Amin Marashi’s Post

We recently published an article titled "IL-1β Inhibition Partially Negates the Beneficial Effects of Diet-Induced Atherosclerosis Regression in Mice" in ATVB. Thromboembolic events secondary to rupture or erosion of advanced atherosclerotic lesions is the global leading cause of death. However, we know little regarding the effects of reducing dietary lipids on the composition and stability of advanced atherosclerotic lesions, the mechanisms that regulate these processes, and what therapeutic approaches might augment the benefits of lipid lowering. We tested a hypothesis that IL-1β inhibition in mice with advanced atherosclerotic lesions in the setting of normalized lipids will have beneficial effects including increasing the cap thickness and multiple indices of plaque stability. Contrary to our hypothesis “IL-1β appears to be required for the maintenance of low-fat diet–induced reductions in plaque burden and increases in multiple indices of plaque stability”. Many people have an over-simplified view that any inflammatory response must be detrimental – i.e., inflammation is bad so global anti-inflammatory agents must be good. Be alert. https://lnkd.in/ew5FfsWn

🚀 Groundbreaking Research in Metabolic Regulation! 🚀 I am humbled, proud and thrilled to share with you the publication of our work entitled “Endothelial force sensing signals to parenchymal cells to regulate bile acid metabolism,” published in Science Advances https://lnkd.in/epUUwTTT We bring a new concept linking flow mediated force sensing at the endothelium to parenchymal regulation of lipid homeostasis. 🔍 Key Findings: 1/ Increased portal vein flow stimulates endothelial Piezo1, which down-regulates Cyp7a1, the crucial enzyme for bile acid synthesis. 2/ The coupling between endothelial force sensing and parenchymal regulation is mediated by nitric oxide. 3/ In the small intestine, endothelial Piezo1 deletion up regulates LDLr expression, and is associated with increased cholesterol elimination. 4/ Our findings suggest a novel connection between flow sensing and whole-body lipid metabolism. We suggest a basis where cardiovascular activity interacts with lipid homeostasis, potentially offering benefits in combating cardiovascular diseases that arise from hyperlipidaemia. Thank you to the great collaborators @UoL_LICAMM, University Of Leeds - School Of Medicine , Chew W Cheng Shaili Patel and Harry Konstantinou from Leeds Teaching Hospitals NHS Trust , Justine Bertrand-Michel Plateforme MetaToul-MetaboHUB from Inserm Toulouse, Professor Lee Roberts @Roberts_Lab, Bernadette Moore and Professor David Beech. University of Leeds School of Food Science & Nutrition, University of Leeds, UK. This work has been funded by British Heart Foundation and Wellcome Trust #Mechanobiology #Metabolism #LiverHealth #EndothelialCells #NitricOxide #BileAcid #Cholesterol #MetabolicDiseases #CardiovascularDiseases #ScienceAdvances

🔬 Ketogenic Diet & Beta-Hydroxybutyrate (BHB) Show Promise in Alzheimer’s Mouse Model 🧠 🐁 Key Highlights: 1️⃣ A ketogenic diet (KD) significantly rescued Long-Term Potentiation (LTP) in Alzheimer's mouse models, akin to wild-type levels, hinting at enhanced memory and synaptic functionality. 2️⃣ Beta-Hydroxybutyrate (BHB), identified as the ketogenic diet's active component, directly contributed to these improvements, showcasing its therapeutic potential. 3️⃣ The study found that the benefits of KD and BHB on cognitive function occurred independently of amyloid-β burden, offering a novel angle on addressing AD beyond traditional amyloid-targeting strategies. 4️⃣ Remarkably, the diet also mitigated brain inflammation and increased Brain-Derived Neurotrophic Factor (BDNF) levels in female mice, suggesting potential sex-specific therapeutic approaches. Really interesting! For more insights check out the paper: https://lnkd.in/dW3pG9R7 #alzheimersdisease #alzheimersresearch #invivo #ketogenicdiet #neuroplasticity  

Looking forward to presenting the results of our team's study on endoscopic ablation of the gastric fundus in adults with obesity at Digestive Disease Week® (DDW) this weekend. Thanks, Medscape, for highlighting the study. In our first-in-human trial, which targeted the "hunger hormone" ghrelin, participants experienced a significant decrease in hunger, appetite, and cravings, leading to a 7.7% body weight loss over six months. These findings underscore the potential of gastric fundus ablation as a viable alternative or complement to existing weight-loss medications and surgeries. "It's clear that we need every tool possible to address this because we know that obesity is not a matter of willpower. It's a disease." I'm honored to have led this research with my colleagues, Daniel Maselli, M.D. (Associate Director of Research and lead study author), Lauren Donnangelo, MD, D-ABOM (clinician investigator), and the entire research team at True You Weight Loss, and to see the positive impact it could have on patients' lives. https://lnkd.in/eDhjaE_s

What if improving metabolic health 🧬 could reduce cancer risks 🎗️and improve outcomes? (And NO it’s not just about weight loss ⚖️.)  This is an area where I see there is a role for the GLP-1 #weightloss drugs that are the topic of many conversations. Recent research shows GLP-1 receptor agonists don’t just aid weight management—they significantly improve metabolic health by targeting fat distribution and reducing harmful visceral fat. 🧬  While opinions on these medications may be deeply divided, their staying power is undeniable—making it crucial to understand their impact for the benefit of our patients. Here’s what the science reveals:  1️⃣ Visceral Fat Reduction: Users experienced a significant drop in visceral fat (-14.61 cm²), the dangerous fat linked to chronic inflammation, insulin resistance, and cardiovascular disease.   2️⃣ Stable Muscle Composition: Despite a modest reduction in lean mass (-1.02 kg), the muscle-to-fat ratio remained stable—ensuring metabolic improvements without compromising strength.   3️⃣ Metabolic Boosters: GLP-1 agonists enhance satiety, reduce ectopic fat (like liver fat), and improve insulin sensitivity, addressing the root causes of metabolic dysfunction.  🎯 Why This Matters:   Reducing visceral fat isn’t just about managing weight—it’s about combating systemic inflammation and lowering the risks associated with chronic illnesses like heart disease, diabetes, and even cancer.  For patients with a history of metabolic disease or conditions like cancer, this approach can deliver life-changing health benefits, especially when paired with interventions like resistance training and a nutrient-dense diet.  Let’s rethink how we approach metabolic health: less about the number on the scale and more about improving the quality of life at the cellular level.  Two important 🔑 factors 1. Resistance Strength Training - focused on muscle and power 2. Protein intake (ideally .8 - 1 g/lb ideal body weight) Both of these also improve function, energy, #immunesystem and other overall health and wellness goals! #MetabolicHealth #GLP1 #HealthcareInnovation #ChronicDisease #lifestylemedicine #exerciseoncology

Abdominal aortic aneurysms (AAAs) are a serious condition often linked to aging, with rupture leading to high mortality rates. Currently, there is no effective medical therapy to prevent AAA rupture. The C–C chemokine receptor type 2 (CCR2) pathway plays a critical role in inflammation and extracellular matrix degradation, both of which contribute to AAA formation and rupture. Researchers hypothesized that ketosis could modulate CCR2 and prevent the progression of AAA. In this study, male rats underwent AAA formation and were assigned to one of three interventions: a standard diet, a ketogenic diet (KD), or exogenous ketones (EKB). Rats receiving KD and EKB achieved a state of ketosis and demonstrated a significant reduction in AAA expansion and rupture rates. Rats that received a KD demonstrated the most notable effects. Key findings: 🔷 Reduced AAA expansion: Rats on the ketogenic diet showed a 42% decrease in AAA diameter after 2 weeks compared to controls. 🔷 Lower rupture rates: Rats on the ketogenic diet showed a 67% reduction in rupture rate. 🔷 CCR2 downregulation: Ketosis reduced the expression of CCR2 in the aortic wall, leading to lower inflammation and extracellular matrix degradation. CCR2-knockout mice showed a similar protective effect. 🔷 Improved matrix metalloproteinase (MMP) balance: Active MMP9, which promotes AAA formation, was reduced, while the stabilizing MMP9/TIMP1 complex increased, preserving the aortic wall structure. These results suggest that ketosis could serve as a potential therapeutic approach for stabilizing AAAs and reducing the risk of rupture. Further clinical studies are needed to evaluate its efficacy in humans — Sastriques-Dunlop et al. Ketosis prevents abdominal aortic aneurysm rupture through C–C chemokine receptor type 2 downregulation and enhanced extracellular matrix balance. Sci Rep. 2024;14(1):1438. doi: 10.1038/s41598-024-51996-7. 📌 Link to study: https://lnkd.in/gN8UPmem 📌 Find more research summaries on our website: https://lnkd.in/gKeXEcEN #Keto #KetoDiet #Research

In this recently published study, researchers investigated whether sodium #butyrate could reduce sympathetic activation in a rat model of heart failure. Rats (220‒250 g) were assigned to a control group or treated with sodium butyrate for 8 weeks after inducing heart failure. It was found that sodium butyrate improved cardiac function (mean ejection fraction increased from 22.6%±4.8% to 38.3%±5.3%) and decreased sympathetic activation (renal sympathetic nerve activity decreased from 36.3%±7.9% to 23.9%±7.6%) vs. untreated rats. Sodium butyrate also reduced plasma and CSF levels of norepinephrine. It was also observed that treatment with sodium butyrate decreased microglia-mediated #inflammation in the paraventricular nucleus. In addition, sodium butyrate improved some measures of intestinal barrier function such as increasing the expression of some tight junction proteins and decreased circulating LPS binding protein. It would be interesting to see if other sources of butyrate used in #animalnutrition such as butyric glycerides would lead to similar findings.

📃Scientific paper: Feeding High-Fat Diet Accelerates Development of Peripheral and Central Insulin Resistance and Inflammation and Worsens AD-like Pathology in APP/PS1 Mice Abstract: Alzheimer's disease (AD) is a progressive brain disorder characterized by extracellular amyloid-β (Aβ) plaques, intracellular neurofibrillary tangles formed by hyperphosphorylated Tau protein and neuroinflammation. Previous research has shown that obesity and type 2 diabetes mellitus, underlined by insulin resistance (IR), are risk factors for neurodegenerative disorders. In this study, obesity-induced peripheral and central IR and inflammation were studied in relation to AD-like pathology in the brains and periphery of APP/PS1 mice, a model of Aβ pathology, fed a high-fat diet (HFD). APP/PS1 mice and their wild-type controls fed either a standard diet or HFD were characterized at the ages of 3, 6 and 10 months by metabolic parameters related to obesity via mass spectroscopy, nuclear magnetic resonance, immunoblotting and immunohistochemistry to quantify how obesity affected AD pathology. The HFD induced substantial peripheral IR leading to central IR. APP/PS1-fed HFD mice had more pronounced IR, glucose intolerance and liver steatosis than their WT controls. The HFD worsened Aβ pathology in the hippocampi of APP/PS1 mice and significantly supported both peripheral and central inflammation. This study reveals a deleterious effect of obesity-related mild peripheral inflammation and prediabetes on the development of Aβ and Tau pathology and neuroinflammation in APP/PS1 mice. Continued on ES/IODE ➡️ https://etcse.fr/lO2a ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you. #alzheimer #science #health

📃Scientific paper: Feeding High-Fat Diet Accelerates Development of Peripheral and Central Insulin Resistance and Inflammation and Worsens AD-like Pathology in APP/PS1 Mice Abstract: Alzheimer's disease (AD) is a progressive brain disorder characterized by extracellular amyloid-β (Aβ) plaques, intracellular neurofibrillary tangles formed by hyperphosphorylated Tau protein and neuroinflammation. Previous research has shown that obesity and type 2 diabetes mellitus, underlined by insulin resistance (IR), are risk factors for neurodegenerative disorders. In this study, obesity-induced peripheral and central IR and inflammation were studied in relation to AD-like pathology in the brains and periphery of APP/PS1 mice, a model of Aβ pathology, fed a high-fat diet (HFD). APP/PS1 mice and their wild-type controls fed either a standard diet or HFD were characterized at the ages of 3, 6 and 10 months by metabolic parameters related to obesity via mass spectroscopy, nuclear magnetic resonance, immunoblotting and immunohistochemistry to quantify how obesity affected AD pathology. The HFD induced substantial peripheral IR leading to central IR. APP/PS1-fed HFD mice had more pronounced IR, glucose intolerance and liver steatosis than their WT controls. The HFD worsened Aβ pathology in the hippocampi of APP/PS1 mice and significantly supported both peripheral and central inflammation. This study reveals a deleterious effect of obesity-related mild peripheral inflammation and prediabetes on the development of Aβ and Tau pathology and neuroinflammation in APP/PS1 mice. Continued on ES/IODE ➡️ https://etcse.fr/lO2a ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you. #alzheimer #science #health

📃Scientific paper: Feeding High-Fat Diet Accelerates Development of Peripheral and Central Insulin Resistance and Inflammation and Worsens AD-like Pathology in APP/PS1 Mice Abstract: Alzheimer's disease (AD) is a progressive brain disorder characterized by extracellular amyloid-β (Aβ) plaques, intracellular neurofibrillary tangles formed by hyperphosphorylated Tau protein and neuroinflammation. Previous research has shown that obesity and type 2 diabetes mellitus, underlined by insulin resistance (IR), are risk factors for neurodegenerative disorders. In this study, obesity-induced peripheral and central IR and inflammation were studied in relation to AD-like pathology in the brains and periphery of APP/PS1 mice, a model of Aβ pathology, fed a high-fat diet (HFD). APP/PS1 mice and their wild-type controls fed either a standard diet or HFD were characterized at the ages of 3, 6 and 10 months by metabolic parameters related to obesity via mass spectroscopy, nuclear magnetic resonance, immunoblotting and immunohistochemistry to quantify how obesity affected AD pathology. The HFD induced substantial peripheral IR leading to central IR. APP/PS1-fed HFD mice had more pronounced IR, glucose intolerance and liver steatosis than their WT controls. The HFD worsened Aβ pathology in the hippocampi of APP/PS1 mice and significantly supported both peripheral and central inflammation. This study reveals a deleterious effect of obesity-related mild peripheral inflammation and prediabetes on the development of Aβ and Tau pathology and neuroinflammation in APP/PS1 mice. Continued on ES/IODE ➡️ https://etcse.fr/lO2a ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you. #alzheimer #science #health