scholarly journals The Molecular Effects of a High Fat Diet on Endometrial Tumour Biology

Life ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 188
Author(s):  
Michael Wilkinson ◽  
Piriyah Sinclair ◽  
Ludmilla Dellatorre-Teixeira ◽  
Patrick Swan ◽  
Eoin Brennan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Weight Gain ◽  
Rat Model ◽  
High Fat Diet ◽  
Cancer Metastasis ◽  
Chow Diet ◽  
Suitable Model ◽  
High Fat ◽  
Diet Induced Obesity

We sought to validate the BDII/Han rat model as a model for diet-induced obesity in endometrial cancer (EC) and determine if transcriptomic changes induced by a high fat diet (HFD) in an EC rat model can be used to identify novel biomarkers in human EC. Nineteen BDII/Han rats were included. Group A (n = 7) were given ad lib access to a normal calorie, normal chow diet (NCD) while Group B (n = 12) were given ad lib access to a calorie rich HFD for 15 months. RNAseq was performed on endometrial tumours from both groups. The top-ranking differentially expressed genes (DEGs) were examined in the human EC using The Cancer Genome Atlas (TCGA) to assess if the BDII/Han rat model is an appropriate model for human obesity-induced carcinogenesis. Weight gain in HFD rats was double the weight gain of NCD rats (50 g vs. 25 g). The incidence of cancer was similar in both groups (4/7—57% vs. 4/12—33%; p = 0.37). All tumours were equivalent to a Stage 1A, Grade 2 human endometrioid carcinoma. A total of 368 DEGs were identified between the tumours in the HFD group compared to the NCD group. We identified two upstream regulators of the DEGs, mir-33 and Brd4, and a pathway analysis identified downstream enrichment of the colorectal cancer metastasis and ovarian cancer metastasis pathways. Top-ranking DEGs included Tex14, A2M, Hmgcs2, Adamts5, Pdk4, Crabp2, Capn12, Npw, Idi1 and Gpt. A2M expression was decreased in HFD tumours. Consistent with these findings, we found a significant negative correlation between A2M mRNA expression levels and BMI in the TCGA cohort (Spearman’s Rho = −0.263, p < 0.001). A2M expression was associated with improved overall survival (HR = 0.45, 95% CI 0.23–0.9, p = 0.024). Crabp2 expression was increased in HFD tumours. In human EC, CRABP2 expression was associated with reduced overall survival (HR = 3.554, 95% CI 1.875–6.753, p < 0.001). Diet-induced obesity can alter EC transcriptomic profiles. The BDII/Han rat model is a suitable model of diet-induced obesity in endometrial cancer and can be used to identify clinically relevant biomarkers in human EC.

scholarly journals Weight Loss in Response to Food Deprivation Predicts The Extent of Diet Induced Obesity in C57BL/6J Mice

2014 ◽  
Author(s):  
Matthew J. Peloqiun ◽  
Dave Bridges
Keyword(s):  
Weight Loss ◽  
Weight Gain ◽  
Food Deprivation ◽  
High Fat Diet ◽  
Control Diet ◽  
Chow Diet ◽  
High Fat ◽  
Strong Negative Correlation ◽  
Diet Induced Obesity ◽  
Serum Hormone

Inbred C57BL/6J mice have been used to study diet-induced obesity and the detrimental physiological effects associated with it. Little is understood about predictive factors that predispose an animal to weight gain. To address this, mice were fed a high fat diet, control diet or normal chow diet. Several measurements including pre-diet serum hormone levels and pre-diet body weight were analyzed, but these had limited predictive value regarding weight gain. However, baseline measurements of weight loss in response to food deprivation showed a strong negative correlation with high fat diet-induced weight gain. These data suggest that fasting-induced weight loss in adolescent mice is a useful predictor of diet-induced weight gain.

scholarly journals Anxiety induced by extra-hypothalamic BDNF deficiency instigates resistance to diet-induced obesity

2018 ◽  
Author(s):  
Xiangyang Xie ◽  
Haili Yang ◽  
Juan Ji An ◽  
Guey-Ying Liao ◽  
Zhi-Xiang Xu ◽  
...  
Keyword(s):  
Weight Gain ◽  
High Fat Diet ◽  
Basal Metabolism ◽  
Chow Diet ◽  
Weight Changes ◽  
High Fat ◽  
Body Weight Changes ◽  
Adaptive Thermogenesis ◽  
Diet Induced Obesity ◽  
Anxiety Levels

SUMMARYAnxiety disorders are associated with body weight changes in humans. However, mechanisms underlying anxiety-related weight changes remain poorly understood. Using Emx1Cre/+ mice, we deleted the gene for brain-derived neurotrophic factor (BDNF) in the cortex, hippocampus, and some parts of the amygdala. The resulting mutant mice displayed elevated anxiety levels and were markedly lean when fed either chow diet or high-fat diet (HFD). The mice showed higher levels of sympathetic activity, thermogenesis and lipolysis in both brown and white adipose tissues, and higher oxygen consumption and body temperature, compared with control mice. They were still lean at thermoneurality when fed HFD, indicating elevated basal metabolism in addition to activated thermogenesis. Anxiety induced by site-specific Bdnf deletion similarly increased energy expenditure and minimized HFD-induced weight gain. These results reveal that anxiety can stimulate adaptive thermogenesis and basal metabolism by activating sympathetic nervous system, which enhances lipolysis and limits weight gain.

scholarly journals Partial Deficiency of Zfp217 Resists High-Fat Diet-Induced Obesity by Increasing Energy Metabolism in Mice

2021 ◽  
Vol 22 (10) ◽  
pp. 5390
Author(s):  
Qianhui Zeng ◽  
Nannan Wang ◽  
Yaru Zhang ◽  
Yuxuan Yang ◽  
Shuangshuang Li ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Energy Metabolism ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Chow Diet ◽  
High Fat ◽  
Glycolipid Metabolism ◽  
Partial Deficiency

Obesity-induced adipose tissue dysfunction and disorders of glycolipid metabolism have become a worldwide research priority. Zfp217 plays a crucial role in adipogenesis of 3T3-L1 preadipocytes, but about its functions in animal models are not yet clear. To explore the role of Zfp217 in high-fat diet (HFD)-induced obese mice, global Zfp217 heterozygous knockout (Zfp217+/−) mice were constructed. Zfp217+/− mice and Zfp217+/+ mice fed a normal chow diet (NC) did not differ significantly in weight gain, percent body fat mass, glucose tolerance, or insulin sensitivity. When challenged with HFD, Zfp217+/− mice had less weight gain than Zfp217+/+ mice. Histological observations revealed that Zfp217+/− mice fed a high-fat diet had much smaller white adipocytes in inguinal white adipose tissue (iWAT). Zfp217+/− mice had improved metabolic profiles, including improved glucose tolerance, enhanced insulin sensitivity, and increased energy expenditure compared to the Zfp217+/+ mice under HFD. We found that adipogenesis-related genes were increased and metabolic thermogenesis-related genes were decreased in the iWAT of HFD-fed Zfp217+/+ mice compared to Zfp217+/− mice. In addition, adipogenesis was markedly reduced in mouse embryonic fibroblasts (MEFs) from Zfp217-deleted mice. Together, these data indicate that Zfp217 is a regulator of energy metabolism and it is likely to provide novel insight into treatment for obesity.

Ameliorative effect of selegiline in high fat diet induced obesity rat model: Possible role of dopaminergic pathway

2020 ◽  
Vol 20 ◽  
pp. 100301
Author(s):  
Amit Goyal ◽  
Ankita Sharma ◽  
Deepika Sharma ◽  
Tapan Behl ◽  
Anjoo Kamboj ◽  
...  
Keyword(s):  
Rat Model ◽  
High Fat Diet ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Dopaminergic Pathway ◽  
Ameliorative Effect

scholarly journals Reversal of Diet-Induced Obesity Increases Insulin Transport into Cerebrospinal Fluid and Restores Sensitivity to the Anorexic Action of Central Insulin in Male Rats

Endocrinology ◽  
2013 ◽  
Vol 154 (3) ◽  
pp. 1047-1054 ◽  
Author(s):  
Denovan P. Begg ◽  
Joram D. Mul ◽  
Min Liu ◽  
Brianne M. Reedy ◽  
David A. D'Alessio ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Food Intake ◽  
High Fat Diet ◽  
Male Rats ◽  
Control Group ◽  
Chow Diet ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Insulin Transport ◽  
The Central Nervous System

Abstract Diet-induced obesity (DIO) reduces the ability of centrally administered insulin to reduce feeding behavior and also reduces the transport of insulin from the periphery to the central nervous system (CNS). The current study was designed to determine whether reversal of high-fat DIO restores the anorexic efficacy of central insulin and whether this is accompanied by restoration of the compromised insulin transport. Adult male Long-Evans rats were initially maintained on either a low-fat chow diet (LFD) or a high-fat diet (HFD). After 22 weeks, half of the animals on the HFD were changed to the LFD, whereas the other half continued on the HFD for an additional 8 weeks, such that there were 3 groups: 1) a LFD control group (Con; n = 18), 2) a HFD-fed, DIO group (n = 17), and 3) a HFD to LFD, DIO-reversal group (DIO-rev; n = 18). The DIO reversal resulted in a significant reduction of body weight and epididymal fat weight relative to the DIO group. Acute central insulin administration (8 mU) reduced food intake and caused weight loss in Con and DIO-rev but not DIO rats. Fasting cerebrospinal fluid insulin was higher in DIO than Con animals. However, after a peripheral bolus injection of insulin, cerebrospinal fluid insulin increased in Con and DIO-rev rats but not in the DIO group. These data provide support for previous reports that DIO inhibits both the central effects of insulin and insulin's transport to the CNS. Importantly, DIO-rev restored sensitivity to the effects of central insulin on food intake and insulin transport into the CNS.

scholarly journals SIM1 Overexpression Partially Rescues Agouti Yellow and Diet-Induced Obesity by Normalizing Food Intake

Endocrinology ◽  
2006 ◽  
Vol 147 (10) ◽  
pp. 4542-4549 ◽  
Author(s):  
Bassil M. Kublaoui ◽  
J. Lloyd Holder ◽  
Kristen P. Tolson ◽  
Terry Gemelli ◽  
Andrew R. Zinn
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Transgenic Mice ◽  
High Fat Diet ◽  
Chow Diet ◽  
High Fat ◽  
Enhanced Sensitivity ◽  
Diet Induced Obesity ◽  
Melanocortin 4 Receptor ◽  
Obesity In Mice

Single-minded 1 (SIM1) mutations are associated with obesity in mice and humans. Haploinsufficiency of mouse Sim1 causes hyperphagic obesity with increased linear growth and enhanced sensitivity to a high-fat diet, a phenotype similar to that of agouti yellow and melanocortin 4 receptor knockout mice. To investigate the effects of increased Sim1 dosage, we generated transgenic mice that overexpress human SIM1 and examined their phenotype. Compared with wild-type mice, SIM1 transgenic mice had no obvious phenotype on a low-fat chow diet but were resistant to diet-induced obesity on a high-fat diet due to reduced food intake with no change in energy expenditure. The SIM1 transgene also completely rescued the hyperphagia and partially rescued the obesity of agouti yellow mice, in which melanocortin signaling is abrogated. Our results indicate that the melanocortin 4 receptor signals through Sim1 or its transcriptional targets in controlling food intake but not energy expenditure.

scholarly journals Leptin resistance: a prediposing factor for diet-induced obesity

2009 ◽  
Vol 296 (3) ◽  
pp. R493-R500 ◽  
Author(s):  
Philip J. Scarpace ◽  
Yi Zhang
Keyword(s):  
Weight Gain ◽  
Leptin Receptor ◽  
Causative Factor ◽  
Leptin Resistance ◽  
Chow Diet ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Dietary Fructose ◽  
Complex Chronic Disease ◽  
Obesity Syndrome

Obesity is a resilient and complex chronic disease. One potential causative factor in the obesity syndrome is leptin resistance. Leptin behaves as a potent anorexic and energy-enhancing hormone in most young or lean animals, but its effects are diminished or lacking in the obese state associated with a normal genetic background. Emerging evidence suggests that leptin resistance predisposes the animal to exacerbated diet-induced obesity (DIO). Elevation of central leptin in young, lean rats induces a leptin resistance that precludes obesity on a chow diet but accelerates high-fat (HF)-induced obesity. Similarly, chronic dietary fructose consumption evokes a leptin resistance that causes obesity only upon HF exposure. Inherent central leptin insensitivity also contributes to dietary weight gain in certain obesity-prone rats. Conversely, aged, leptin-resistant animals are obese with continuous chow feeding and demonstrate aggravated obesity when challenged with an HF diet. Additionally, a submaximal central blockade with a leptin antagonist leads to obesity on both chow and HF diets, as is the case in rodents with leptin receptor deficiency of genetic origin. Despite the differences in the incidence of obesity on a chow diet, all of these forms of leptin resistance predispose rodents to aggravated HF-mediated obesity. Moreover, once leptin resistance takes hold, it aggravates DIO, and the leptin resistance and obesity compound one another, promoting a vicious cycle of escalating weight gain.

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