The current understanding of lipid droplets (LDs) in cell biology has evolved from being viewed merely as storage compartments. LDs are now recognized as metabolic hubs that act as cytosolic buffers against the detrimental effects of free fatty acids (FAs). Upon activation, FAs traverse various cellular pathways, including oxidation in mitochondria, integration into complex lipids, or storage in triacylglycerols (TGs). Maintaining a balance among these processes is crucial in cellular FA trafficking, and under metabolically challenging circumstances the routes of FA metabolism adapt to meet the current cellular needs. This typically involves an increased demand for anabolic intermediates or energy and the prevention of redox stress. Surprisingly, LDs accumulate under certain conditions such as amino acid starvation. This review explores the biochemical aspects of FA utilization in both physiological contexts and within cancer cells, focusing on the metabolism of TGs, cholesteryl esters (CEs), and mitochondrial FA oxidation. Emphasis is placed on the potential toxicity associated with non-esterified FAs in cytosolic and mitochondrial compartments. Additionally, we discuss mechanisms that lead to increased LD biogenesis due to an inhibited mitochondrial import of FAs.

• Klíčová slova
• CPT1, ferroptosis, lipid droplets, lipotoxicity, mitochondria, triglycerides,
• MeSH
• lidé MeSH
• lipidová tělíska * metabolismus   MeSH
• mastné kyseliny * metabolismus   MeSH
• metabolismus lipidů MeSH
• mitochondrie * metabolismus   MeSH
• oxidace-redukce MeSH
• triglyceridy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• mastné kyseliny * MeSH
• triglyceridy MeSH

We asked whether acute redox signaling from mitochondria exists concomitantly to fatty acid- (FA-) stimulated insulin secretion (FASIS) at low glucose by pancreatic β-cells. We show that FA β-oxidation produces superoxide/H2O2, providing: i) mitochondria-to-plasma-membrane redox signaling, closing KATP-channels synergically with elevated ATP (substituting NADPH-oxidase-4-mediated H2O2-signaling upon glucose-stimulated insulin secretion); ii) activation of redox-sensitive phospholipase iPLA2γ/PNPLA8, cleaving mitochondrial FAs, enabling metabotropic GPR40 receptors to amplify insulin secretion (IS). At fasting glucose, palmitic acid stimulated IS in wt mice; palmitic, stearic, lauric, oleic, linoleic, and hexanoic acids also in perifused pancreatic islets (PIs), with suppressed 1st phases in iPLA2γ/PNPLA8-knockout mice/PIs. Extracellular/cytosolic H2O2-monitoring indicated knockout-independent redox signals, blocked by mitochondrial antioxidant SkQ1, etomoxir, CPT1 silencing, and catalase overexpression, all inhibiting FASIS, keeping ATP-sensitive K+-channels open, and diminishing cytosolic [Ca2+]-oscillations. FASIS in mice was a postprandially delayed physiological event. Redox signals of FA β-oxidation are thus documented, reaching the plasma membrane, essentially co-stimulating IS.

• Klíčová slova
• Fatty acid-stimulated insulin secretion, GPR40, Mitochondrial fatty acids, Pancreatic β-cells, Redox signaling, Redox-activated phospholipase iPLA2γ,
• MeSH
• beta-buňky * metabolismus   MeSH
• buněčná membrána * metabolismus   MeSH
• fosfolipasy A2, skupina VI metabolismus   genetika   MeSH
• glukosa metabolismus   MeSH
• inzulin metabolismus   MeSH
• mastné kyseliny * metabolismus   MeSH
• mitochondrie * metabolismus   MeSH
• myši knockoutované MeSH
• myši MeSH
• oxidace-redukce * MeSH
• peroxid vodíku metabolismus   MeSH
• receptory spřažené s G-proteiny MeSH
• sekrece inzulinu * MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Ffar1 protein, mouse MeSH Prohlížeč
• fosfolipasy A2, skupina VI MeSH
• glukosa MeSH
• inzulin MeSH
• mastné kyseliny * MeSH
• peroxid vodíku MeSH
• Pla2g6 protein, mouse MeSH Prohlížeč
• receptory spřažené s G-proteiny MeSH