Abstract 76: Intra-Placental Gene Transfer of Human Insulin-Like Growth Factor-1 Prevents Obesity in an Intra- Uterine Growth Restricted Model Exposed to High Fat Diet Postnatally

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Khaled R Omar ◽  
Helen Jones ◽  
Swathi Balaji ◽  
Young Nam ◽  
Kitcheol Kil ◽  
...  
Keyword(s):  
Body Weight ◽  
Birth Weight ◽  
Gene Transfer ◽  
Environmental Stress ◽  
High Fat Diet ◽  
Adult Onset ◽  
High Fat ◽  
Fasting Serum ◽  
Artery Ligation ◽  
Serum Leptin

We have shown that mesenteric uterine artery ligation in mice significantly reduces fetal birth weight (IUGR) and increases risk of adult onset of hypertension and obesity, which are all reversed by adenoviral mediated hIGF1 (Ad hIGF1) intraplacental gene transfer. We hypothesized that intraplacental Ad hIGF1 in IUGR mice prevents adult onset of obesity even when challenged with environmental stress as fat diet. Laparotomy was done at day 18 on pregnant C57BL/6J mice and divided into 3 groups (n= 16). Control: Sham operated; IUGR: birth weight <10% for gestational age; Treated: IUGR+IGF-1. Pups were delivered on day 20, cross fostered to CD1 mice, sorted by gender at 4 weeks. At 8 weeks, high fat diet (45% fat) was introduced and mice were followed up to 24 weeks. Body weight, fat pad, fasting serum leptin and food consumption were measured. Data analyzed by Chi-square or ANOVA and stratified by sex Compared to sham, IUGR significantly decreases birth weight, which is restored to normal in IUGR+IGF-1(1.12± .1 vs 0.9± .1 vs 1.09± .1 g, p=0.001). Mean body weight differences among the groups persist till 8 weeks. By 14 weeks, male IUGR mice had significant weight gain(obese) compared to sham and treatment groups (fig A). Same trend was seen in female IUGR at 18 weeks. Total fad pad weights were significantly higher in IUGR compared to SHAM, restored to normal in IUGR+IGF-1 (fig B). Compared to sham, IUGR significantly increases fasting serum leptin, restored to normal in IUGR+IGF-1 (2.4±0.2 vs 7.9±1.5 vs 3.4±0.4 pg/ug, p= .01) Our results demonstrate that intraplacental gene transfer with Ad-hIGF-1 reprograms the IUGR fetus and attenuates the risk of adult onset of obesity under environmental stress

Abstract 192: Intra-Placental Gene Transfer of Human Insulin-Like Growth Factor-1 Reprograms Fetal Predisposition to Obesity in Intra-uterine Growth Restriction

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Khaled R Omar ◽  
Helen Jones ◽  
Swathi Balaji ◽  
Young Nam ◽  
Kitcheol Kil ◽  
...  
Keyword(s):  
Body Weight ◽  
Birth Weight ◽  
Gene Transfer ◽  
Food Consumption ◽  
Mice Model ◽  
Fasting Serum ◽  
Chi Square ◽  
Serum Leptin ◽  
Increased Risk ◽  
Fetal Reprogramming

We have shown that intra placental adenoviral mediated gene transfer of (Ad hIGF1) corrects birth weight in a new surgical mouse IUGR model. Evidence shows that IUGR offspring are predisposed to increased risk of adult diseases. We hypothesized that intraplacental Ad hIGF1 not only restores birth weight in this IUGR model but prevents adult onset obesity through fetal reprogramming Laparotomy was done at day 18 on time pregnant C57BL/6J mice, divided into 3 groups. Control: Sham operated; IUGR: birth weight <10% for gestational age; Treated: IUGR+IGF1; n= 16. Pups were delivered on day 20, cross fostered to surrogate CD1 mice, sorted by gender at 4 weeks and followed up to 24 weeks. Body weight, fat pad weight, fasting serum leptin and food consumption were measured. Data analyzed by Chi-square or ANOVA Compared to SHAM, IUGR significantly reduced birth weight, restored to normal in IUGR+IGF-1 (1.12± .1vs 0.9± .1 vs 1.09± .1 g, p= .001). At 8 weeks, IUGR achieved mean body weight equivalent to SHAM and IUGR+IGF-1. By week 21, regardless of sex, IUGR significantly increased weight (obesity) compared to sham and IUGR+IGF-1 (fig A). Total fad pad weights were significantly higher in IUGR compared to SHAM but were restored to normal in IUGR+IGF1 (fig B). IUGR significantly increased fasting serum leptin, compared to Sham and restored to normal in IUGR+IGF1 ( .6± .4vs 5.7± 1.1 vs .8± .4 pg/ug, p= .01). No difference in food consumption amongst the groups Intra placental gene transfer of Ad hIGF1 corrects birth weight in IUGR mice model and attenuates the risk of postnatal obesity, This support the concept that in utero reprogramming of fetal predisposition to obesity is a novel approch to treatment of IUGR.

scholarly journals Characterizing the Retinal Phenotype in the High-Fat Diet and Western Diet Mouse Models of Prediabetes

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 464 ◽  
Author(s):  
Bright Asare-Bediako ◽  
Sunil Noothi ◽  
Sergio Li Calzi ◽  
Baskaran Athmanathan ◽  
Cristiano Vieira ◽  
...  
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Fundus Photography ◽  
Vascular Density ◽  
Sensitivity Index ◽  
High Fat ◽  
Permeability Studies ◽  
Induced Changes ◽  
Acellular Capillaries

We sought to delineate the retinal features associated with the high-fat diet (HFD) mouse, a widely used model of obesity. C57BL/6 mice were fed either a high-fat (60% fat; HFD) or low-fat (10% fat; LFD) diet for up to 12 months. The effect of HFD on body weight and insulin resistance were measured. The retina was assessed by electroretinogram (ERG), fundus photography, permeability studies, and trypsin digests for enumeration of acellular capillaries. The HFD cohort experienced hypercholesterolemia when compared to the LFD cohort, but not hyperglycemia. HFD mice developed a higher body weight (60.33 g vs. 30.17g, p < 0.0001) as well as a reduced insulin sensitivity index (9.418 vs. 62.01, p = 0.0002) compared to LFD controls. At 6 months, retinal functional testing demonstrated a reduction in a-wave and b-wave amplitudes. At 12 months, mice on HFD showed evidence of increased retinal nerve infarcts and vascular leakage, reduced vascular density, but no increase in number of acellular capillaries compared to LFD mice. In conclusion, the HFD mouse is a useful model for examining the effect of prediabetes and hypercholesterolemia on the retina. The HFD-induced changes appear to occur slower than those observed in type 2 diabetes (T2D) models but are consistent with other retinopathy models, showing neural damage prior to vascular changes.

scholarly journals Protective Effects of Polyphenol Enriched Complex Plants Extract on Metabolic Dysfunctions Associated with Obesity and Related Nonalcoholic Fatty Liver Diseases in High Fat Diet-Induced C57BL/6 Mice

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 302
Author(s):  
Ahtesham Hussain ◽  
Jin Sook Cho ◽  
Jong-Seok Kim ◽  
Young Ik Lee
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Mouse Model ◽  
High Fat Diet ◽  
Liver Diseases ◽  
Liver Weight ◽  
Control Group ◽  
High Fat ◽  
Herbal Formulation ◽  
Plants Extract

Background: Currently, obesity is a global health challenge due to its increasing prevalence and associated health risk. It is associated with various metabolic diseases, including diabetes, hypertension, cardiovascular disease, stroke, certain forms of cancer, and non-alcoholic liver diseases (NAFLD). Objective: The aim of this study to evaluate the effects of polyphenol enriched herbal complex (Rubus crataegifolius/ellagic acid, Crataegus pinnatifida Bunge/vitexin, chlorogenic acid, Cinnamomum cassiaa/cinnamic acid) on obesity and obesity induced NAFLD in the high-fat diet (HFD)-induced obese mouse model. Methods: Obesity was induced in male C57BL/6 mice using HFD. After 8 weeks, the mice were treated with HFD+ plants extract for 8 weeks. Body weight, food intake weekly, and blood sugar level were measured. After sacrifice, changes in the treated group’s liver weight, fat weight, serum biochemical parameters, hormone levels, and enzyme levels were measured. For histological analysis, tissues were stained with hematoxylin-eosin (H&E) and Oil Red-O. Results: Our results showed that the herbal complex ameliorated body weight and liver weight gain, and decreased total body fat in HFD-fed animals. Post prandial blood glucose (PBG) and fasting blood glucose (FBG) were lower in the herbal complex-treated group than in the HFD control group. Additionally, herbal formulation treatment significantly increased HDL levels in serum and decreased TC, TG, AST, ALT, deposition of fat droplets in the liver, and intima media thickness (IMT) in the aorta. Herbal complex increased serum adiponectin and decreased serum leptin. Herbal complex also increased carnitine palmityl transferase (CPT) activity and significantly decreased enzyme activity of beta-hydroxy beta methyl glutamyl-CoA (HMG-CoA) reductase, and fatty acid synthase (FAS). Conclusions: The results of this study demonstrated that the herbal complex is an effective herbal formulation in the attenuation of obesity and obesity-induced metabolic dysfunction including NAFLD in HFD-induced mouse model.

scholarly journals Intermittent Fasting Ameliorated High-Fat Diet-Induced Memory Impairment in Rats via Reducing Oxidative Stress and Glial Fibrillary Acidic Protein Expression in Brain

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 10
Author(s):  
Suzan M. Hazzaa ◽  
Mabrouk A. Abd Eldaim ◽  
Amira A. Fouda ◽  
Asmaa Shams El Dein Mohamed ◽  
Mohamed Mohamed Soliman ◽  
...  
Keyword(s):  
Body Weight ◽  
Glial Fibrillary Acidic Protein ◽  
Brain Tissue ◽  
High Fat Diet ◽  
Serum Lipids ◽  
Memory Performance ◽  
Granular Cell ◽  
Intermittent Fasting ◽  
High Fat ◽  
Cell Layers

Intermittent fasting (IF) plays an important role in the protection against metabolic syndrome-induced memory defects. This study aimed to assess the protective effects of both prophylactic and curative IF against high-fat diet (HFD)-induced memory defects in rats. The control group received a normal diet; the second group received a HFD; the third group was fed a HFD for 12 weeks and subjected to IF during the last four weeks (curative IF); the fourth group was fed a HFD and subjected to IF simultaneously (prophylactic IF). A high-fat diet significantly increased body weight, serum lipids levels, malondialdehyde (MDA) concentration, glial fibrillary acidic protein (GFAP) and H score in brain tissue and altered memory performance. In addition, it significantly decreased reduced glutathione (GSH) concentration in brain tissue and viability and thickness of pyramidal and hippocampus granular cell layers. However, both types of IF significantly decreased body weight, serum lipids, GFAP protein expression and H score and MDA concentration in brain tissue, and improved memory performance, while it significantly increased GSH concentration in brain tissue, viability, and thickness of pyramidal and granular cell layers of the hippocampus. This study indicated that IF ameliorated HFD-induced memory disturbance and brain tissue damage and the prophylactic IF was more potent than curative IF.

Potential mechanisms of improvement in body weight, metabolic profile, and liver metabolism by honey in rats on a high fat diet

2020 ◽  
Vol 14 ◽  
pp. 100227
Author(s):  
Atia Gohar ◽  
Muhammad Shakeel ◽  
Richard. L. Atkinson ◽  
Darakhshan J. Haleem
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Metabolic Profile ◽  
Liver Metabolism ◽  
High Fat

scholarly journals Maternal high-fat diet induces metabolic stress response disorders in offspring hypothalamus

2017 ◽  
Vol 59 (1) ◽  
pp. 81-92 ◽  
Author(s):  
Long The Nguyen ◽  
Sonia Saad ◽  
Yi Tan ◽  
Carol Pollock ◽  
Hui Chen
Keyword(s):  
Endoplasmic Reticulum ◽  
Body Weight ◽  
Er Stress ◽  
High Fat Diet ◽  
Maternal Obesity ◽  
Mrna Level ◽  
Metabolic Stress ◽  
High Fat ◽  
Chemical Chaperone ◽  
Protein Levels

Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect. In this study, we show that offspring born to high-fat diet-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning. Hypothalamic mRNA level of the orexigenic neuropeptide Y (NPY) was increased, while the levels of the anorexigenic pro-opiomelanocortin (POMC), NPY1 receptor (NPY1R) and melanocortin-4 receptor (MC4R) were significantly downregulated. In association, the expression of unfolded protein response (UPR) markers including glucose-regulated protein (GRP)94 and endoplasmic reticulum DNA J domain-containing protein (Erdj)4 was reduced. By contrast, protein levels of autophagy-related genes Atg5 and Atg7, as well as mitophagy marker Parkin, were slightly increased. The administration of 4-phenyl butyrate (PBA), a chemical chaperone of protein folding and UPR activator, in the offspring from postnatal day 4 significantly reduced their body weight, fat deposition, which were in association with increased activating transcription factor (ATF)4, immunoglobulin-binding protein (BiP) and Erdj4 mRNA as well as reduced Parkin, PTEN-induced putative kinase (PINK)1 and dynamin-related protein (Drp)1 protein expression levels. These results suggest that hypothalamic ER stress and mitophagy are among the regulatory factors of offspring metabolic changes due to maternal obesity.

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