Sharp Laboratory

Obesity phenotypes and cardiovascular disease ahajrnls.org/4ruMCVl

Hyperinsulinemia, adiposity, causality and #obesity The latest perspectives nature.com/articles/s4157…

👉 Metabolic Disorders and Cardiovascular Disease: Key Insights 👆 A recent ESC scientific statement highlights the central role of metabolic dysfunction in cardiovascular disease and the therapeutic implications of emerging cardiometabolic therapies. 👆 Key points: 📍 Cardiovascular disease is increasingly driven by metabolic dysfunction—obesity, type 2 diabetes, and dyslipidaemia act synergistically to accelerate atherosclerosis, heart failure, and arrhythmias. 📍 Metabolic disease disrupts myocardial energetics, promoting metabolic inflexibility, mitochondrial dysfunction, oxidative stress, and lipotoxicity. 📍 Modern cardiometabolic drugs provide benefits beyond glucose lowering. SGLT2 inhibitors and GLP-1–based therapies improve cardiovascular outcomes through pleiotropic mechanisms. 📍 Atherogenic risk extends beyond LDL-C, with triglyceride-rich lipoproteins and Lp(a) contributing to residual cardiovascular risk. 📍 Future progress will require a systems-biology approach, integrating multi-organ mechanisms, multi-omics data, and translational research. 👆 Bottom line: Cardiovascular disease should increasingly be understood as a systemic cardiometabolic disorder rather than an isolated vascular pathology. 🔗 Open Access academic.oup.com/eurheartj/adva… @society_eas @escardio

New ACC/AHA Guidelines published today for lipids address measuring Lp(a) and ApoB jacc.org/doi/10.1016/j.…

Reduced-frequency GLP-1 as a maintenance strategy: in this case series, patients who tapered from weekly semaglutide/tirzepatide to less frequent dosing maintained weight loss, body composition, and metabolic syndrome gains, supporting structured de-escalation to lower burden without sacrificing efficacy. onlinelibrary.wiley.com/doi/full/10.10…

The BELIEVE study, the efficacy and safety of intravenous bimagrumab and open-label subcutaneous semaglutide, alone or in combination, in adults with #obesity nature.com/articles/s4159…

A metabolic atlas of mouse aging: Cell Metabolism cell.com/cell-metabolis…

GLP-1 drugs have intrinsic potent anti-inflammatory action beyond their metabolic beneficial impact on glucose regulation and weight loss @DanielJDrucker @jclinicalinvest jci.org/articles/view/…

3 types of hunger explained "simply" Hunger isn’t just about an empty stomach. Your brain receives signals from body composition, hormones, emotions, and even gut microbes. Here’s how the three major types work: 1️⃣ Homeostatic Hunger (Energy Balance Hunger) This is your body’s “fuel gauge.” It rises and falls based on energy needs and metabolic signals. What drives it: Ghrelin from the stomach stimulates hunger; leptin from fat cells and incretin hormones (GLP-1, PYY, CCK) reduce it. What it does: Ensures your intake matches your energy needs for exercise, growth, and tissue repair. 🟢 Example: After a long run, homeostatic hunger pushes you to replace calories and glycogen. 2️⃣ Hedonic Hunger (Reward-Driven Hunger) This is your “food pleasure” system. It’s triggered by sight, smell, habits, and emotions, not by actual energy needs. What drives it: Brain reward circuits activated by highly palatable foods (sugar, fat, salt). What it does: Encourages eating even when you’re not truly hungry. Weak satiety signals make it harder to stop. 🟢 Example: Craving dessert after dinner even though you’re full. 3️⃣ Microbiota-Driven Hunger (Gut Microbe Hunger) Your gut bacteria also shape hunger signals by producing metabolites that influence hormones and the brain. What drives it: Microbes generate compounds that mimic hunger or satiety signals, affect insulin, and modulate ghrelin, GLP-1, and PYY. What it does: Links gut health to appetite regulation and metabolic control. 🟢 Example: Certain bacterial imbalances may increase cravings or weaken satiety, nudging overeating.

Impact of Semaglutide on fat mass, lean mass and muscle function in patients with obesity: The SEMALEAN study - Alissou - Diabetes, Obesity and Metabolism - Wiley Online Library dom-pubs.onlinelibrary.wiley.com/doi/10.1111/do…

Excellent review article by @DanielJDrucker: GLP-1 medicines beyond diabetes and obesity with benefits for heart, kidney, liver, sleep apnea, substance use disorders, and even neurodegenerative diseases. Next-gen molecules and combo therapies (like #retatrutide and #amycretin) with more weight loss and potentially more benefits. pubmed.ncbi.nlm.nih.gov/40952711/

For obesity in adults and children, a randomized trial of replacing added sugar with sweeteners and sweetness enhancers led to improved weight loss maintenance and a favorable impact on the gut microbiome nature.com/articles/s4225…

BREAKING NEWS The 2025 #NobelPrize in Physiology or Medicine has been awarded to Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi “for their discoveries concerning peripheral immune tolerance.”

In a key Nature #Metabolism paper, 79 experts across 18 countries have put forward consensus standards for #IndirectCalorimetry research to empower scientists to build on each others' results and advance research into #Obesity, #Diabetes, and more. ow.ly/Tkrx50X666t

“I believe this will encourage immunologists and physicians to apply T regulatory cells to treat various immunological diseases.” This year’s Nobel Prize laureate, Shimon Sakaguchi, discovered a new class of T cells that protect the body from autoimmune diseases. Just after the prize announcement we spoke to him about the fundamental research question that kept him dedicated to the field long after many others gave up. Listen to our interview with the happy and surprised laureate: #NobelPrize

New! Online now: The energy resistance principle dlvr.it/TNW23D

Prolonged glucagon exposure and the kidney-helpful or harmful? nature.com/articles/s4146…

Dysregulated Protein s-Nitrosylation Promotes Nitrosative Stress in HFpEF | Circulation Research @LeferLab @VondriskaLab @Sharp_Lab @SmidtHeart @UCLAHealth @USFHealth ahajournals.org/doi/10.1161/CI…

GLP-1 medicines continue to challenge conventional wisdom, with multiple new indications, molecules and mechanisms. Maria Gonzalez Rellan @ChusaGzlzRellan @uoftmedicine provides an update @jama jamanetwork.com/journals/jama/…?

Insightful commentary in @Nature about rapid weight loss with GLP-1 meds which can lead to significant muscle loss or even #sarcopenia. Muscle-preserving strategies, exercise, adequate protein (~1.2-1.6 g/kg/d), creatine, and promising new agents like #bimagrumab and myostatin inhibitors. nature.com/articles/s4157…