Insulin activates intracellular transport of lipid droplets to release triglycerides from the liver
| Autor: | Mukesh Kumar, Siddhesh S. Kamat, Srikant Ojha, Priyanka Rai, Roop Mallik, Alaumy Joshi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
Liver cytology medicine.medical_treatment Article Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Internal medicine Lipid droplet Hyperlipidemia medicine Animals Insulin Research Articles Cells Cultured Triglycerides 030304 developmental biology 0303 health sciences biology Triglyceride 030302 biochemistry & molecular biology Biological Transport Lipid Droplets Cell Biology Phosphatidic acid medicine.disease Rats 3. Good health Insulin receptor Endocrinology Liver chemistry biology.protein Lipoprotein |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | Kumar et al. describe a detailed pathway for channeling fat from the liver into blood across fed/fasted cycles. Insulin, phosphatidic acid, and kinesin collaborate in hepatocytes to deliver lipid droplets to the smooth ER, where they are catabolized to supply fat for lipoprotein production and secretion. Triglyceride-rich lipid droplets (LDs) are catabolized with high efficiency in hepatocytes to supply fatty acids for producing lipoprotein particles. Fasting causes a massive influx of adipose-derived fatty acids into the liver. The liver in the fasted state is therefore bloated with LDs but, remarkably, still continues to secrete triglycerides at a constant rate. Here we show that insulin signaling elevates phosphatidic acid (PA) dramatically on LDs in the fed state. PA then signals to recruit kinesin-1 motors, which transport LDs to the peripherally located smooth ER inside hepatocytes, where LDs are catabolized to produce lipoproteins. This pathway is down-regulated homeostatically when fasting causes insulin levels to drop, thus preventing dangerous elevation of triglycerides in the blood. Further, we show that a specific peptide against kinesin-1 blocks triglyceride secretion without any apparent deleterious effects on cells. Our work therefore reveals fundamental mechanisms that maintain lipid homeostasis across metabolic states and leverages this knowledge to propose a molecular target against hyperlipidemia. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|