166. MATERNAL OBESITY IS ASSOCIATED WITH AN INCREASED INCIDENCE OF PROSTATE ABNORMALITIES IN ADULT RAT OFFSPRING

2009 ◽  
Vol 21 (9) ◽  
pp. 84
Author(s):  
K. Chiam ◽  
S. Jindal ◽  
N. Ryan ◽  
S. Moretta ◽  
M. De Blasio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Fat Diet ◽  
Control Diet ◽  
Male Offspring ◽  
Female Rats ◽  
World Health ◽  
High Birth Weight ◽  
Healthy Weight ◽  
High Fat ◽  
Increased Risk

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.

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 Macrophage Inhibitory Cytokine-1 Induced by a High-Fat Diet Promotes Prostate Cancer Progression by Stimulating Tumor Promoting Cytokine Production from Tumor Stromal Cells

2020 ◽  
Author(s):  
Mingguo Huang ◽  
Shintaro Narita ◽  
Atsushi Koizumi ◽  
Taketoshi Nara ◽  
Kazuyuki Numakura ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
High Fat Diet ◽  
Control Diet ◽  
High Body Mass Index ◽  
High Serum ◽  
High Fat ◽  
Stromal Fibroblasts ◽  
Stromal Microenvironment

Abstract Background: Recent studies have indicated that a high-fat diet (HFD) and/or HFD-induced obesity may influence prostate cancer (PCa) progression, but the role of HFD in PCa microenvironment is unclear. Methods: In this study, we investigated the role of HFD on PCa stromal microenvironment using the PC-3M-luc-C6 PCa model mice fed with HFD or control diet, especially focusing on macrophage inhibitory cytokine-1 (MIC-1) and its effect on the tumor microenvironment. In addition, the synergistic effect of periprostatic adipocytes (PPAC), derived from primary PCa patients, on activation and cytokine secretion of prostate stromal fibroblasts were investigated. The expression pattern and role of MIC-1 signaling on human PCa stroma activation and PCa progression were investigated.Results: The HFD consumption stimulated PCa cell growth and invasion as a result of upregulated MIC-1 signaling and subsequent increased secretion of interleukin (IL)-8 and IL-6 from prostate stromal fibroblasts in the PC-3M-luc-C6 PCa model mice. In addition, PPAC directly stimulated MIC-1 production from PC-3 cells and IL-8 secretion in prostate stromal fibroblasts through upregulation of the adipolysis and free fatty acid (FFA) release. The increased serum MIC-1 was significantly correlated with human PCa stroma activation, high serum IL-8, IL-6 and lipase activity, advanced PCa progression, and high body mass index of the patients. Glial-derived neurotrophic factor receptor alpha-like (GFRAL), a specific receptor of MIC-1, was highly expressed in both the cytoplasm and membrane of the PCa cells and the surrounding stromal fibroblasts, and the expression level was decreased by androgen deprivation therapy and chemotherapy. Conclusion: HFD-mediated activation of the PCa stromal microenvironment through metabolically upregulated MIC-1 signaling by increased available free fatty acids may be a critical mechanism of HFD and/or obesity induced PCa progression.

scholarly journals High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
David P. Labbé ◽  
Giorgia Zadra ◽  
Meng Yang ◽  
Jaime M. Reyes ◽  
Charles Y. Lin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
High Fat Diet ◽  
Cellular Proliferation ◽  
Saturated Fat ◽  
Prostate Cancer Progression ◽  
Transcriptional Program ◽  
High Fat ◽  
Metabolic Alterations ◽  
Increased Risk

Abstract Systemic metabolic alterations associated with increased consumption of saturated fat and obesity are linked with increased risk of prostate cancer progression and mortality, but the molecular underpinnings of this association are poorly understood. Here, we demonstrate in a murine prostate cancer model, that high-fat diet (HFD) enhances the MYC transcriptional program through metabolic alterations that favour histone H4K20 hypomethylation at the promoter regions of MYC regulated genes, leading to increased cellular proliferation and tumour burden. Saturated fat intake (SFI) is also associated with an enhanced MYC transcriptional signature in prostate cancer patients. The SFI-induced MYC signature independently predicts prostate cancer progression and death. Finally, switching from a high-fat to a low-fat diet, attenuates the MYC transcriptional program in mice. Our findings suggest that in primary prostate cancer, dietary SFI contributes to tumour progression by mimicking MYC over expression, setting the stage for therapeutic approaches involving changes to the diet.

scholarly journals Perinatal exposure to a high-fat diet alters proopiomelanocortin, neuropeptide Y and dopaminergic receptors gene expression and the food preference in offspring adult rats

2022 ◽  
Vol 82 ◽  
Author(s):  
L. S. Santos ◽  
R. J. B. Matos ◽  
G. S. Cordeiro ◽  
G. S. Perez ◽  
D. A. E. Santo ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Food Preference ◽  
Control Diet ◽  
Female Rats ◽  
Dopaminergic Receptors ◽  
High Fat ◽  
Adult Rats ◽  
Genes Expression ◽  
Pregnancy And Lactation

Abstract Exposure to the hight-fat diet may alter the control of food intake promoting hyperphagia and obesity. The objective of this study was to investigate the effects of this diet on dopamine receptors (drd1 and drd2), proopiomelanocortin (pomc), neuropeptideY (npy) genes expression, and preference food in adult rats. Wistar female rats were fed a hight-fat or control diet during pregnancy and lactation. The offspring were allocated into groups: Lactation – Control (C) and High-fat (H). Post-weaning – Control Control (CC), offspring of mothers C, fed a control diet after weaning; Control Hight-fat (CH), offspring of mothers C, fed a hight-fat diet after weaning; Hight-fat Control (HC), offspring of mothers H, fed with control diet after weaning; and Hight-fat Hight-fat (HH), offspring of mothers H, fed a H diet after weaning. The groups CH and HH presented greater expression of drd1 in comparison to the CC. The drd2 of CH and HC presented higher gene expression than did CC. HH presented higher pomc expression in comparison to the other groups. HC also presented greater expression in comparison to CH. The npy of HH presented greater expression in relation to CH and HC. HH and HC have had a higher preference for a high-fat diet at 102º life’s day. The high-fat diet altered the gene expression of the drd1, drd2, pomc and npy, and influencing the food preference for high-fat diet.

scholarly journals Effects of obesity and exercise on colon cancer induction and hematopoiesis in mice

2019 ◽  
Vol 316 (2) ◽  
pp. E210-E220 ◽  
Author(s):  
Russell Emmons ◽  
Guanying Xu ◽  
Diego Hernández-Saavedra ◽  
Adam Kriska ◽  
Yuan-Xiang Pan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Fat Diet ◽  
Control Diet ◽  
High Fat ◽  
Preneoplastic Lesions ◽  
Hematopoietic Stem ◽  
Colon Inflammation ◽  
Increased Risk ◽  
Myeloid Progenitor Cells

Obesity-induced inflammation is associated with increased risk for colorectal cancer (CRC). The role of diet and exercise in modulating increased CRC risk in obesity and the potential role of altered hematopoiesis as a contributor to these effects remain unknown. The purpose of this study was to examine how weight loss induced during CRC induction with or without exercise alters CRC initiation and its relationship to altered hematopoiesis. Mice consumed either a control (CON) or a high-fat diet to induce obesity. All mice were then placed on the control diet during CRC induction with azoxymethane (AOM). Following AOM injection, mice originally on the high-fat diet were randomized into sedentary (HF-SED) or exercise trained (HF-EX) conditions. At euthanasia, body weight and fat mass were similar among all three groups ( P < 0.05). Compared with CON and HF-EX, HF-SED developed increased content of preneoplastic lesions ( P < 0.05), and HF-SED had significantly increased markers of colon inflammation compared with CON. Compared with both CON and HF-EX, HF-SED had decreased content of short-term hematopoietic stem cells and increased content of common myeloid progenitor cells (both P < 0.05). Similarly, HF-SED had increased bone marrow adiposity compared with CON and HF-EX ( P < 0.05), and proteomics analysis revealed an increased marker of bone marrow inflammation in HF-SED compared with CON and HF-EX. Our results suggest that the early removal of a high-fat diet reduces CRC incidence when combined with an exercise training intervention. This reduction in risk was related to lower colon inflammation with anti-inflammatory changes in hematopoiesis induced by exercise.

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.

scholarly journals Prenatal exposure to a maternal low-protein diet programmes a preference for high-fat foods in the young adult rat

2004 ◽  
Vol 92 (3) ◽  
pp. 513-520 ◽  
Author(s):  
Leanne Bellinger ◽  
Christina Lilley ◽  
Simon C. Langley-Evans
Keyword(s):  
Feeding Behaviour ◽  
Control Diet ◽  
Food Selection ◽  
Male Offspring ◽  
Female Rats ◽  
High Fat ◽  
Control Female ◽  
High Carbohydrate ◽  
Low Protein ◽  
Significant Difference

Nutrient restriction in pregnancy has been shown to programme adult obesity. Modulation of feeding behaviour may provide a mechanism through which obesity may be programmed. Pregnant Wistar rats were fed either a control diet or a low-protein (LP) diet throughout gestation. Their offspring were allocated to a self-selected-diet protocol to assess appetite and food preferences at 12 and at 30 weeks of age. Self-selection of high-fat, high-protein or high-carbohydrate foods by 12-week-old rats indicated that the prenatal environment influenced feeding behaviour. Both male and female offspring of LP-fed mothers consumed significantly more of the high-fat (P>0·001) and significantly less (P>0·02) of the high-carbohydrate food than the control animals. Female, but not male, offspring of LP-fed rats failed to adjust food intake to maintain a constant energy intake and had higher fat (P>0·005) and energy intakes (P>0·05) than control female rats. At 30 weeks of age there were no differences in the pattern of food selection between the two groups of animals. Male offspring of LP-fed rats had significantly more gonadal fat than control animals (P>0·05), but analysis of total body fat content indicated that there was no significant difference in overall adiposity. The present study suggests that in young adults at least, early life exposure to undernutrition determines a preference for fatty foods. Maternal nutrition may thus promote changes in systems that are involved in control of appetite or the perception of palatability.

Non-Fasting Factor VII Coagulant Activity (FVII:C) Increased by High-Fat Diet

1994 ◽  
Vol 71 (06) ◽  
pp. 755-758 ◽  
Author(s):  
E M Bladbjerg ◽  
P Marckmann ◽  
B Sandström ◽  
J Jespersen
Keyword(s):  
High Fat Diet ◽  
Fat Content ◽  
Factor Vii ◽  
Amidolytic Activity ◽  
High Fat ◽  
Low Fat Diet ◽  
Increased Risk ◽  
Coagulant Activity ◽  
High Fat Diets ◽  
Fat Diets

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.

scholarly journals Methionine restriction plus overload improves skeletal muscle and metabolic health in old mice on a high fat diet

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anandini Swaminathan ◽  
Andrej Fokin ◽  
Tomas Venckūnas ◽  
Hans Degens
Keyword(s):  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Muscle Mass ◽  
Body Mass ◽  
High Fat Diet ◽  
Control Diet ◽  
Metabolic Health ◽  
High Fat ◽  
Methionine Restriction ◽  
Old Mice

AbstractMethionine restriction (MR) has been shown to reduce the age-induced inflammation. We examined the effect of MR (0.17% methionine, 10% kCal fat) and MR + high fat diet (HFD) (0.17% methionine, 45% kCal fat) on body mass, food intake, glucose tolerance, resting energy expenditure, hind limb muscle mass, denervation-induced atrophy and overload-induced hypertrophy in young and old mice. In old mice, MR and MR + HFD induced a decrease in body mass. Muscle mass per body mass was lower in old compared to young mice. MR restored some of the HFD-induced reduction in muscle oxidative capacity. The denervation-induced atrophy of the m. gastrocnemius was larger in animals on MR than on a control diet, irrespective of age. Old mice on MR had larger hypertrophy of m. plantaris. Irrespective of age, MR and MR + HFD had better glucose tolerance compared to the other groups. Young and old mice on MR + HFD had a higher resting VO2 per body mass than HFD group. Mice on MR and MR + HFD had a resting respiratory quotient closer to 0.70, irrespective of age, indicating an increased utilization of lipids. In conclusion, MR in combination with resistance training may improve skeletal muscle and metabolic health in old age even in the face of obesity.

scholarly journals Perinatal High-Fat Diet Influences Ozone-Induced Responses on Pulmonary Oxidant Status and the Molecular Control of Mito-Phagy in Female Rat Offspring

2021 ◽  
Vol 22 (14) ◽  
pp. 7551
Author(s):  
Sven H. Rouschop ◽  
Samantha J. Snow ◽  
Urmila P. Kodavanti ◽  
Marie-José Drittij ◽  
Lou M. Maas ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
High Fat Diet ◽  
Control Diet ◽  
Ozone Exposure ◽  
Female Rat ◽  
Induced Responses ◽  
High Fat ◽  
Molecular Control ◽  
Rat Offspring ◽  
Oxidant Status

Previous research has shown that a perinatal obesogenic, high-fat diet (HFD) is able to exacerbate ozone-induced adverse effects on lung function, injury, and inflammation in offspring, and it has been suggested that mitochondrial dysfunction is implicated herein. The aim of this study was to investigate whether a perinatal obesogenic HFD affects ozone-induced changes in offspring pulmonary oxidant status and the molecular control of mitochondrial function. For this purpose, female Long-Evans rats were fed a control diet or HFD before and during gestation, and during lactation, after which the offspring were acutely exposed to filtered air or ozone at a young-adult age (forty days). Directly following this exposure, the offspring lungs were examined for markers related to oxidative stress; oxidative phosphorylation; and mitochondrial fusion, fission, biogenesis, and mitophagy. Acute ozone exposure significantly increased pulmonary oxidant status and upregulated the molecular machinery that controls receptor-mediated mitophagy. In female offspring, a perinatal HFD exacerbated these responses, whereas in male offspring, responses were similar for both diet groups. The expression of the genes and proteins involved in oxidative phosphorylation and mitochondrial biogenesis, fusion, and fission was not affected by ozone exposure or perinatal HFD. These findings suggest that a perinatal HFD influences ozone-induced responses on pulmonary oxidant status and the molecular control of mitophagy in female rat offspring.

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