scholarly journals High-fat diet induces autonomic dysfunction, cardiac remodeling and metabolic changes in ovariectomized ApoE-Ko mices

Author(s):  
João Eduardo Izaias ◽  
Bruno Nascimento-Carvalho ◽  
Thália Leticia Brito Nascimento ◽  
Thayná Fabiana Ribeiro Batista ◽  
Bruno Durante da Silva ◽  
...  

Abstract Atherosclerosis is a chronic inflammatory disease characterized by the formation of atheroma plaque in the arterial wall, process that causes long-term obstruction of the arteries. Postmenopausal women tend to have greater body adiposity, factor that corroborate to increased risk of cardiovascular events and development of atherosclerosis. Therefore, the aim of this study was to evaluate the association of experimental model of atherosclerosis with ovarian deprivation and consumption of high-fat diet in metabolic, hemodynamic, and autonomic outcomes. 21 female ApoE-Ko were divided into 3 groups (n = 7 in each): control treated with normolipidic diet (C); ovariectomized treated with normolipidic diet (Ovx); ovariectomized treated with high-fat diet (OvxHF). Hemodynamic parameters, baroreflex sensitivity and cardiovascular autonomic modulation were evaluated. Values (mean ± standard error of mean) were analyzed by One-way ANOVA, followed by Tukey's post hoc (p<0.05). The OvxHF showed increase in final body weight, adipose tissue, tachycardia at rest, in addition, there was a decrease in muscle mass, functional capacity, baroreflex sensitivity associated with less cardiac autonomic modulation. These findings provide evidence about the risk by the loss of ovarian hormones with food consumption and demonstrate the importance of adhering to prevention and treatment strategies.

1994 ◽  
Vol 71 (06) ◽  
pp. 755-758 ◽  
Author(s):  
E M Bladbjerg ◽  
P Marckmann ◽  
B Sandström ◽  
J Jespersen

SummaryPreliminary observations have suggested that non-fasting factor VII coagulant activity (FVII:C) may be related to the dietary fat content. To confirm this, we performed a randomised cross-over study. Seventeen young volunteers were served 2 controlled isoenergetic diets differing in fat content (20% or 50% of energy). The 2 diets were served on 2 consecutive days. Blood samples were collected at 8.00 h, 16.30 h and 19.30 h, and analysed for triglycerides, FVII coagulant activity using human (FVII:C) or bovine thromboplastin (FVII:Bt), and FVII amidolytic activity (FVIPAm). The ratio FVII:Bt/FVII:Am (a measure of FVII activation) increased from fasting levels on both diets, but most markedly on the high-fat diet. In contrast, FVII: Am (a measure of FVII protein) tended to decrease from fasting levels on both diets. FVII:C rose from fasting levels on the high-fat diet, but not on the low-fat diet. The findings suggest that high-fat diets increase non-fasting FVII:C, and consequently may be associated with increased risk of thrombosis.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Yumiko Oishi ◽  
Ichiro Manabe ◽  
Kazuyuki Tobe ◽  
Takashi Kadowaki ◽  
Ryozo Nagai

We have previously shown that a zinc finger transcription factor, Krüppel-like factor 5 (KLF5), plays an important role in pathogenesis of cardiovascular diseases, such as atherosclerosis. KLF5 heterozygous knockout ( KLF5 +/ − ) mice exhibited much less neointima formation, cardiac hypertrophy and fibrosis. We also found that expression of KLF5 correlated with a higher incidence of restenosis following PCI and the SNP located within the KLF5 promoter was associated with an increased risk of hypertension in man. Interestingly, KLF5 is also expressed in metabolic tissues such as adipose tissue, skeletal muscle, and pancreatic β-cells. Thus, we hypothesized that KLF5 might play a role in metabolic diseases. To test this, KLF5 +/ − mice were fed with high-fat diet. Although KLF5 +/ − mice ate more food than wild-type littermates, they were resistant to high-fat diet-induced obesity and protected from dyslipidemia, glucose intolerance and hepatic steatosis, indicating that KLF5 + /− mice were less susceptible to metabolic syndrome. The systemic O 2 consumption and expression of genes involved in energy expenditure in skeletal muscle were increased in KLF5 + /− mice, demonstrating enhanced energy expenditure, which partly explains the phenotype. Knocking down KLF5 by siRNA increased expression levels of UCP2/3 and CPT-1b in C2C12 myotubes, suggesting that KLF5 may inhibit energy expenditure-related genes. Chromatin immunoprecipitation and coimmunoprecipitation assays showed that KLF5 interacted with corepressors, such as SMRT and NCoR, and strongly inhibited the UCP and CPT-1b promoters. We found that this inhibitory activity of KLF5 depended on its SUMOylation. When KLF5 was deSUMOylated, it activated the promoters. These data demonstrate that KLF5 acts as a molecular switch for energy expenditure and the posttranslational modifications of KLF5 including SUMOylation turns on/off the switch function of KLF5. Given that KLF5 also controls tissue remodeling in response to external stress, KLF5 may mediate metabolic dysfunction and atherosclerosis in metabolic syndrome. Our findings also suggest that the posttranscriptional modification of KLF5 is an attractive novel therapeutic target.


Author(s):  
Kinga Gawlińska ◽  
Dawid Gawliński ◽  
Małgorzata Filip ◽  
Edmund Przegaliński

Abstract A balanced maternal diet is essential for proper fetal development, and the consumption of a nutritionally inadequate diet during intrauterine development and early childhood is associated with a significantly increased risk of metabolic and brain disorders in offspring. The current literature indicates that maternal exposure to a high-fat diet exerts an irreversible influence on the general health of the offspring. This review of preclinical research examines the relationship between a maternal high-fat diet during pregnancy or lactation and metabolic changes, molecular alterations in the brain, and behavioral disorders in offspring. Animal models indicate that offspring exposed to a maternal high-fat diet during pregnancy and lactation manifest increased depressive-like and aggressive behaviors, reduced cognitive development, and symptoms of metabolic syndrome. Recently, epigenetic and molecular studies have shown that maternal nutrition during pregnancy and the suckling period modifies the development of neurotransmitter circuits and many other factors important to central nervous system development. This finding confirms the importance of a balanced maternal diet for the health of offspring.


2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
JuRyoun Soh ◽  
Dae Young Kwon ◽  
Youn-Soo Cha

We found that Chongkukjang, traditional unsalted fermented soybean, has an antiobesity effect in mice with diet-induced obesity and examined the changes in hepatic transcriptional profiles using cDNA microarray. High-fat diet-induced obese C57BL/6J mice were divided into three groups: normal-diet control group (NDcon, 10% of total energy from fat), high-fat diet control group (HDcon, 45% of total energy from fat), and HDcon plus 40% Chongkukjang (HDC) and were fed for 9 weeks. The HDC group mice were pair-fed (isocalorie) with mice in the HDcon group. Final body weight, epididymal fat accumulation, serum total cholesterol, and LDL-cholesterol were improved in HDC group. The cDNA microarray analyses revealed marked alterations in the expression of about 800 genes. Several genes involved in fatty acid catabolism (Acaa2, Mgll, Phyh, Slc27a2, and Slc27a5) were normalized by Chongkukjang consumption. This study showed beneficial effects of Chongkukjang consumption in preventing diet-induced obesity and related metabolic abnormalities.


mSphere ◽  
2017 ◽  
Vol 2 (5) ◽  
Author(s):  
Timothy Heisel ◽  
Emmanuel Montassier ◽  
Abigail Johnson ◽  
Gabriel Al-Ghalith ◽  
Yi-Wei Lin ◽  
...  

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.


2020 ◽  
Author(s):  
Lisa. S. Robison ◽  
Olivia J. Gannon ◽  
Melissa A. Thomas ◽  
Abigail E. Salinero ◽  
Charly Abi-Ghanem ◽  
...  

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.


2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Ana Laura de Souza Campiello Talarico ◽  
Barbara Bim Simões ◽  
Caroline Altenburg Rozza ◽  
Fernanda Brognara-Dias ◽  
Daniel Penteado Martins Dias

2020 ◽  
Author(s):  
Christine Müller ◽  
Laura M. Zidek ◽  
Sabrina Eichwald ◽  
Cornelis F. Calkhoven

AbstractChronic obesity is correlated with severe metabolic and cardiovascular diseases as well as with an increased risk for developing cancers. Obesity is usually characterized by fat accumulation in enlarged - hypertrophic – adipocytes that are a source of inflammatory mediators, which is seen as causal for developing metabolic disorders. Yet, in certain healthy obese individuals fat is stored in metabolically more favorable hyperplastic fat tissue that contains an increased number of smaller adipocytes that are less inflamed. In a previous study we demonstrated that C/EBPβ-LIP deficient, yet C/EBPβ-LAP proficient mice show an expanded health and lifespan. Here we show that in mice on a high-fat diet LIP-deficiency results in adipocyte hyperplasia as well as efficient fat storage in subcutaneous depots associated with metabolic and inflammatory improvements. Our data identify C/EBPβ as a regulator of adipocyte fate in response to increased fat intake, which has major implications for metabolic health and aging.


2009 ◽  
Vol 21 (9) ◽  
pp. 84
Author(s):  
K. Chiam ◽  
S. Jindal ◽  
N. Ryan ◽  
S. Moretta ◽  
M. De Blasio ◽  
...  

The World Health Organization has stated that 75% of adults worldwide are overweight, and in Australia nearly 25% of men are obese. Obesity is associated with an increased risk of cardiovascular disease, type 2 diabetes and cancer, with 30 to 40% of the latter possibly preventable by maintaining a healthy weight (The International Association for the Study of Obesity). Prostate cancer is the most commonly diagnosed cancer in men and there is increasing evidence that obesity increases the risk of prostate cancer mortality. High birth weight, an indication of excess nutrition during foetal development, has been associated with an increased risk of childhood and adult obesity, and for cancer. Using an animal model, we investigated whether obese mothers are more likely to have obese sons who are at an increased risk of developing prostate abnormalities and thus prostate cancer, in adulthood. Female rats were fed with either a control diet (4g fat/kg) or high fat diet (100g fat/kg) from before mating and throughout pregnancy. Prostate tissues were collected from the male offspring at 90 days (post-puberty) and 180 days (young adult). Histological analysis of the day 90 prostates identified hyperplasia in 100% of the ventral lobes (VL) and 64% of the dorsolateral lobes (DLP) in offspring of the maternal high fat group compared to 0% in each respectively, in those of the maternal control diet group. The VL is the most hormone sensitive prostate lobe of the rat, while the DLP is considered the equivalent of the human peripheral zone, the region from which the majority of human prostate cancers arise. These results suggest for the first time that maternal high fat diet may induce prostate abnormalities in male offspring that may in turn, predispose to an increased risk of prostate cancer in later life.


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