scholarly journals High-Fat Intake During Pregnancy and Lactation Exacerbates High-Fat Diet-Induced Complications in Male Offspring in Mice

Endocrinology ◽  
2013 ◽  
Vol 154 (10) ◽  
pp. 3565-3576 ◽  
Author(s):  
Michael Kruse ◽  
Yoshinori Seki ◽  
Patricia M. Vuguin ◽  
Xiu Quan Du ◽  
Ariana Fiallo ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Normal Diet ◽  
Fat Intake ◽  
Wild Type ◽  
High Fat ◽  
Low Fat Diet ◽  
Insulin Tolerance ◽  
Normal Chow ◽  
Pregnancy And Lactation

Altered fetal environments, such as a high-fat milieu, induce metabolic abnormalities in offspring. Different postnatal environments reveal the predisposition for adult diseases that occur during the fetal period. This study investigates the ability of a maternal high-fat diet (HFD) to program metabolic responses to HFD reexposure in offspring after consuming normal chow for 23 weeks after weaning. Wild-type CD1 females were fed a HFD (H) or control (C) chow during pregnancy and lactation. At 26 weeks of age, offspring were either reexposed (H-C-H) or newly exposed (C-C-H) to the HFD for 19 weeks. Body weight was measured weekly, and glucose and insulin tolerance were measured after 10 and 18 weeks on the HFD. The metabolic profile of offspring on a HFD or C diet during pregnancy and lactation and weaned onto a low-fat diet was similar at 26 weeks. H-C-H offspring gained more weight and developed larger adipocytes after being reintroduced to the HFD later in life than C-C-H. H-C-H mice were glucose and insulin intolerant and showed reduced gene expression of cox6a2 and atp5i in muscle, indicating mitochondrial dysfunction. In adipocytes, the expression of slc2a4, srebf1, and adipoq genes was decreased in H-C-H mice compared with C-C-C, indicating insulin resistance. H-C-H showed extensive hepatosteatosis, accompanied by increased gene expression for cd36 and serpin1, compared with C-C-H. Perinatal exposure to a HFD programs a more deleterious response to a HFD challenge later in life even after an interval of normal diet in mice.

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.

scholarly journals Gypenosides Altered Hepatic Bile Acids Homeostasis in Mice Treated with High Fat Diet

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yanliu Lu ◽  
Yimei Du ◽  
Lin Qin ◽  
Di Wu ◽  
Wei Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bile Acids ◽  
High Fat Diet ◽  
Lipid Level ◽  
Density Lipoprotein ◽  
Serum Lipid Level ◽  
Normal Diet ◽  
High Fat ◽  
Expression Levels ◽  
Conjugated Bile Acids

Gypenosides extracted from Gynostemma pentaphyllum (Thunb.) Makino have significant role in reducing serum lipid level and treating fatty liver diseases, however, without clear mechanism. As gypenosides share the similar core structures with bile acids (the endogenous ligands of nuclear receptor FXR), we hypothesize that gypenosides may improve hypercholesterolemia via FXR-mediated bile acids signaling. The present study was designed to validate the role of gypenosides in reducing levels of serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), as well as in regulating bile acids homeostasis and related gene expression levels. The C57BL/6 male mice were divided into four groups. Mice in groups ND and HFD were fed with normal diet and high fat diet for 38 weeks, respectively. In groups HFD+GP and HFD+ST, mice were fed with high fat diet for 38 weeks and treated with gypenosides and simvastatin (positive control) from weeks 16 to 38, respectively. Serum TC and LDL-C levels were assayed by commercially available kits. Expression levels of genes were tested by the quantitative real-time PCR. The LC-MS/MS was applied to quantify major bile acids in mice livers. Our results showed that gypenosides significantly decreased serum TC and LDL-C levels. The gene expression level of Shp was downregulated while the levels of Cyp7a1, Cyp8b1, Fxr, Lrh1, Jnk1/2, and Erk1/2 were upregulated by gypenosides. Indicated by LC-MS/MS technology, gypenosides increased the hepatic levels of several free bile acids and most taurine-conjugated bile acids while decreasing glycine-conjugated bile acids levels. In addition, gypenosides decreased the CA/CDCA ratio. Gypenosides may improve the abnormal lipid profile of HFD-fed mice via two pathways: (1) enhancing the bile acids biosynthesis from cholesterol; (2) decreasing the CA/CDCA ratio which is positively related to cholesterol absorption.

Abstract 657: A New Translational Model of Hypercholesterolemia and Atherosclerosis: Effect of Statins on LDLR KO Miniature Swine

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Dale E Mais ◽  
Thomas Vihtelic ◽  
Chidozie Amuzie ◽  
Steven Denham ◽  
John R Swart ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Clinical Chemistry ◽  
Small Animal ◽  
Normal Diet ◽  
Large Animal Model ◽  
Control Group ◽  
Large Animal ◽  
Wild Type ◽  
High Fat ◽  
Miniature Swine

Small animal models of atherosclerosis are commonly used in drug studies; however, the results often fail to translate into the clinic. A large animal model that more accurately reflects the human disease is needed. We recently developed a transgenic Yucatan pig model in which the LDL receptor (LDLR) gene is knocked out. Five groups of Yucatan pigs (N=4 per group), either wild type (LDLR+/+) or heterozygote (LDLR+/-) were fed a normal diet or a high fat diet for a six month period. One of the heterozygote/high fat diet groups in addition received a daily dose of a statin (atorvastatin) at 3 mg/kg. Every two weeks during the study a variety of clinical chemistry parameters were measured. At study termination, select arteries were collected, stained for lipid deposits and quantitated. In addition, sections of these arteries were prepared for immunohistochemistry to detect selected markers of macrophage infiltration into the atherosclerotic plaques. As expected, pigs fed a high fat diet gained significantly more weight at six months whether they were wild type or LDLR+/-. Atorvastatin appeared to attenuate this weight gain. There were significant increases in total cholesterol, HDL and LDL in pigs fed the high fat diet compared to their corresponding control group. The group receiving the atorvastatin had reduced values of these parameters compared to controls showing that a statin had a beneficial effect on lipid levels even in a high fat diet scenario. VLDL levels were not affected but there were triglyceride changes across the groups. Liver function was unchanged based on total bilirubin and AST while ALT measurements were altered in some of the groups. Immunohistochemistry and histomorphometry was performed on some arteries. Atorvastatin-induced amelioration of hypercholesterolemia in this model underscores its translational utility.

scholarly journals ADAR1 deficiency protects against high-fat diet-induced obesity and insulin resistance in mice

2020 ◽  
Author(s):  
Xiaobing Cui ◽  
Jia Fei ◽  
Sisi Chen ◽  
Gaylen L. Edwards ◽  
Shi-You Chen
Keyword(s):  
Insulin Resistance ◽  
Food Intake ◽  
High Fat Diet ◽  
Peptide Yy ◽  
Tolerance Test ◽  
Chow Diet ◽  
High Fat ◽  
Blood Biochemical ◽  
Insulin Tolerance ◽  
Normal Chow

Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases, and many other chronic diseases. The objective of this study was to determine the role of adenosine deaminase acting on RNA 1 (ADAR1) in the development of obesity and insulin resistance. Wild-type (WT) and heterozygous ADAR1-deficient (Adar1+/-) mice were fed normal chow or high-fat diet (HFD) for 12 weeks. Adar1+/- mice fed with HFD exhibited a lean phenotype with reduced fat mass compared with WT controls, although no difference was found under chow diet conditions. Blood biochemical analysis and insulin tolerance test showed that Adar1+/- improved HFD-induced dyslipidemia and insulin resistance. Metabolic studies showed that food intake was decreased in Adar1+/- mice compared with the WT mice under HFD conditions. Paired feeding studies further demonstrated that Adar1+/- protected mice from HFD-induced obesity through decreased food intake. Furthermore, Adar1+/- restored the increased ghrelin expression in stomach and the decreased serum peptide YY levels under HFD conditions. These data indicate that ADAR1 may contribute to diet-induce obesity, at least partially, through modulating the ghrelin and peptide YY expression and secretion.

scholarly journals Differential Effects of Maternal High Fat Diet During Pregnancy and Lactation on Taste Preferences in Rats

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3553
Author(s):  
Gabor C. Mezei ◽  
Serdar H. Ural ◽  
Andras Hajnal
Keyword(s):  
High Fat Diet ◽  
Metabolic Disorders ◽  
Taste Preference ◽  
Normal Diet ◽  
Taste Preferences ◽  
Adult Offspring ◽  
High Fat ◽  
Preference Testing ◽  
Pregnancy And Lactation ◽  
The Impact

Maternal intake of high fat diet (HFD) increases risk for obesity and metabolic disorders in offspring. Developmental programming of taste preference is a potential mechanism by which this occurs. Whether maternal HFD during pregnancy, lactation, or both, imposes greater risks for altered taste preferences in adult offspring remains a question, and in turn, was investigated in the present study. Four groups of offspring were generated based on maternal HFD access: (1) HFD during pregnancy and lactation (HFD); (2) HFD during pregnancy (HFD-pregnancy); (3) HFD during lactation (HFD-lactation); and (4) normal diet (ND) during pregnancy and lactation (ND). Adult offspring 70 days of age underwent sensory and motivational taste preference testing with various concentrations of sucrose and Intralipid solutions using brief-access automated gustometers (Davis-rigs) and 24 h two-bottle choice tests, respectively. To control for post-gestational diet effects, offspring in all experimental groups were weaned on ND, and did not differ in body weight or glucose tolerance at the time of testing. Offspring exposed to maternal HFD showed increased sensory taste responses for 0.3, 0.6, 1.2 M sucrose solutions in HFD and 0.6 M in HFD-pregnancy groups, compared to animals exposed to ND. Similar effects were noted for lower concentrations of Intralipid in HFD (0.05, 0.10%) and HFD-pregnancy (0.05, 0.10, 0.5%) groups. The HFD-lactation group showed an opposite, diminished responsiveness for sucrose at the highest concentrations (0.9, 1.2, 1.5 M), but not for Intralipid, compared to ND animals. Extended-access two-bottle tests did not reveal major difference across the groups. Our study shows that maternal HFD during pregnancy and lactation has markedly different effects on preferences for palatable sweet and fatty solutions in adult offspring and suggests that such developmental programing may primarily affect gustatory mechanisms. Future studies are warranted for determining the impact of taste changes on development of obesity and metabolic disorders in a “real” food environment with food choices available, as well as to identify specific underlying mechanisms.

Adipose depot-specific modulation of angiotensinogen gene expression in diet-induced obesity

2004 ◽  
Vol 286 (6) ◽  
pp. E891-E895 ◽  
Author(s):  
Kamal Rahmouni ◽  
Allyn L. Mark ◽  
William G. Haynes ◽  
Curt D. Sigmund
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Rnase Protection Assay ◽  
Regulatory Sequences ◽  
High Fat ◽  
Rnase Protection ◽  
Brown Adipose ◽  
Normal Chow ◽  
Plasma Leptin

Adipose tissue represents an important source of angiotensinogen (AGT). We investigated the effect of obesity induced by a high-fat diet on the expression of mouse (mAGT) and human AGT (hAGT) genes in liver, kidney, and heart and different adipose depots in normal mice (C57BL/6J), and in transgenic mice expressing the hAGT gene under the control of its own promoter. Mice were fed a high-fat diet (45% kcal) or normal chow (10% kcal) for 10 and 20 wk. The expression of mAGT and hAGT mRNA was quantified using an RNAse protection assay. Mice on the high-fat diet exhibited increased weight, fat mass, and plasma leptin. Expression of mAGT or hAGT genes was not affected by high-fat diet in nonadipose tissues, brown adipose tissue, or subcutaneous white fat. In contrast, high-fat diet increased both mAGT and hAGT gene expression in visceral adipose depots (omental, reproductive, and perirenal fat). Thus obesity-induced by a high-fat diet is associated with a tissue-specific increased expression of both mouse and human AGT genes in intra-abdominal adipose tissue. Our findings also suggest that 1.2 kb of regulatory sequences present in the hAGT transgene are sufficient to transcriptionally respond to a high-fat diet in an adipose-specific and depot-specific manner.

scholarly journals Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice

2016 ◽  
Vol 310 (11) ◽  
pp. E886-E899 ◽  
Author(s):  
Pia Kiilerich ◽  
Lene Secher Myrmel ◽  
Even Fjære ◽  
Qin Hao ◽  
Floor Hugenholtz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Gut Microbiota ◽  
Dietary Fat ◽  
High Fat Diet ◽  
High Fat ◽  
Low Fat ◽  
Low Fat Diet ◽  
Low Protein

Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein/sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue, affecting pathways related to metabolism and inflammation. Analysis of fecal bacterial DNA using the Mouse Intestinal Tract Chip revealed significant changes in the composition of the gut microbiota in relation to host age and dietary fat content, but not the protein/sucrose ratio. Accordingly, dietary fat rather than the protein/sucrose ratio or adiposity is a major driver shaping the gut microbiota, whereas the effect of a high-fat diet on survival is dependent on the protein/sucrose ratio.

scholarly journals Gene Expression Analysis of the Anti-obesity Effect by Apple Polyphenols in Rats Fed a High Fat Diet or a Normal Diet

2006 ◽  
Vol 55 (6) ◽  
pp. 305-314 ◽  
Author(s):  
Yutaka OHTA ◽  
Manabu SAMI ◽  
Tomomasa KANDA ◽  
Kenji SAITO ◽  
Kyoichi OSADA ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
High Fat Diet ◽  
Gene Expression Analysis ◽  
Normal Diet ◽  
High Fat
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