scholarly journals The Intrauterine and Nursing Period Is a Window of Susceptibility for Development of Obesity and Intestinal Tumorigenesis by a High Fat Diet inMin/+Mice as Adults

2015 ◽  
Vol 2015 ◽  
pp. 1-25
Author(s):  
Ha Thi Ngo ◽  
Ragna Bogen Hetland ◽  
Inger-Lise Steffensen
Keyword(s):  
High Fat Diet ◽  
Tumor Development ◽  
Adult Life ◽  
Tolerance Test ◽  
In Utero ◽  
Negative Control ◽  
Wild Type ◽  
Intestinal Tumorigenesis ◽  
Intestinal Neoplasia ◽  
Small Intestinal

We studied how obesogenic conditions during various life periods affected obesity and intestinal tumorigenesis in adult C57BL/6J-Min(multiple intestinal neoplasia)/+ mice. The mice were given a 10% fat diet throughout life (negative control) or a 45% fat dietin utero, during nursing, during bothin uteroand nursing, during adult life, or during their whole life-span, and terminated at 11 weeks for tumorigenesis (Min/+) or 23 weeks for obesogenic effect (wild-type). Body weight at 11 weeks was increased after a 45% fat diet during nursing, during bothin uteroand nursing, and throughout life, but had normalized at 23 weeks. In the glucose tolerance test, the early exposure to a 45% fat dietin utero, during nursing, or during bothin uteroand nursing, did not affect blood glucose, whereas a 45% fat diet given to adults or throughout life did. However, a 45% fat diet during nursing or duringin uteroand nursing increased the number of small intestinal tumors. So did exposures to a 45% fat diet in adult life or throughout life, but without increasing the tumor numbers further. The intrauterine and nursing period is a window of susceptibility for dietary fat-induced obesity and intestinal tumor development.

scholarly journals Genetic and Diet-Induced Obesity Increased Intestinal Tumorigenesis in the Double Mutant Mouse Model Multiple Intestinal Neoplasia X Obese via Disturbed Glucose Regulation and Inflammation

2015 ◽  
Vol 2015 ◽  
pp. 1-21 ◽  
Author(s):  
Ha Thi Ngo ◽  
Ragna Bogen Hetland ◽  
Unni Cecilie Nygaard ◽  
Inger-Lise Steffensen
Keyword(s):  
Glucose Regulation ◽  
Wild Type ◽  
Intestinal Tumors ◽  
Intestinal Tumorigenesis ◽  
Diet Induced Obesity ◽  
Intestinal Neoplasia ◽  
Gene Coding ◽  
Induced Tumors ◽  
Small Intestinal ◽  
Double Mutant Mouse

We have studied how spontaneous or carcinogen-induced intestinal tumorigenesis was affected by genetic or diet-induced obesity in C57BL/6J-ApcMin/+X C57BL/6J-Lepob/+mice. Obesity was induced by theobese(ob) mutation in thelepgene coding for the hormone leptin, or by a 45% fat diet. The effects of obesity were examined on spontaneous intestinal tumors caused by themultiple intestinal neoplasia(Min) mutation in theadenomatous polyposis coli(Apc) gene and on tumors induced by the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). F1 ob/ob (homozygous mutated) mice had increased body weight (bw) and number of spontaneous and PhIP-induced small intestinal tumors (inApcMin/+mice), versus ob/wt (heterozygous mutated) and wt/wt mice (homozygous wild-type). A 45% fat diet exacerbated bw and spontaneous tumor numbers versus 10% fat, but not PhIP-induced tumors. Except for bw, ob/wt and wt/wt were not significantly different. The obesity caused hyperglucosemia and insulinemia in ob/ob mice. A 45% fat diet further increased glucose, but not insulin. Inflammation was seen as increased TNFαlevels in ob/ob mice. Thus the results implicate disturbed glucose regulation and inflammation as mechanisms involved in the association between obesity and intestinal tumorigenesis. Ob/ob mice had shorter lifespan than ob/wt and wt/wt mice.

Abstract P312: The Essential Role Of Prak In Preserving Cardiac Function And Insulin Resistance In High Fat Diet-induced Diabetes

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Yu T Zhao ◽  
Jianfeng Du ◽  
Thomas J Zhao ◽  
Hao Wang ◽  
Marshall Kadin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiac Function ◽  
Western Blot ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Tolerance Test ◽  
Wild Type ◽  
High Fat

Background: p38 regulated/activated protein kinase (PRAK) plays a crucial role in modulating cell death and survival. However, the role of PRAK in mediating cardiac dysfunction and metabolic disorders remains unclear. We examined the effects of deletion of PRAK on modulating cardiac function and insulin resistance in mice exposed to a high fat diet (HFD). Methods: Wild type and PRAK -/- mice at 8 weeks old were exposed to either chow food or HFD for a consecutive 16 weeks. Glucose tolerance test and insulin tolerance test were employed to assess insulin resistance. Echocardiography was employed to assess myocardial function. Western blot was used to determine the molecular signaling involved in phosphorylation of IRS-1, AMPKα, ERK-44/42, and irisin. Real time-PCR was used to assess the hypertrophic genes of the myocardium. Histological analysis was employed to assess the hypertrophic response, interstitial myocardial fibrosis, and apoptosis in the heart. Results: HFD induced metabolic stress is indicated by glucose intolerance and insulin intolerance. PRAK knockout aggravated insulin resistance, as indicated by glucose intolerance and insulin intolerance testing as compared to wild type littermates. As compared to wild type, hyperglycemia and hypercholesterolemia were manifested in PRAK-knockout mice following high fat diet intervention. High fat diet intervention displayed a decline in fractional shortening (FS) and ejection fraction (EF). However, deletion of PRAK exacerbated the decline in EF and FS as compared to wild type mice following HFD treatment. In addition, PRAK knockout mice enhanced the expression of myocardial hypertrophic genes including ANP, BNP, and βMHC in HFD treatment, which was also associated with an increase in cardiomyocyte size and interstitial fibrosis. Western blot indicated that deletion of PRAK induces decreases in phosphorylation of IRS-1, AMPKα, and ERK44/42 as compared to wild type controls. Conclusion: Our finding indicates that deletion of PRAK promoted myocardial dysfunction, cardiac remodeling, and metabolic disorders in response to HFD.

The impact of commercial rodent diets on the induction of tumours and flat aberrant crypt foci in the intestine of multiple intestinal neoplasia mice

2012 ◽  
Vol 46 (3) ◽  
pp. 207-214 ◽  
Author(s):  
Camilla Svendsen ◽  
Jan Alexander ◽  
Jan Erik Paulsen ◽  
Helle K Knutsen ◽  
Hege Hjertholm ◽  
...  
Keyword(s):  
Small Intestine ◽  
Mouse Model ◽  
Precancerous Lesions ◽  
Aberrant Crypt Foci ◽  
Intestinal Tumorigenesis ◽  
Tumour Development ◽  
Intestinal Neoplasia ◽  
Small Intestinal ◽  
The Impact ◽  
Colonic Tumours

A large variation in spontaneous tumour development in the multiple intestinal neoplasia (Min) mouse model between laboratories has been reported. The composition of the diet might be an important factor. We examined the impact of five commercial rodent diets: the natural ingredient breeding diet Harlan Teklad 2018 (HT), the purified breeding diet AIN93G, the natural ingredient maintenance diet RM1, and the purified maintenance diets AIN93M and AIN76A, on the spontaneous intestinal tumorigenesis in the Min mouse model. The Min mice were fed one of two breeding diets during gestation and until four weeks of age, thereafter one of the three maintenance diets. Min mice bred on the breeding diet HT had significantly higher numbers and incidences of tumours in the colon, but fewer tumours in the small intestine than the breeding diet AIN93G. The maintenance diet RM1 gave a significantly higher number of small intestinal and colonic tumours and precancerous lesions called flat aberrant crypt foci (ACF) compared with the maintenance diets AIN93M and AIN76A. These findings show the importance of defining the type of diet used in experimental intestinal carcinogenesis studies, and that the diet should be taken into consideration when comparing results from different studies with Min mice.

Comparison of streptozotocin-induced diabetes at different moments of the life of female rats for translational studies

2021 ◽  
pp. 002367722110018
Author(s):  
Yuri K Sinzato ◽  
Eduardo Klöppel ◽  
Carolina A Miranda ◽  
Verônyca G Paula ◽  
Larissa F Alves ◽  
...  
Keyword(s):  
Adult Life ◽  
Tolerance Test ◽  
Full Term ◽  
Female Rats ◽  
Lower Percentage ◽  
Control Group ◽  
Oral Glucose ◽  
Postnatal Life ◽  
Sprague Dawley ◽  
Term Pregnancy

Animal models are widely used for studying diabetes in translational research. However, methods for induction of diabetes are conflicting with regards to their efficacy, reproducibility and cost. A comparison of outcomes between the diabetic models is still unknown, especially full-term pregnancy.To understand the comparison, we analyzed the streptozotocin (STZ)-induced diabetes at three life-different moments during the neonatal period in Sprague–Dawley female rats: at the first (D1), second (D2) and fifth (D5) day of postnatal life. At adulthood (90 days; D90), the animals were submitted to an oral glucose tolerance test (OGTT) for diabetic status confirmation. The diabetic and control rats were mated and sacrificed at full-term pregnancy for different analyses. Group D1 presented a higher mortality percentage after STZ administration than groups D2 and D5. All diabetic groups presented higher blood glucose levels as compared to those of the control group, while group D5 had higher levels of glycemia compared with other groups during OGTT. The diabetic groups showed impaired reproductive outcomes compared with the control group. Group D1 had lower percentages of mated rats and D5 showed a lower percentage of a full-term pregnancy. Besides that, these two groups also showed the highest percentages of inadequate fetal weight. In summary, although all groups fulfill the diagnosis criteria for diabetes in adult life, in our investigation diabetes induced on D5 presents lower costs and higher efficacy and reproducibility for studies involving diabetes-complicated pregnancy.

scholarly journals PINK1 deficiency impairs adult neurogenesis of dopaminergic neurons

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sarah J. Brown ◽  
Ibrahim Boussaad ◽  
Javier Jarazo ◽  
Julia C. Fitzgerald ◽  
Paul Antony ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Neurodegenerative Disorders ◽  
Dopaminergic Neurons ◽  
Adult Life ◽  
Lineage Tracing ◽  
Model Systems ◽  
Wild Type ◽  
Therapeutic Approaches ◽  
Early Effect ◽  
Early Adult Life

AbstractRecent evidence suggests neurogenesis is on-going throughout life but the relevance of these findings for neurodegenerative disorders such as Parkinson’s disease (PD) is poorly understood. Biallelic PINK1 mutations cause early onset, Mendelian inherited PD. We studied the effect of PINK1 deficiency on adult neurogenesis of dopaminergic (DA) neurons in two complementary model systems. Zebrafish are a widely-used model to study neurogenesis in development and through adulthood. Using EdU analyses and lineage-tracing studies, we first demonstrate that a subset of ascending DA neurons and adjacent local-projecting DA neurons are each generated into adulthood in wild type zebrafish at a rate that decreases with age. Pink1-deficiency impedes DA neurogenesis in these populations, most significantly in early adult life. Pink1 already exerts an early effect on Th1+ progenitor cells rather than on differentiated DA neurons only. In addition, we investigate the effect of PINK1 deficiency in a human isogenic organoid model. Global neuronal differentiation in PINK1-deficient organoids and isogenic controls is similar, but PINK1-deficient organoids display impeded DA neurogenesis. The observation of impaired adult dopaminergic neurogenesis in Pink1 deficiency in two complementing model systems may have significant consequences for future therapeutic approaches in human PD patients with biallelic PINK1 mutations.

scholarly journals Novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Safia Akhtar ◽  
Silas A. Culver ◽  
Helmy M. Siragy
Keyword(s):  
Protein Expression ◽  
High Fat Diet ◽  
Normal Diet ◽  
Receptor Expression ◽  
Wild Type ◽  
High Fat ◽  
Renal Gluconeogenesis ◽  
Mrna And Protein Expression ◽  
Polymerase Chain ◽  
Renal Expression

AbstractRecent studies suggested that renal gluconeogenesis is substantially stimulated in the kidney in presence of obesity. However, the mechanisms responsible for such stimulation are not well understood. Recently, our laboratory demonstrated that mice fed high fat diet (HFD) exhibited increase in renal Atp6ap2 [also known as (Pro)renin receptor] expression. We hypothesized that HFD upregulates renal gluconeogenesis via Atp6ap2-PGC-1α and AKT pathway. Using real-time polymerase chain reaction, western blot analysis and immunostaining, we evaluated renal expression of the Atp6ap2 and renal gluconeogenic enzymes, PEPCK and G6Pase, in wild type and inducible nephron specific Atp6ap2 knockout mice fed normal diet (ND, 12 kcal% fat) or a high-fat diet (HFD, 45 kcal% fat) for 8 weeks. Compared with ND, HFD mice had significantly higher body weight (23%) (P < 0.05), renal mRNA and protein expression of Atp6ap2 (39 and 35%), PEPCK (44 and 125%) and G6Pase (39 and 44%) respectively. In addition, compared to ND, HFD mice had increased renal protein expression of PGC-1α by 32% (P < 0.05) and downregulated AKT by 33% (P < 0.05) respectively in renal cortex. Atp6ap2-KO abrogated these changes in the mice fed HFD. In conclusion, we identified novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway.

Sign in / Sign up

Export Citation Format

Share Document