Induction of Autophagy by Palmitic Acid via Protein Kinase C-mediated Signaling Pathway Independent of mTOR (Mammalian Target of Rapamycin)

Abstract

Background: Palmitic acid is a saturated fatty acid known to cause lipotoxicity in cells. Results: Palmitic acid induces autophagy, which is independent of mTOR regulation. Conclusion: Palmitic acid-mediated autophagy is regulated via PKC-␣ and acts as a cell survival mechanism. Significance: Our data reveal a novel mechanism underlying free fatty acid-mediated autophagy and suggest the importance of autophagy in bioactivity of fatty acids.

Lipin-1 Regulates Autophagy Clearance and Intersects with Statin Drug Effects in Skeletal Muscle

“…The role of DAG in this process is likely linked to its function as a lipid second messenger. DAG activates a signaling cascade involving protein kinase C, with subsequent activation of the class III phosphatidylinositol 3-kinase, Vps34, which is involved in autophagosome formation and maturation (Eisenberg-Lerner and Kimchi, 2012; Shibasaki et al, 2009; Tan et al, 2012). We hypothesized that lipin-1–generated DAG is important in autolysosome formation, and that lack of lipin-1 impairs PKC and Vps34 activation.…”

Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders

“…Knock down of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a potent regulator of autophagy, reduced PMA‐induced NETosis in HL‐60 cells and overexpression increased it 76. PKC has been shown to stimulate autophagy which in response to certain stimuli can be independent of mTOR, offering a potential explanation for this discrepancy 77. Figure 2 demonstrates how different stimuli resulting in NETosis can have differential effects on autophagy.…”

Time-dependent cellular response in the liver and heart in a dietary-induced obese mouse model: the potential role of ER stress and autophagy

“…Moreover, a cell model demonstrated a pro-survival role of autophagy in the pathogenesis of NAFLD. Tan et al [25] found that restoring autophagy function prevents hepatocyte apoptosis upon palmitate lipotoxicity. Our study showed that autophagy was initiated after 4 weeks of HFD consumption, but not after 16 weeks of HFD consumption, whereas apoptosis was activated after receiving the HFD for 8 weeks.…”