Biochimica et biophysica acta. Molecular and cell biology of lipids最新文献

Fatty acids play an important role in regulating gluconeogenesis through the metabolite acetyl-CoA, however, the underlying mechanisms on how fatty acid oxidation provides acetyl-CoA for the stimulation of pyruvate carboxylase and gluconeogenesis are not fully demonstrated. As a fatty acid β-oxidation system exists in peroxisomes and the acetyl-CoA derived from peroxisomal β-oxidation can be transported into mitochondria through the intermediate acetyl-carnitine, we hypothesize that this β-oxidation system might play a role in regulating pyruvate carboxylase and gluconeogenesis. The study demonstrates a mechanism by which fatty acids activate pyruvate carboxylase through the acetyl-CoA derived from peroxisomal β-oxidation. Induction of peroxisomal fatty acid β-oxidation results in excessive generation of acetyl-carnitine, which significantly elevates liver acetyl-CoA level and stimulates pyruvate carboxylase and gluconeogenesis in fasting mice. Specific inhibition of peroxisomal β-oxidation suppresses glucose production and lowers fasting glucose by reducing acetyl-CoA generation in the liver of diabetic mice. It is proposed that induction of peroxisomal β-oxidation serves as a pathogenic mechanism for fatty acids induced hyperactivation of pyruvate carboxylase and gluconeogenesis and targeting peroxisomal β-oxidation might be a potential pathway in treating diabetes through reducing acetyl-CoA generation and suppressing gluconeogenesis.

Syntaxin 11(STX11), a SNARE family protein, regulates vesicular trafficking and cytokinesis, yet its functional role in colorectal cancer (CRC) pathogenesis remains poorly understood. Here, we identify STX11 as a critical regulator that potentiates CRC progression in vivo and in vitro. Mechanistically, STX11 modulates the AMPK signaling pathway in a palmitoylation-dependent manner, attenuating ACC phosphorylation to enhance its enzymatic activity and stimulate de novo lipogenesis. Genetic ablation of STX11 significantly impedes tumorigenesis in an AOM/DSS-induced CRC mouse model. Our findings establish STX11 as a critical regulator of lipid metabolism in CRC progression and nominate it as a promising therapeutic target.

Previous studies have revealed the expression of anti-complement factors on the surface of sperm across various species to resist attacks from complement components in reproductive tracts. Here we show that the anti-complement factor The caput of the porcine epididymis specifically expresses C4BPA, which is then transported to the surface of sperm via epididymosomes. The presence of C4BPA in epididymosomes depends on its palmitoylation modification, specifically at the Cys13 and Cys23 residues. ZDHHC8 has been pinpointed as the palmitoyl transferase that carries out this modification. Palmitoylated C4BPA in epididymosomes significantly resists attacks by complement C4 on sperm, maintaining porcine sperm motility. Our findings reveal a critical role for palmitoylated C4BPA in mitigating C4-mediated damage to sperm, highlighting its physiological relevance in preserving sperm motility and viability.

Myogenic differentiation plays a vital role in embryonic muscle formation, postnatal muscle regeneration and repair processes. Exogenous fatty acids (FAs) influence physiological functions of skeletal muscle. Nevertheless, our grasp of how various types of FAs influence skeletal muscle differentiation remains limited and inconsistent. In this study, we comprehensively evaluated the effects of the six prevalent FAs on metabolism, proliferation, and differentiation of skeletal muscle precursor cells. We employed C2C12 myoblasts and treated them with three saturated FAs: palmitic acid (PA), stearic acid (SA), myristic acid (MA), as well as three unsaturated FAs: docosahexaenoic acid (DHA), oleic acid (OA), linoleic acid (LA). We found OA and LA facilitated proliferation of C2C12 cells through MAPK-ERK1/2 pathway, whereas DHA and MA had a mild inhibitory effect on this process. No significant effect on cell proliferation was noted with PA or SA treatment. Interestingly, both PA and MA unexpectedly enhanced myogenic differentiation, evidenced by promoting cell cycle exit through increased p21 levels, alongside myotube formation via upregulation of myogenin and MyHC by PI3K/Akt signaling pathway. In contrast, SA and all three unsaturated FAs considerably hindered myogenic differentiation. Collectively, these findings suggest PA and MA might serve as beneficial FAs to support skeletal muscle differentiation. Furthermore, even within the same categories of FAs, such as saturated and unsaturated, their effects on myogenesis differ and may even be contradictory. This observation challenges the traditional perceptions regarding FAs and provides a novel perspective for understanding the impact of different FAs on myogenesis.

Phosphoinositides, most prominently phosphatidylinositol (4,5)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate, regulate the activities of a wide range of proteins that control the polymerization, depolymerization, and branching of actin filaments. This phosphoinositide-mediated remodeling of the actin cytoskeleton is crucial for a many cellular functions, including migration, division, and intracellular organelle transport. As a unifying theme in this review, we have chosen to focus on the role of phosphoinositides in regulating actin dynamics during dendritic spine plasticity. As in other biological systems, actin polymerization and branching drive morphological changes in dendritic spines by exerting force on the plasma membrane, creating structures such as filopodial protrusions and bulbous spine heads. Activity-dependent changes in the number, size, and shape of dendritic spines underlie fundamental brain functions such as learning and memory and are often disrupted in cognitive and neurological disorders. Hence, the control of actin regulatory proteins in dendritic spines by phosphoinositides has been, and remains, an extremely active area of investigation.

The increasing global demand for aquaculture products requires sustainable fish feed strategies. This study investigated how replacing fish oil with microbial oil (MO) and canola oil (CO) combinations affects lipid metabolism and gene expression in Atlantic salmon (Salmo salar), correlating these changes with phospholipid profiles. Four isonitrogenous, isoenergetic diets were tested: 20% fish oil (FO); 10% fish oil +10% CO (FO/CO); 15% CO + 5% MO (CO/MO); and 10% CO + 10% MO (MO-10). After 16 weeks, liver and skeletal muscle tissues were sampled for lipidomics and gene expression analysis. Multivariate analysis revealed distinct dietary group separations. The CO/MO diet induced the highest hepatic expression of de novo lipogenesis gene fatty acid synthase b while suppressing fatty acid oxidation marker acyl-CoA oxidase 1, indicating lipid storage promotion. Inflammatory marker arachidonate 12-lipoxygenase was associated with groups with reduced ω3 LC-PUFA (FO/CO, CO/MO). Muscle tissue showed subtler but diet-specific gene expression patterns, with de novo lipogenesis genes (stearoyl-CoA desaturase b, ATP citrate lyase 2) associated with decreased ω3 LC-PUFA (i.e., EPA and DHA) and correlating with monounsaturated fatty acids. The MO-10 group mirrored FO-fed fish, demonstrating successful fish oil replacement at 10% inclusion. Lipidomic pathway analysis revealed diet-induced phospholipid remodelling, for example, enhanced PE-to-PC conversion in the FO/CO and CO/MO groups, suggesting membrane-fluidity and inflammatory modulation. These results demonstrate tissue-specific metabolic adaptations to alternative lipid sources, with 10% CO + 10% MO effectively substituting for fish oil while maintaining metabolic profiles in the trial timeline. The findings advance our understanding of lipid metabolism regulation in salmon and support sustainable feed development for aquaculture and enhanced nutritional quality of aquaculture products.