Effects of Incretin-Based Therapies on Neuro-Cardiovascular Dynamic Changes Induced by High Fat Diet in Rats

The sensitivity of baroreflex control of heart rate is depressed in subjects with obesity hypertension, which increases the risk for cardiac arrhythmias. The mechanisms are not fully known, and there are no therapies to improve this dysfunction. To determine the cardiovascular dynamic effects of progressive increases in body weight leading to obesity and hypertension in dogs fed a high-fat diet, 24-h continuous recordings of spontaneous fluctuations in blood pressure and heart rate were analyzed in the time and frequency domains. Furthermore, we investigated whether autonomic mechanisms stimulated by chronic baroreflex activation and renal denervation—current therapies in patients with resistant hypertension, who are commonly obese—restore cardiovascular dynamic control. Increases in body weight to ∼150% of control led to a gradual increase in mean arterial pressure to 17 ± 3 mmHg above control (100 ± 2 mmHg) after 4 wk on the high-fat diet. In contrast to the gradual increase in arterial pressure, tachycardia, attenuated chronotropic baroreflex responses, and reduced heart rate variability were manifest within 1–4 days on high-fat intake, reaching 130 ± 4 beats per minute (bpm) (control = 86 ± 3 bpm) and ∼45% and <20%, respectively, of control levels. Subsequently, both baroreflex activation and renal denervation abolished the hypertension. However, only baroreflex activation effectively attenuated the tachycardia and restored cardiac baroreflex sensitivity and heart rate variability. These findings suggest that baroreflex activation therapy may reduce the risk factors for cardiac arrhythmias as well as lower arterial pressure.

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The Effect of a Sustained High-Fat Diet on the Metabolism of White and Brown Adipose Tissue and Its Impact on Insulin Resistance: A Selected Time Point Cross-Sectional Study

International Journal of Molecular Sciences ◽

10.3390/ijms222413639 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13639

Author(s):

Babu Raja Maharjan ◽

Susan V. McLennan ◽

Christine Yee ◽

Stephen M. Twigg ◽

Paul F. Williams

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

High Fat Diet ◽

Liver Fat ◽

Lipid Deposition ◽

High Fat ◽

Dynamic Changes ◽

Gene Markers ◽

Fat Depots ◽

Brown Adipose

(1) Background: studies on the long-term dynamic changes in fat depot metabolism in response to a high-fat diet (HFD) on hepatic lipid deposition and insulin resistance are sparse. This study investigated the dynamic changes produced by HFD and the production of dysfunctional fat depots on insulin resistance and liver lipid metabolism. (2) Methods: mice fed a chow or HFD (45% kcal fat) diet had three fat depots, liver, and blood collected at 6, 10, 20, and 30 weeks. Anthropometric changes and gene markers for adipogenesis, thermogenesis, ECM remodeling, inflammation, and tissue insulin resistance were measured. (3) Results: early responses to the HFD were increased body weight, minor deposition of lipid in liver, increased adipocyte size, and adipogenesis. Later changes were dysfunctional adipose depots, increased liver fat, insulin resistance (shown by changes in ITT) accompanied by increased inflammatory markers, increased fibrosis (fibrosis > 2-fold, p < 0.05 from week 6), and the presence of crown cells in white fat depots. Later, changes did not increase thermogenic markers in response to the increased calories and decreased UCP1 and PRDM16 proteins in WAT. (4) Conclusions: HFD feeding initially increased adipocyte diameter and number, but later changes caused adipose depots to become dysfunctional, restricting adipose tissue expansion, changing the brown/beige ratios in adipose depots, and causing ectopic lipid deposition and insulin resistance.

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Dynamic changes of serotonin levels induces depression-like behaviour in mice with high-fat diet

10.21203/rs.3.rs-1178329/v1 ◽

2021 ◽

Author(s):

Yan Chen ◽

Lifang Chen ◽

Tingting Gong ◽

Haotian Liu ◽

Shengfeng Wang ◽

...

Keyword(s):

Depressive Symptoms ◽

Mental Disorders ◽

High Fat Diet ◽

Treatment Options ◽

Treatment Strategies ◽

High Fat ◽

First Line ◽

Dynamic Changes

Abstract Introduction of SSRI as the first-line pharmacotherapy options for depression, which purpose is to increase the concentrations of 5-HT in brain and help reduce depressive symptoms. However, there are still many limitations to the effectiveness of these treatment strategies, 30-40% of patients do not respond to treatment at all, and even suicide occurs. In the present study, we revealed that increasing brain 5-HT concentration is not the best treatment options. When we injected sufficient amounts of 5-HT into the lateral ventricular region of mice, it actually caused depression-like behavior in the animals. The second study on high-fat fed induces depressive symptoms in mice demonstrated that 5-HT concentration in brain showed a tendency to increase first and then decrease. Both experiments indicated that if SSRI are administrated to the patient in the acute phases of depression, it may lead to exacerbation of mental disorders or suicidal tendencies.

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Abstract 182: Quantitative Proteomics Reveals Dynamic Changes of Plasma Proteome in APOE-Deficient Mice at Four Phases of Atherosclerosis

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.33.suppl_1.a182 ◽

2013 ◽

Vol 33 (suppl_1) ◽

Author(s):

Linhong Jing ◽

Zhu-qiu Jin ◽

Wei Xie ◽

Shuaipeng J Zhang

Keyword(s):

High Fat Diet ◽

Plasma Proteins ◽

Immune Modulation ◽

Complement C3 ◽

Plasma Proteome ◽

High Fat ◽

Dynamic Changes ◽

Proteome Changes ◽

Disease Stages ◽

Deficient Mice

Introduction To understand the mechanism for atherosclerotic disease at molecular level, we analyzed the dynamic changes of plasma proteome in mice at four different disease stages vs. control based on hypothesis that a panel of plasma proteins might associate with the progression of atherosclerosis. Methods Male APOE knockout (-/-) mice were fed with high fat diet and euthanized at 8, 12, 18 or 24 weeks of age, representing the early, intermediate, moderate and later stages of disease. Age-matched male wild type mice fed with high fat diet served as controls. At the time of euthanasia, aorta and plasma were collected. A mass spectrometry-based proteomics approach was employed to simultaneously quantify proteins in eight pooled samples. Results Image analysis of lesions in aortas (stained with Sudan IV) from 40 APOE -/- mice (10 mice at each time point) demonstrated the development of four different phases of disease (Fig.). No lesion was observed in the control mice. We have identified 57 dysregulated proteins (e.g., fibrinogen beta and gamma chains, complement C3, C4B, C9, apolipoproteins, etc.) at four disease stages. These protein’s expression levels, biological functions (e.g. immune modulation and inflammation), and pathways (e.g., complement and cogulation cascades) provide a better understanding of the basic molecular processes in atherosclerosis. Conclusions 1) Proteomics analysis of plasma proteome changes at different stages of APOE-deficient mice facilitated the mechanistic studies of atherosclerosis. 2) A panel of plasma proteins was identified as potential “signatures” of atherosclerosis which may help early diagnosis and therapeutic intervention.

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Dynamic changes in basal lamina fenestrations in rat intestinal villous epithelium under high-fat diet condition

Biomedical Research ◽

10.2220/biomedres.40.57 ◽

2019 ◽

Vol 40 (2) ◽

pp. 57-66

Author(s):

Keisuke MORITA ◽

Rie AZUMI ◽

Masatoshi SATO ◽

Yusuke MIZUTANI ◽

Manabu HAYATSU ◽

...

Keyword(s):

Basal Lamina ◽

High Fat Diet ◽

High Fat ◽

Dynamic Changes

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Abstract # P-20: 11b-Hydroxysteroid Dehydrogenase 1 Regulation in High Fat Diet Induced Insulin Resistant Rats and Rats Treated with Sutherlandia Frutescens

Endocrine Practice ◽

10.1016/s1530-891x(20)43833-9 ◽

2016 ◽

Vol 22 ◽

pp. 23

Author(s):

Ngozi F. Nnolum-Orji ◽

Saartjie Roux ◽

Janine Mackenzie ◽

Disang Lekutlane

Keyword(s):

High Fat Diet ◽

Hydroxysteroid Dehydrogenase ◽

High Fat ◽

Insulin Resistant ◽

Sutherlandia Frutescens

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Effects of Maternal Flaxseed Supplementation on Female Offspring of Diabetic Rats in Serum Concentration of Glucose, Insulin, and Thyroid Hormones

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000259 ◽

2019 ◽

Vol 89 (1-2) ◽

pp. 45-54

Author(s):

Akemi Suzuki ◽

André Manoel Correia-Santos ◽

Gabriela Câmara Vicente ◽

Luiz Guillermo Coca Velarde ◽

Gilson Teles Boaventura

Keyword(s):

Thyroid Hormones ◽

High Fat Diet ◽

Female Offspring ◽

Flaxseed Oil ◽

Diabetic Rats ◽

High Fat ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Flaxseed Flour ◽

Maternal Consumption

Abstract. Objective: This study aimed to evaluate the effect of maternal consumption of flaxseed flour and oil on serum concentrations of glucose, insulin, and thyroid hormones of the adult female offspring of diabetic rats. Methods: Wistar rats were induced to diabetes by a high-fat diet (60%) and streptozotocin (35 mg/kg). Rats were mated and once pregnancy was confirmed, were divided into the following groups: Control Group (CG): casein-based diet; High-fat Group (HG): high-fat diet (49%); High-fat Flaxseed Group (HFG): high-fat diet supplemented with 25% flaxseed flour; High-fat Flaxseed Oil group (HOG): high-fat diet, where soya oil was replaced with flaxseed oil. After weaning, female pups (n = 6) from each group were separated, received a commercial rat diet and were sacrificed after 180 days. Serum insulin concentrations were determined by ELISA, the levels of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) were determined by chemiluminescence. Results: There was a significant reduction in body weight at weaning in HG (−31%), HFG (−33%) and HOG (44%) compared to CG (p = 0.002), which became similar by the end of 180 days. Blood glucose levels were reduced in HFG (−10%, p = 0.044) when compared to CG, and there was no significant difference between groups in relation to insulin, T3, T4, and TSH after 180 days. Conclusions: Maternal severe hyperglycemia during pregnancy and lactation resulted in a microsomal offspring. Maternal consumption of flaxseed reduces blood glucose levels in adult offspring without significant effects on insulin levels and thyroid hormones.

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