scholarly journals Programming With Varying Dietary Fat Content Alters Cardiac Insulin Receptor, Glut4 and FoxO1 Immunoreactivity in Neonatal Rats, Whereas High Fat Programming Alters Cebpa Gene Expression in Neonatal Female Rats

2022 ◽  
Vol 12 ◽  
Author(s):  
Annelene Govindsamy ◽  
Samira Ghoor ◽  
Marlon E. Cerf
Keyword(s):  
Gene Expression ◽  
Insulin Receptor ◽  
Insulin Signaling ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Female Offspring ◽  
Fat Content ◽  
Neonatal Rats ◽  
Cardiac Physiology ◽  
High Fat

Fetal programming refers to an intrauterine stimulus or insult that shapes growth, development and health outcomes. Dependent on the quality and quantity, dietary fats can be beneficial or detrimental for the growth of the fetus and can alter insulin signaling by regulating the expression of key factors. The effects of varying dietary fat content on the expression profiles of factors in the neonatal female and male rat heart were investigated and analyzed in control (10% fat), 20F (20% fat), 30F (30% fat) and 40F (40% fat which was a high fat diet used to induce high fat programming) neonatal rats. The whole neonatal heart was immunostained for insulin receptor, glucose transporter 4 (Glut4) and forkhead box protein 1 (FoxO1), followed by image analysis. The expression of 84 genes, commonly associated with the insulin signaling pathway, were then examined in 40F female and 40F male offspring. Maintenance on diets, varying in fat content during fetal life, altered the expression of cardiac factors, with changes induced from 20% fat in female neonates, but from 30% fat in male neonates. Further, CCAAT/enhancer-binding protein alpha (Cebpa) was upregulated in 40F female neonates. There was, however, differential expression of several insulin signaling genes in 40F (high fat programmed) offspring, with some tending to significance but most differences were in fold changes (≥1.5 fold). The increased immunoreactivity for insulin receptor, Glut4 and FoxO1 in 20F female and 30F male neonatal rats may reflect a compensatory response to programming to maintain cardiac physiology. Cebpa was upregulated in female offspring maintained on a high fat diet, with fold increases in other insulin signaling genes viz. Aebp1, Cfd (adipsin), Adra1d, Prkcg, Igfbp, Retn (resistin) and Ucp1. In female offspring maintained on a high fat diet, increased Cebpa gene expression (concomitant with fold increases in other insulin signaling genes) may reflect cardiac stress and an adaptative response to cardiac inflammation, stress and/or injury, after high fat programming. Diet and the sex are determinants of cardiac physiology and pathophysiology, reflecting divergent mechanisms that are sex-specific.

Metabolic programming of adipose tissue in female C57Bl 6 mice offspring by maternal high fat feeding and obesity results in greater adaptability to dietary fat content and resistance to high fat diet-induced glucose intolerance compared to male mice

2021 ◽  
pp. 1-15
Keyword(s):  
Gene Expression ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Female Offspring ◽  
Male Offspring ◽  
High Fat ◽  
Carnitine Palmitoyl Transferase ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting

Maternal lifestyle influence may be a factor in the worldwide prevalence of obesity and its complications, including diabetes. Studies investigating the effect of the perinatal maternal environment have produced a range of results, sometimes diametrically opposite. The present study was designed to investigate how obesity and weight gain in pregnant mice affects energy balance, body composition and glucose homeostasis in their offspring, both at a young age on standard diet and when older and fed a high-fat diet. At six weeks of age both male and female offspring from mothers fed a high fat diet had a shorter body length than those from mothers fed standard chow. In contrast to males, female offspring also contained a higher proportion of fat and had elevated circulating leptin and adiponectin. Their gonadal fat pads were heavier and contained larger adipocytes, whereas male offspring had proportionally more smaller adipocytes. Six-week-old female, but not male, offspring had increased gonadal fat gene expression of acetyl CoA carboxylase 1, the rate-limiting step in lipid biosynthesis, and decreased gene expression of carnitine palmitoyl transferase 1, the rate-limiting step in fatty acid oxidation. Maternal high fat diet had no effect on glucose tolerance in six-week-old mice, but this was achieved with higher insulin levels in females. Contrastingly, when the offspring were fed a high fat diet for three months, female, but not male, offspring were leaner than those from mothers fed standard chow. Their gonadal fat depots were lighter and the adipocytes were smaller. Female, but not male, offspring fed high fat diet had decreased gonadal fat gene expression of acetyl CoA carboxylase 1, and increased gene expression of carnitine palmitoyl transferase 1. High fat diet-induced glucose intolerance and elevated plasma insulin concentration were improved in female, but not male, offspring. Plasma leptin and adiponectin remained higher in female offspring on high fat diet with resistin levels being lower. These results suggest that the gonadal fat of female offspring is more adaptable to different levels of dietary fat exposure, increasing storage when levels are low and increasing oxidation when levels are high. This may help female offspring be more resistant to the detrimental effects of high fat diet than male mice.

scholarly journals Regulation of plasma leptin in mice: influence of age, high-fat diet, and fasting

1997 ◽  
Vol 273 (1) ◽  
pp. R113-R120 ◽  
Author(s):  
B. Ahren ◽  
S. Mansson ◽  
R. L. Gingerich ◽  
P. J. Havel
Keyword(s):  
Body Weight ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Plasma Insulin ◽  
Plasma Concentrations ◽  
Age Groups ◽  
Fat Content ◽  
High Fat ◽  
Background Strain ◽  
Plasma Leptin

Mechanisms regulating circulating leptin are incompletely understood. We developed a radioimmunoassay for mouse leptin to examine the influence of age, dietary fat content, and fasting on plasma concentrations of leptin in the background strain for the ob/ob mouse, the C57BL/6J mouse. Plasma leptin increased with age [5.3 +/- 0.6 ng/ml at 2 mo (n = 23) vs. 14.2 +/- 1.6 ng/ml at 11 mo (n = 15), P < 0.001]. Across all age groups (2-11 mo, n = 160), log plasma leptin correlated with body weight (r = 0.68, P < 0.0001), plasma insulin (r = 0.38, P < 0.001), and amount of intra-abdominal fat (r = 0.90, P < 0.001), as revealed by magnetic resonance imaging. Plasma leptin was increased by a high-fat diet (58% fat for 10 mo) and reduced by fasting for 48 h. The reduction of plasma leptin was correlated with the reduction of plasma insulin (r = 0.43, P = 0.012) but not with the initial body weight or the change in body weight. Moreover, the reduction in plasma leptin by fasting was impaired by high-fat diet. Thus plasma leptin in C57BL/6J mice 1) increases with age or a high-fat diet; 2) correlates with body weight, fat content, and plasma insulin; and 3) is reduced during fasting by an action inhibited by high-fat diet and related to changes of plasma insulin.

Impact of graded maternal dietary fat content on offspring susceptibility to high‐fat diet in mice

Obesity ◽  
2021 ◽  
Vol 29 (12) ◽  
pp. 2055-2067
Author(s):  
Yi Huang ◽  
Jazmin Osorio Mendoza ◽  
Min Li ◽  
Zengguang Jin ◽  
Baoguo Li ◽  
...  
Keyword(s):  
Dietary Fat ◽  
High Fat Diet ◽  
Fat Content ◽  
High Fat

Effect of High-Fat Diet on Gene Expression of GLUT4 and Insulin Receptor in Soleus Muscle

1994 ◽  
Vol 202 (1) ◽  
pp. 519-526 ◽  
Author(s):  
Y.B. Kim ◽  
T. Tomohiro ◽  
S. Iwashita ◽  
K. Tokuyama ◽  
M. Suzuki
Keyword(s):  
Gene Expression ◽  
Insulin Receptor ◽  
Soleus Muscle ◽  
High Fat Diet ◽  
High Fat

scholarly journals Catalase-dependent H2O2consumption by cardiac mitochondria and redox-mediated loss in insulin signaling

2016 ◽  
Vol 311 (5) ◽  
pp. H1091-H1096 ◽  
Author(s):  
Paul M. Rindler ◽  
Angela Cacciola ◽  
Michael Kinter ◽  
Luke I. Szweda
Keyword(s):  
Oxidative Stress ◽  
Glutathione Peroxidase ◽  
Binding Affinity ◽  
Insulin Signaling ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Cardiac Mitochondria ◽  
High Fat ◽  
Akt Phosphorylation ◽  
Selective Increase

We have recently demonstrated that catalase content in mouse cardiac mitochondria is selectively elevated in response to high dietary fat, a nutritional state associated with oxidative stress and loss in insulin signaling. Catalase and various isoforms of glutathione peroxidase and peroxiredoxin each catalyze the consumption of H2O2. Catalase, located primarily within peroxisomes and to a lesser extent mitochondria, has a low binding affinity for H2O2relative to glutathione peroxidase and peroxiredoxin. As such, the contribution of catalase to mitochondrial H2O2consumption is not well understood. In the current study, using highly purified cardiac mitochondria challenged with micromolar concentrations of H2O2, we found that catalase contributes significantly to mitochondrial H2O2consumption. In addition, catalase is solely responsible for removal of H2O2in nonrespiring or structurally disrupted mitochondria. Finally, in mice fed a high-fat diet, mitochondrial-derived H2O2is responsible for diminished insulin signaling in the heart as evidenced by reduced insulin-stimulated Akt phosphorylation. While elevated mitochondrial catalase content (∼50%) enhanced the capacity of mitochondria to consume H2O2in response to high dietary fat, the selective increase in catalase did not prevent H2O2-induced loss in cardiac insulin signaling. Taken together, our results indicate that mitochondrial catalase likely functions to preclude the formation of high levels of H2O2without perturbing redox-dependent signaling.

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 Nigella sativaRelieves the Altered Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats Fed with a High-Fat Diet

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Mahmoud Balbaa ◽  
Marwa El-Zeftawy ◽  
Doaa Ghareeb ◽  
Nabil Taha ◽  
Abdel Wahab Mandour
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Blood Glucose ◽  
Insulin Receptor ◽  
Lipid Profile ◽  
High Fat Diet ◽  
Diabetic Rats ◽  
High Fat ◽  
Oxidative Stress Parameters ◽  
Stress Parameters

The black cumin (Nigella sativa) “NS” or the black seeds have many pharmacological activities such as antioxidant, anticarcinogenic, antihypertensive, and antidiabetic properties. In this work, streptozotocin-induced diabetic rats fed with a high-fat diet were treated daily with NS oil (NSO) in order to study the effect on the blood glucose, lipid profile, oxidative stress parameters, and the gene expression of some insulin receptor-induced signaling molecules. This treatment was combined also with some drugs (metformin and glimepiride) and the insulin receptor inhibitor I-OMe-AG538. The administration of NSO significantly induced the gene expression of insulin receptor compared to rats that did not receive NSO. Also, it upregulated the expression of insulin-like growth factor-1 and phosphoinositide-3 kinase, whereas the expression of ADAM-17 was downregulated. The expression of ADAM-17 is corroborated by the analysis of TIMP-3 content. In addition, the NSO significantly reduced blood glucose level, components of the lipid profile, oxidative stress parameters, serum insulin/insulin receptor ratio, and the tumor necrosis factor-α, confirming that NSO has an antidiabetic activity. Thus, the daily NSO treatment in our rat model indicates that NSO has a potential in the management of diabetes as well as improvement of insulin-induced signaling.

scholarly journals Maternal High Fat Diet-Induced Obesity Modifies Histone Binding and Expression of Oxtr in Offspring Hippocampus in a Sex-Specific Manner

2019 ◽  
Vol 20 (2) ◽  
pp. 329 ◽  
Author(s):  
Kelly Glendining ◽  
Christine Jasoni
Keyword(s):  
Gene Expression ◽  
Neurodevelopmental Disorders ◽  
High Fat Diet ◽  
Maternal Obesity ◽  
Transcriptional Start Site ◽  
Regulation Of Gene Expression ◽  
Female Offspring ◽  
High Fat ◽  
Histone Binding ◽  
Transcriptional Changes

Maternal obesity during pregnancy increases risk for neurodevelopmental disorders in offspring, although the underlying mechanisms remain unclear. Epigenetic deregulation associates with many neurodevelopmental disorders, and recent evidence indicates that maternal nutritional status can alter chromatin marks in the offspring brain. Thus, maternal obesity may disrupt epigenetic regulation of gene expression during offspring neurodevelopment. Using a C57BL/6 mouse model, we investigated whether maternal high fat diet (mHFD)-induced obesity alters the expression of genes previously implicated in the etiology of neurodevelopmental disorders within the Gestational Day 17.5 (GD 17.5) offspring hippocampus. We found significant two-fold upregulation of oxytocin receptor (Oxtr) mRNA in the hippocampus of male, but not female, GD 17.5 offspring from mHFD-induced obese dams (p < 0.05). To determine whether altered histone binding at the Oxtr gene promoter may underpin these transcriptional changes, we then performed chromatin immunoprecipitation (ChIP). Consistent with the Oxtr transcriptional changes, we observed increased binding of active histone mark H3K9Ac at the Oxtr transcriptional start site (TSS) in the hippocampus of mHFD male (p < 0.05), but not female, offspring. Together, these data indicate an increased vulnerability of male offspring to maternal obesity-induced changes in chromatin remodeling processes that regulate gene expression in the developing hippocampus, and contributes to our understanding of how early life nutrition affects the offspring brain epigenome.

scholarly journals Macronutrient balances and obesity: the role of diet and physical activity

1999 ◽  
Vol 2 (3a) ◽  
pp. 341-347 ◽  
Author(s):  
Arne Astrup
Keyword(s):  
Physical Activity ◽  
Weight Loss ◽  
Body Weight ◽  
Weight Gain ◽  
Physical Fitness ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Fat Oxidation ◽  
Fat Content ◽  
High Fat

AbstractObservational cross-sectional and longitudinal studies suggest that a high fat diet and physical inactivity are independent risk factors for weight gain and obesity. Mechanistic and intervention studies support that fat possesses a lower satiating power than carbohydrate and protein, and a diet low in fat therefore decreases energy intake. The effect of dietary fat on energy balance is enhanced in susceptible subjects, particularly in sedentary individuals with a genetic predisposition to obesity who consume a high fat diet.Dietary carbohydrate promotes its own oxidation by an insulin-mediated stimulation of glucose oxidation. In contrast, high fat meals do not increase fat oxidation acutely. A sedentary life-style and low physical fitness cause a low muscular fat oxidation capacity, and the consumption of a high fat diet by these individuals promotes fat storage in a synergistic fashion.Ad libitum low fat diets cause weight loss proportional to pre-treatment body weight in a dose-dependent way, i.e. weight loss is correlated positively to the reduction in dietary fat content. Increased physical activity prevents relapse after weight loss and studies have shown that those who keep up a higher level of physical activity are more successful in maintaining the reduced body weight. In conclusion, important interactions exist between genetic make up, dietary fat and physical fitness, so that a low fitness level and susceptible genes reduce muscular fat oxidation capacity which may decrease the tolerance of dietary fat. Increasing daily physical activity and reducing dietary fat content may be more effective when combined than when separate in preventing weight gain and obesity.

scholarly journals A Maternal High Fat Diet Leads to Sex-Specific Programming of Mechanical Properties in Supraspinatus Tendons of Adult Rat Offspring

2021 ◽  
Vol 8 ◽  
Author(s):  
Scott M. Bolam ◽  
Vidit V. Satokar ◽  
Subhajit Konar ◽  
Brendan Coleman ◽  
Andrew Paul Monk ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Maternal Diet ◽  
Biomechanical Properties ◽  
Female Offspring ◽  
Male Offspring ◽  
Chow Diet ◽  
Adult Offspring ◽  
High Fat ◽  
The Impact

Background: Over half of women of reproductive age are now overweight or obese. The impact of maternal high-fat diet (HFD) is emerging as an important factor in the development and health of musculoskeletal tissues in offspring, however there is a paucity of evidence examining its effects on tendon. Alterations in the early life environment during critical periods of tendon growth therefore have the potential to influence tendon health that cross the lifespan. We hypothesised that a maternal HFD would alter biomechanical, morphological and gene expression profiles of adult offspring rotator cuff tendon.Materials and Methods: Female Sprague-Dawley rats were randomly assigned to either: control diet (CD; 10% kcal or 43 mg/g from fat) or HFD (45% kcal or 235 mg/g from fat) 14 days prior to mating and throughout pregnancy and lactation. Eight female and male offspring from each maternal diet group were weaned onto a standard chow diet and then culled at postnatal day 100 for tissue collection. Supraspinatus tendons were used for mechanical testing and histological assessment (cellularity, fibre organisation, nuclei shape) and tail tendons were collected for gene expression analysis.Results: A maternal HFD increased the elasticity (Young's Modulus) in the supraspinatus tendon of male offspring. Female offspring tendon biomechanical properties were not affected by maternal HFD. Gene expression of SCX and COL1A1 were reduced in male and female offspring of maternal HFD, respectively. Despite this, tendon histological organisation were similar between maternal diet groups in both sexes.Conclusion: An obesogenic diet during pregnancy increased tendon elasticity in male, but not female, offspring. This is the first study to demonstrate that maternal diet can modulate the biomechanical properties of offspring tendon. A maternal HFD may be an important factor in regulating adult offspring tendon homeostasis that may predispose offspring to developing tendinopathies and adverse tendon outcomes in later life.

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