Triglyceride Forum

201 posts

Triglyceride Forum

Triglyceride Forum

@TriglycerideF

Katılım Aralık 2020
77 Takip Edilen283 Takipçiler
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Pablo Corral MD
Pablo Corral MD@drpablocorral·
👉 ANGPTL3: Beyond plasma lipid regulation — an intrahepatic story 👆 Key mechanistic insights from recent experimental data: 1️⃣ ANGPTL3 deficiency reduces ApoB100 secretion (~50%) → Fewer TG-rich lipoproteins are assembled and released by hepatocytes. 2️⃣ Mechanism: increased intracellular ApoB degradation → Particles are destroyed before secretion, not just cleared in plasma. 3️⃣ LDLR status matters: – With functional LDLR → early (pre-secretory) degradation – Without LDLR → late/post-Golgi degradation pathways 4️⃣ No hepatic lipid accumulation despite impaired lipoprotein export → Contrary to what happens with MTP or ApoB inhibition. 5️⃣ Why no steatosis? Adaptive metabolic shift: – ↓ TG secretion – ↑ Fatty acid oxidation – ↓ Lipogenesis gene programs (PPAR-α driven) 6️⃣ LDL lowering persists even without LDLR → Supports LDLR-independent clearance pathways → Mechanistic basis for efficacy in HoFH. 👆 Take-home message ANGPTL3 inhibition doesn’t just enhance lipolysis in plasma — it reprograms hepatic lipoprotein production and lipid metabolism at the source. 📍 A dual mechanism: ↓ Production + ↑ Clearance. 🔗 Open Access jlr.org/article/S0022-… @society_eas @TriglycerideF
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