scholarly journals FABP3-mediated membrane lipid saturation alters fluidity and induces ER stress in skeletal muscle with aging

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Seung-Min Lee ◽  
Seol Hee Lee ◽  
Youngae Jung ◽  
Younglang Lee ◽  
Jong Hyun Yoon ◽  
...  

Abstract Sarcopenia is characterized by decreased skeletal muscle mass and function with age. Aged muscles have altered lipid compositions; however, the role and regulation of lipids are unknown. Here we report that FABP3 is upregulated in aged skeletal muscles, disrupting homeostasis via lipid remodeling. Lipidomic analyses reveal that FABP3 overexpression in young muscles alters the membrane lipid composition to that of aged muscle by decreasing polyunsaturated phospholipid acyl chains, while increasing sphingomyelin and lysophosphatidylcholine. FABP3-dependent membrane lipid remodeling causes ER stress via the PERK-eIF2α pathway and inhibits protein synthesis, limiting muscle recovery after immobilization. FABP3 knockdown induces a young-like lipid composition in aged muscles, reduces ER stress, and improves protein synthesis and muscle recovery. Further, FABP3 reduces membrane fluidity and knockdown increases fluidity in vitro, potentially causing ER stress. Therefore, FABP3 drives membrane lipid composition-mediated ER stress to regulate muscle homeostasis during aging and is a valuable target for sarcopenia.

1990 ◽  
Vol 10 (3) ◽  
pp. 263-270 ◽  
Author(s):  
J. Pascal Zimmer ◽  
Hans A. Lehr ◽  
Christoph Hübner ◽  
Stephan G. Lindner ◽  
Ralf Ramsperger ◽  
...  

Although most non-human primates, except the chimpanzee and the gibbon in vivo are not infectible by HIV-1, lymphocytes of several of these species can be infected by HIV-1 in vitro.In order to investigate whether the in vitro infectibility of primate lymphocytes might be attributed to plasma membrane adaptation processes or to serum factors, we compared HIV-1 infectibility of cultivated peripheral blood lymphocytes of macaques and of baboons on day one and on day ten of cultivation. These data were correlated to plasma membrane lipid composition and membrane fluidity.We found a correlation between increased HIV-1 in vitro infectibility and changes in plasma membrane lipid composition resulting in decreased membrane fluidity of cultured primate lymphocytes.


2018 ◽  
Vol 20 (43) ◽  
pp. 27294-27304 ◽  
Author(s):  
Rodrigo Aguayo-Ortiz ◽  
John E. Straub ◽  
Laura Dominguez

Insight into the effect of bilayer lipid composition on the GS structural ensemble and function using multiscale computational modeling approaches.


FEBS Letters ◽  
2018 ◽  
Vol 593 (1) ◽  
pp. 88-96 ◽  
Author(s):  
Maria V. Selvadurai ◽  
Rose J. Brazilek ◽  
Mitchell J. Moon ◽  
Jean‐Yves Rinckel ◽  
Anita Eckly ◽  
...  

Membranes ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 919
Author(s):  
Manuel Torres ◽  
Sebastià Parets ◽  
Javier Fernández-Díaz ◽  
Roberto Beteta-Göbel ◽  
Raquel Rodríguez-Lorca ◽  
...  

Membranes are mainly composed of a lipid bilayer and proteins, constituting a checkpoint for the entry and passage of signals and other molecules. Their composition can be modulated by diet, pathophysiological processes, and nutritional/pharmaceutical interventions. In addition to their use as an energy source, lipids have important structural and functional roles, e.g., fatty acyl moieties in phospholipids have distinct impacts on human health depending on their saturation, carbon length, and isometry. These and other membrane lipids have quite specific effects on the lipid bilayer structure, which regulates the interaction with signaling proteins. Alterations to lipids have been associated with important diseases, and, consequently, normalization of these alterations or regulatory interventions that control membrane lipid composition have therapeutic potential. This approach, termed membrane lipid therapy or membrane lipid replacement, has emerged as a novel technology platform for nutraceutical interventions and drug discovery. Several clinical trials and therapeutic products have validated this technology based on the understanding of membrane structure and function. The present review analyzes the molecular basis of this innovative approach, describing how membrane lipid composition and structure affects protein-lipid interactions, cell signaling, disease, and therapy (e.g., fatigue and cardiovascular, neurodegenerative, tumor, infectious diseases).


Aging ◽  
2016 ◽  
Vol 8 (1) ◽  
pp. 127-146 ◽  
Author(s):  
Leslie M. Baehr ◽  
Daniel W.D. West ◽  
George Marcotte ◽  
Andrea G. Marshall ◽  
Luis Gustavo De Sousa ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Nathalie Rion ◽  
Perrine Castets ◽  
Shuo Lin ◽  
Leonie Enderle ◽  
Judith R. Reinhard ◽  
...  

Abstract Background The mammalian target of rapamycin complex 2 (mTORC2), containing the essential protein rictor, regulates cellular metabolism and cytoskeletal organization by phosphorylating protein kinases, such as PKB/Akt, PKC, and SGK. Inactivation of mTORC2 signaling in adult skeletal muscle affects its metabolism, but not muscle morphology and function. However, the role of mTORC2 in adult muscle stem cells (MuSCs) has not been investigated. Method Using histological, biochemical, and molecular biological methods, we characterized the muscle phenotype of mice depleted for rictor in the Myf5-lineage (RImyfKO) and of mice depleted for rictor in skeletal muscle fibers (RImKO). The proliferative and myogenic potential of MuSCs was analyzed upon cardiotoxin-induced injury in vivo and in isolated myofibers in vitro. Results Skeletal muscle of young and 14-month-old RImyfKO mice appeared normal in composition and function. MuSCs from young RImyfKO mice exhibited a similar capacity to proliferate, differentiate, and fuse as controls. In contrast, the number of MuSCs was lower in young RImyfKO mice than in controls after two consecutive rounds of cardiotoxin-induced muscle regeneration. Similarly, the number of MuSCs in RImyfKO mice decreased with age, which correlated with a decline in the regenerative capacity of mutant muscle. Interestingly, reduction in the number of MuSCs was also observed in 14-month-old RImKO muscle. Conclusions Our study shows that mTORC2 signaling is dispensable for myofiber formation, but contributes to the homeostasis of MuSCs. Loss of mTORC2 does not affect their myogenic function, but impairs the replenishment of MuSCs after repeated injuries and their maintenance during aging. These results point to an important role of mTORC2 signaling in MuSC for muscle homeostasis.


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