physiological, and pathological changes. We found trends toward poorer memory performance in APP/PS1 mice fed a Hfd, impaired social interactions with either APP/PS1 genotype or a Hfd, and synergistic impairment of sensory-motor function in APP/PS1 mice fed a Hfd. The Hfd led to increases in amyloid-beta monomers and plaques in APP/PS1 mice, as well as increased brain inflammation. These results agree with previous reports showing obesity exacerbates AD-related pathology and symptoms in mice. We used a crowd-sourced, citizen science approach to analyze imaging data to determine the impact of the APP/PS1 genotype and a Hfd capillary stalling and CBF. Surprisingly, we did not see an increase in the number of non-flowing capillaries or a worsening of the CBF deficit in APP/PS1 mice fed a Hfd as compared to controls, suggesting capillary stalling is not a mechanistic link between a Hfd and increased severity of AD in mice. Reducing capillary stalling by blocking neutrophil adhesion improved CBF and short-term memory function in APP/PS1 mice, even when fed a Hfd.Significance statementObesity, especially in mid-life, has been linked to increased risk for and severity of Alzheimer’s disease. Here, we show that blocking adhesion of white blood cells leads to increases in brain blood flow that improve cognitive function, regardless of whether mice are obese or not.

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