Mass General Research Institute’s Post

Could the microbiota hold the key to revolutionizing hypertension treatment? Bina Joe PhD, FAHA, FAPS, ISHF and her team from the The University of Toledo College of Medicine and Life Sciences revealed a significant link between gut dysbiosis and hypertension, shedding light on how alterations in gut microbiota can elevate blood pressure. Key findings include the role of microbial metabolites like Short-chain fatty acids (SCFAs) in regulating blood pressure, bidirectional communication between the gut microbiota and the immune system, and the impact of abiotic factors such as circadian rhythms and diet. Advanced tools like metagenomics, AI, germ-free models, and CRISPR-Cas9 gene editing are driving investigations into personalized treatment approaches for hypertension. 🔗 Read more: https://lnkd.in/dU5YZJcS #TargetingMicrobiota2024 this October in Malta will keep you updated with the latest advance in the microbiota field in health and in disease. 🌐 Visit Conference Website: https://lnkd.in/dFTZBQSK #InternationalSocietyofMicrobiota #TargetingMicrobiota #microbiota #microbiome #gastrointestinalhealth

Researchers at the Universitätsklinikum Bonn (Germany) have identified a pivotal #protein known as EPAC1, which is essential for enhancing brown #fat cells’ activity. Brown fat is crucial in storing energy and utilizing it to maintain body temperature. By generating heat through #thermogenesis, brown fat contributes to #calorie burning while also playing a role in regulating #glucose and fat metabolism. Notably, brown fat cells offer additional protective benefits against #cardiovasculardiseases. In adults, brown fat is predominantly found around the neck, kidneys, adrenal glands, heart (aorta), and chest (mediastinum).   The team’s goal was to use EPAC1 as a target for developing medicines that support weight loss. #Obesity, characterized by an excess of white fat, is made worse by calorie-rich diets, which lead to energy storage in white fat, making it challenging to lose weight. The body also tends to conserve energy in response to #weightloss, explaining why low-calorie diets don’t often work long-term.   Brown fat cells are particularly active in newborns, helping them cope with exposure to cold temperatures. However, adults typically have minimal brown fat, primarily found in young and slim folks. The research team wanted to understand how to increase brown fat mass while reducing the more problematic white fat.   The study focused on a signaling pathway called cAMP in fat metabolism. They identified the EPAC1 protein as a critical player in brown fat growth. Notably, EPAC1 increased the formation of brown fat cells within white fat deposits, known as “beige” cells. The team confirmed the presence of this signaling pathway in human fat cells and verified the function of EPAC1 in human organoids, which are organ-like structures serving as a model for brown fat.   The researchers also discovered that a non-functional human EPAC1 gene variant is associated with an increased body mass index (#BMI). The researchers concluded that EPAC1 is an attractive target for increasing brown fat mass and energy expenditure. With the global rise in obesity, the team hopes to develop innovative therapies to help individuals combat #metabolicdiseases. Nature Portfolio   https://lnkd.in/e4_BJFXY

A recent paper by Professor Simon Bekker-Jensen's team from the Center for Healthy Aging at the Københavns Universitet - University of Copenhagen reveals new insights into potential #metabolic signaling pathways. The authors have identified a mechanism that connects reactive oxygen species (#ROS), a protein called ZAKα, and resulting changes in ribosome function. The research highlights how ROS-induced ribosomal impairment serves as a physiological activation signal for ZAKα, contributing to metabolic adaptation in conditions like #obesity and #aging. These findings present ZAKα kinase as a promising target for #drugdevelopment in metabolic conditions such as #nonalcoholic steatohepatitis, #hypertension, and #dyslipidemia. Read on: https://lnkd.in/grycSUc2 #research #metabolicdisease #signalingpathway #biotech #innovation #disease #mousemodels #breakthrough

【Medicine/Health】 Unraveling the Role of Macrophages in Regulating Inflammatory Lipids during Acute Kidney Injury Lipid mediators (LMs), which are physiologically active lipids, play a critical role in promoting and suppressing acute inflammation. This study conducted by researchers at the University of Tsukuba elucidates the molecular mechanisms by which macrophages, responsible for LM production, transition LMs from a pro-inflammatory to a pro-resolving state during acute kidney injury (AKI). Read more details here; https://lnkd.in/gKKpKQ7m Original Paper; https://lnkd.in/gZFmp4TP

Exciting News! 🎉 Our Latest Review Article Published in International Journal of Molecular Sciences! https://lnkd.in/eJx8UeBt Here we delve into the world of fatty acid metabolism, gathering valuable information that could reshape our understanding of this key energy source for cardiac function. 🔍 Abstract: This comprehensive review explores the critical role of fatty acid (FA) metabolism in cardiac diseases, particularly heart failure (HF), and the implications for therapeutic strategies. The heart’s reliance on ATP, primarily sourced from mitochondrial oxidative metabolism, underscores the significance of metabolic flexibility, with fatty acid oxidation (FAO) being a dominant source. In HF, metabolic shifts occur with an altered FA uptake and FAO, impacting mitochondrial function and contributing to disease progression. Conditions like obesity and diabetes also lead to metabolic disturbances, resulting in cardiomyopathy marked by an over-reliance on FAO, mitochondrial dysfunction, and lipotoxicity. Therapeutic approaches targeting FA metabolism in cardiac diseases have evolved, focusing on inhibiting or stimulating FAO to optimize cardiac energetics. Strategies include using CPT1A inhibitors, using PPARα agonists, and enhancing mitochondrial biogenesis and function. However, the effectiveness varies, reflecting the complexity of metabolic remodeling in HF. Hence, treatment strategies should be individualized, considering that cardiac energy metabolism is intricate and tightly regulated. The therapeutic aim is to optimize overall metabolic function, recognizing the pivotal role of FAs and the need for further research to develop effective therapies, with promising new approaches targeting mitochondrial oxidative metabolism and FAO that improve cardiac function. #IJMS #UCSanDiego

A recent study conducted by Prof. Ana Domingos's team at University of Oxford identified a group of sympathetic peripheral cells (#SPCs) expressing IL-33, which are LepR+ cells. These cells can wrap around nerve bundles, promote adaptive thermogenesis by preventing #inflammation. This study demonstrated that LepR+IL-33+ SPCs provide a cellular link between leptin and immune regulation of body weight, unifying #neuroendocrinology and #immunometabolism as previously disconnected fields of #obesity research. Read on: https://lnkd.in/g8hN2KEF #research #biotech #innovation #immune #bodyweight #metabolic

#IGFBP2 Unlocking the #Obesity Puzzle: Targeting the Adipogenesis-Hypertrophy Switch! Researchers have uncovered a promising avenue for tackling obesity: targeting the balance between fat cell creation (adipogenesis) and enlargement (hypertrophy). By honing in on this adipogenesis-hypertrophy switch, scientists aim to develop more effective therapies. This breakthrough offers hope for innovative approaches to combat obesity-related health concerns. As scientists continue to unravel the mysteries of fat cell biology, the prospects for more targeted and personalized obesity therapies are brighter than ever. https://lnkd.in/e89cUXfr Search #IGFBP2 on #dimabio.com to find the bioactive protein for this target!

#drugchallenge day3! 👏👏👏 #SGLT2 inhibitors and MoAs How are connected glucose metolism,Sirtuins (#epigenetic enzymes),autophagy and metabolic/heart diseases? SGLT2 Inhibitors, Lower blood glucose by blocking glucose reabsorption in kidneys. Benefits: Improve glycemic control, promote weight loss, reduce blood pressure, and offer cardiovascular and renal protection. What do we know about Sirtuins? Role: NAD+-dependent enzymes, HDACs that influence epigenetic landscape, regulate gene expression, regulate aging, metabolism, and stress responses. Key Players: SIRT1 and SIRT3 enhance insulin sensitivity and mitochondrial function. Autophagy: Process: Degrades and recycles cellular debris, maintaining homeostasis. Benefits: Regulates metabolism, improves insulin sensitivity, and protects against disease such as heart and kidney failure MoA: SGLT2 inhibitors improve metabolism, potentially activating sirtuins. Sirtuins (e.g., SIRT1) enhance autophagy, promoting cellular health. SGLT2 inhibitors may indirectly support autophagy through metabolic improvements. Conclusion: SGLT2 inhibitors enhance metabolic health, can activate sirtuins and autophagy, leading to improved cellular function and protection against metabolic diseases. #heartfailure #metabolicdisease #cardiology #drugdevelopment #drugdiscovery #multiomics #agingresearch #aging #olinkproteomics #thermofisherscientific

More than happy to say that the collaborative effort between Hospital del Mar Research Institute, Fundación Pasqual Maragall, Fatty Acid Research Institute, CIBERobn and the California Walnut Board & Commission is starting to show results. Red blood cell omega-3 fatty acids in relation to brain glucose metabolism in unimpaired cognitive individuals at increased risk of Alzheimer's - published in Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. Take a look for free at: ttps://doi.org/10.1002/dad2.12596 In short, red blood cell proportion of alpha-linolenic acid (ALA, the main plant-derived omega-3), which objectively reflects its dietary intake, was associated with more preserved glucose uptake in brain areas vulnerable to hypometabolism in Alzheimer's disease (AD), in particular in individuals with higher apolipoprotein E ε4 allele load. Red blood cell proportion of DHA related to glucose uptake in amyloid beta–positive tau-positive participants, suggesting that DHA might increase brain resistance to AD pathology. Anyway, include sources of omega-3 in your regular diet to keep your brain in shape!

New research from our group at @UCLIoN and @Biodonostia marks a step change in understanding relationship between cholesterol and mitochondria: researchers have discovered that the response to cholesterol scarcity in mitochondria causes problems commonly associated with neurodegenerative diseases. https://lnkd.in/gbchCuEi Specifically, when mitochondria struggle to obtain cholesterol, cells respond by increasing cholesterol to dangerous levels to protect these crucial organelles. The excess cholesterol aggregates in membranes and obstructs the cell’s recycling machinery. This new research shed light on how disruption of the cholesterol-mitochondrial axis contributes to a range of neurological diseases. @MITGEST @Ikerbasque @Biodonostia @4Lilyfoundation @BRUKresearch @TonySchapira; @MikeHanna18 @LondonMito @MRCMitoCluster @ASAP_Research https://lnkd.in/gyQqr9s4