scholarly journals Role of sex and high fat diet in metabolic and hypothalamic disturbances in the 3xTg-AD mouse model of Alzheimer’s disease

2020 ◽  
Author(s):  
Lisa. S. Robison ◽  
Olivia J. Gannon ◽  
Melissa A. Thomas ◽  
Abigail E. Salinero ◽  
Charly Abi-Ghanem ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Mouse Model ◽  
Glucose Intolerance ◽  
Systemic Inflammation ◽  
Fat Mass ◽  
High Fat Diet ◽  
Control Diet ◽  
High Fat ◽  
Increased Risk ◽  
Ad Mouse Model

AbstractHypothalamic dysfunction occurs early in the clinical course of Alzheimer’s disease (AD), likely contributing to disturbances in feeding behavior and metabolic function that are often observable years prior to the onset of cognitive symptoms. Late-life weight loss and low BMI are associated with increased risk of dementia and faster progression of disease. However, high fat diet and metabolic disease (e.g. obesity, type 2 diabetes), particularly in mid-life, are associated with increased risk of AD, as well as exacerbated AD pathology and behavioral deficits in animal models. In the current study, we explored possible relationships between hypothalamic function, diet/metabolic status, and AD. Considering the sex bias in AD, with women representing two-thirds of AD patients, we sought to determine whether these relationships vary by sex. WT and 3xTg-AD male and female mice were fed a control (10% fat) or high fat (HF; 60% diet) diet from ~3-7 months of age, then tested for metabolic and hypothalamic disturbances. On control diet, male 3xTg-AD mice displayed decreased body weight, reduced fat mass, hypoleptinemia, and mild systemic inflammation, as well as increased expression of gliosis- and inflammation-related genes in the hypothalamus (Iba1, GFAP, TNF-α, IL-1β). In contrast, female 3xTg-AD mice on control diet displayed metabolic disturbances opposite that of 3xTg-AD males (increased body and fat mass, impaired glucose tolerance). HF diet resulted in expected metabolic alterations across groups (increased body and fat mass; glucose intolerance; increased plasma insulin and leptin, decreased ghrelin; nonalcoholic fatty liver disease-related pathology). HF diet resulted in the greatest weight gain, adiposity, and glucose intolerance in 3xTg-AD females, which were associated with markedly increased hypothalamic expression of GFAP and IL-1β, as well as GFAP labeling in several hypothalamic nuclei that regulate energy balance. In contrast, HF diet increased diabetes markers and systemic inflammation preferentially in AD males but did not exacerbate hypothalamic inflammation in this group. These findings provide further evidence for the roles of hypothalamic and metabolic dysfunction in AD, which in the 3xTg-AD mouse model appears to be dependent on both sex and diet.

scholarly journals Role of sex and high-fat diet in metabolic and hypothalamic disturbances in the 3xTg-AD mouse model of Alzheimer’s disease

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Lisa S. Robison ◽  
Olivia J. Gannon ◽  
Melissa A. Thomas ◽  
Abigail E. Salinero ◽  
Charly Abi-Ghanem ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Mouse Model ◽  
Glucose Intolerance ◽  
Systemic Inflammation ◽  
Fat Mass ◽  
High Fat Diet ◽  
Control Diet ◽  
High Fat ◽  
Increased Risk ◽  
Ad Mouse Model

Abstract Background Hypothalamic dysfunction occurs early in the clinical course of Alzheimer’s disease (AD), likely contributing to disturbances in feeding behavior and metabolic function that are often observed years prior to the onset of cognitive symptoms. Late-life weight loss and low BMI are associated with increased risk of dementia and faster progression of disease. However, high-fat diet and metabolic disease (e.g., obesity, type 2 diabetes), particularly in mid-life, are associated with increased risk of AD, as well as exacerbated AD pathology and behavioral deficits in animal models. In the current study, we explored possible relationships between hypothalamic function, diet/metabolic status, and AD. Considering the sex bias in AD, with women representing two-thirds of AD patients, we sought to determine whether these relationships vary by sex. Methods WT and 3xTg-AD male and female mice were fed a control (10% fat) or high-fat (HF 60% fat) diet from ~ 3–7 months of age, then tested for metabolic and hypothalamic disturbances. Results On control diet, male 3xTg-AD mice displayed decreased body weight, reduced fat mass, hypoleptinemia, and mild systemic inflammation, as well as increased expression of gliosis- and inflammation-related genes in the hypothalamus (Iba1, GFAP, TNF-α, IL-1β). In contrast, female 3xTg-AD mice on control diet displayed metabolic disturbances opposite that of 3xTg-AD males (increased body and fat mass, impaired glucose tolerance). HF diet resulted in expected metabolic alterations across groups (increased body and fat mass; glucose intolerance; increased plasma insulin and leptin, decreased ghrelin; nonalcoholic fatty liver disease-related pathology). HF diet resulted in the greatest weight gain, adiposity, and glucose intolerance in 3xTg-AD females, which were associated with markedly increased hypothalamic expression of GFAP and IL-1β, as well as GFAP labeling in several hypothalamic nuclei that regulate energy balance. In contrast, HF diet increased diabetes markers and systemic inflammation preferentially in AD males but did not exacerbate hypothalamic inflammation in this group. Conclusions These findings provide further evidence for the roles of hypothalamic and metabolic dysfunction in AD, which in the 3xTg-AD mouse model appears to be dependent on both sex and diet.

Sex differences in response to a high fat diet in an Alzheimer’s Disease mouse model

2018 ◽  
Author(s):  
Alejandra Freire Fernández-Regatillo ◽  
María L. de Ceballos ◽  
Jesús Argente ◽  
Sonia Díaz Pacheco ◽  
Clara González Martínez
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Mouse Model ◽  
High Fat Diet ◽  
High Fat

scholarly journals High-Fat Diet Changes Fungal Microbiomes and Interkingdom Relationships in the Murine Gut

mSphere ◽  
2017 ◽  
Vol 2 (5) ◽  
Author(s):  
Timothy Heisel ◽  
Emmanuel Montassier ◽  
Abigail Johnson ◽  
Gabriel Al-Ghalith ◽  
Yi-Wei Lin ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Bacterial Community ◽  
Mouse Model ◽  
High Fat Diet ◽  
Developed Countries ◽  
Potential Contribution ◽  
High Fat ◽  
Functional Relationships ◽  
Increased Risk ◽  
Bacterial Microbiome

ABSTRACT Recent research shows that gut microbes are involved in the development of obesity, a growing health problem in developed countries that is linked to increased risk for cardiovascular disease. However, studies showing links between microbes and metabolism have been limited to the analysis of bacteria and have ignored the potential contribution of fungi in metabolic health. This study provides evidence that ingestion of a high-fat diet is associated with changes to the fungal (and bacterial) microbiome in a mouse model. In addition, we find that interkingdom structural and functional relationships exist between fungi and bacteria within the gut and that these are perturbed by high-fat diet. Dietary fat intake and shifts in gut bacterial community composition are associated with the development of obesity. To date, characterization of microbiota in lean versus obese subjects has been dominated by studies of gut bacteria. Fungi, recently shown to affect gut inflammation, have received little study for their role in obesity. We sought to determine the effects of high-fat diet on fungal and bacterial community structures in a mouse model using the internal transcribed spacer region 2 (ITS2) of fungal ribosomal DNA (rDNA) and the 16S rRNA genes of bacteria. Mice fed a high-fat diet had significantly different abundances of 19 bacterial and 6 fungal taxa than did mice fed standard chow, with high-fat diet causing similar magnitudes of change in overall fungal and bacterial microbiome structures. We observed strong and complex diet-specific coabundance relationships between intra- and interkingdom microbial pairs and dramatic reductions in the number of coabundance correlations in mice fed a high-fat diet compared to those fed standard chow. Furthermore, predicted microbiome functional modules related to metabolism were significantly less abundant in high-fat-diet-fed than in standard-chow-fed mice. These results suggest a role for fungi and interkingdom interactions in the association between gut microbiomes and obesity. IMPORTANCE Recent research shows that gut microbes are involved in the development of obesity, a growing health problem in developed countries that is linked to increased risk for cardiovascular disease. However, studies showing links between microbes and metabolism have been limited to the analysis of bacteria and have ignored the potential contribution of fungi in metabolic health. This study provides evidence that ingestion of a high-fat diet is associated with changes to the fungal (and bacterial) microbiome in a mouse model. In addition, we find that interkingdom structural and functional relationships exist between fungi and bacteria within the gut and that these are perturbed by high-fat diet.

Sign in / Sign up

Export Citation Format

Share Document