scholarly journals Regulation of Triglyceride Metabolism II. Function of mitochondrial GPAT1 in the regulation of triacylglycerol biosynthesis and insulin action

2007 ◽  
Vol 292 (5) ◽  
pp. G1195-G1199 ◽  
Author(s):  
Maria R. Gonzalez-Baró ◽  
Tal M. Lewin ◽  
Rosalind A. Coleman
Keyword(s):  
Intracellular Signaling ◽  
Insulin Action ◽  
The Other ◽  
Mitochondrial Outer Membrane ◽  
Reciprocal Regulation ◽  
Intracellular Signaling Pathways ◽  
Peripheral Insulin Resistance ◽  
Triacylglycerol Synthesis ◽  
Amp Activated Protein Kinase ◽  
Carnitine Palmitoyltransferase 1

GPAT1, one of four known glycerol-3-phosphate acyltransferase isoforms, is located on the mitochondrial outer membrane, allowing reciprocal regulation with carnitine palmitoyltransferase-1. GPAT1 is upregulated transcriptionally by insulin and SREBP-1c and downregulated acutely by AMP-activated protein kinase, consistent with a role in triacylglycerol synthesis. Knockout and overexpression studies suggest that GPAT1 is critical for the development of hepatic steatosis and that steatosis initiated by overexpression of GPAT1 causes hepatic, and perhaps also peripheral, insulin resistance. Future questions include the function of GPAT1 in relation to the other GPAT isoforms and whether the lipid intermediates synthesized by GPAT and downstream enzymes in the pathway of glycerolipid biosynthesis participate in intracellular signaling pathways.

scholarly journals AMPK Function in Mammalian Spermatozoa

2018 ◽  
Vol 19 (11) ◽  
pp. 3293 ◽  
Author(s):  
David Martin-Hidalgo ◽  
Ana Hurtado de Llera ◽  
Violeta Calle-Guisado ◽  
Lauro Gonzalez-Fernandez ◽  
Luis Garcia-Marin ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Cell Metabolism ◽  
Extracellular Medium ◽  
Assisted Reproduction Techniques ◽  
Cellular Energy ◽  
Intracellular Signaling Pathways ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase ◽  
Mammalian Spermatozoa

AMP-activated protein kinase AMPK regulates cellular energy by controlling metabolism through the inhibition of anabolic pathways and the simultaneous stimulation of catabolic pathways. Given its central regulator role in cell metabolism, AMPK activity and its regulation have been the focus of relevant investigations, although only a few studies have focused on the AMPK function in the control of spermatozoa’s ability to fertilize. This review summarizes the known cellular roles of AMPK that have been identified in mammalian spermatozoa. The involvement of AMPK activity is described in terms of the main physiological functions of mature spermatozoa, particularly in the regulation of suitable sperm motility adapted to the fluctuating extracellular medium, maintenance of the integrity of sperm membranes, and the mitochondrial membrane potential. In addition, the intracellular signaling pathways leading to AMPK activation in mammalian spermatozoa are reviewed. We also discuss the role of AMPK in assisted reproduction techniques, particularly during semen cryopreservation and preservation (at 17 °C). Finally, we reinforce the idea of AMPK as a key signaling kinase in spermatozoa that acts as an essential linker/bridge between metabolism energy and sperm’s ability to fertilize.

scholarly journals Molecular dynamics modeling of the interaction of cationic fluorescent lipid peroxidation-sensitive probes with the mitochondrial membrane

2019 ◽  
Vol 486 (4) ◽  
pp. 509-513
Author(s):  
A. M. Nesterenko ◽  
E. G. Kholina ◽  
K. G. Lyamzaev ◽  
A. Y. Mulkidzhanyan ◽  
B. V. Chernyak
Keyword(s):  
Lipid Peroxidation ◽  
Intracellular Signaling ◽  
Mitochondrial Membrane ◽  
Aging Process ◽  
Unsaturated Fatty Acids ◽  
The Other ◽  
Dynamics Modeling ◽  
Intracellular Signaling Pathways ◽  
Mitochondrial Inner Membrane ◽  
Molecular Dynamics Modeling

Cardiolipin (CL) plays a central role in lipid peroxidation (LPO) of the mitochondrial inner membrane due to higher content of unsaturated fatty acids in CL in comparison with the other phospholipids. CL oxidation plays an important role in the regulation of various intracellular signaling pathways and its excessive oxidation contributes to the development of various pathologies and, possibly, participates in the aging process. Mitochondria-targeted antioxidants containing triphenylphosphonium cation (TPP+) effectively protect CL from oxidation. It is assumed that fluorescent probes on the basis of the C11-BODIPY fluorophore sensitive to LPO and containing TPP+ can selectively register CL oxidation. To test this possibility, we carried out a molecular dynamic simulation of such probes in a model mitochondrial membrane. It is shown that the probes are located in the membrane at the same depth as the unsaturated bonds in CL molecules sensitive to oxidation. Increasing the length of the linker that binds the fluorophore and TPP+ residue has little effect on the position of the probe in the membrane. This indicates the possibility of modifying the linker to increase the selectivity of the probes to CL.

scholarly journals AMPK Activity: A Primary Target for Diabetes Prevention with Therapeutic Phytochemicals

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4050
Author(s):  
Min-Yu Chung ◽  
Hyo-Kyoung Choi ◽  
Jin-Taek Hwang
Keyword(s):  
Metabolic Syndrome ◽  
Intracellular Signaling ◽  
Blood Glucose Control ◽  
Mechanisms Of Action ◽  
Primary Target ◽  
Intracellular Signaling Pathways ◽  
Ancient Times ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

Diabetes is a metabolic syndrome characterized by inadequate blood glucose control and is associated with reduced quality of life and various complications, significantly shortening life expectancy. Natural phytochemicals found in plants have been traditionally used as medicines for the prevention of chronic diseases including diabetes in East Asia since ancient times. Many of these phytochemicals have been characterized as having few side effects, and scientific research into the mechanisms of action responsible has accumulated mounting evidence for their efficacy. These compounds, which may help to prevent metabolic syndrome disorders including diabetes, act through relevant intracellular signaling pathways. In this review, we examine the anti-diabetic efficacy of several compounds and extracts derived from medicinal plants, with a focus on AMP-activated protein kinase (AMPK) activity.

scholarly journals Multiple intracellular signaling pathways orchestrate adipocytic differentiation of human bone marrow stromal stem cells

2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Dalia Ali ◽  
Sarah Abuelreich ◽  
Nora Alkeraishan ◽  
Najla Bin Shwish ◽  
Rimi Hamam ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Signaling Pathways ◽  
Pathway Analysis ◽  
Intracellular Signaling ◽  
Adipocyte Differentiation ◽  
Human Bone ◽  
The Other ◽  
Human Bone Marrow ◽  
Intracellular Signaling Pathways

Bone marrow adipocyte formation plays a role in bone homeostasis and whole body energy metabolism. However, the transcriptional landscape and signaling pathways associated with adipocyte lineage commitment and maturation are not fully delineated. Thus, we performed global gene expression profiling during adipocyte differentiation of human bone marrow stromal (mesenchymal) stem cells (hMSCs) and identified 2,589 up-regulated and 2,583 down-regulated mRNA transcripts. Pathway analysis on the up-regulated gene list untraveled enrichment in multiple signaling pathways including insulin receptor signaling, focal Adhesion, metapathway biotransformation, a number of metabolic pathways e.g. selenium metabolism, Benzo(a)pyrene metabolism, fatty acid, triacylglycerol, ketone body metabolism, tryptophan metabolism, and catalytic cycle of mammalian flavin-containing monooxygenase (FMOs). On the other hand, pathway analysis on the down-regulated genes revealed significant enrichment in pathways related to cell cycle regulation. Based on these data, we assessed the effect of pharmacological inhibition of FAK signaling using PF-573228, PF-562271, and InsR/IGF-1R using NVP-AEW541 and GSK-1904529A on adipocyte differentiation. hMSCs exposed to FAK or IGF-1R/InsR inhibitors exhibited fewer adipocyte formation (27–58% inhibition, P<0005). Concordantly, the expression of adipocyte-specific genes AP2, AdipoQ, and CEBPα was significantly reduced. On the other hand, we did not detect significant effects on cell viability as a result of FAK or IGF-1R/InsR inhibition. Our data identified FAK and insulin signaling as important intracellular signaling pathways relevant to bone marrow adipogenesis.

scholarly journals Interaction of dual intracellular signaling pathways activated by the melanocortin-3 receptor.

1994 ◽  
Vol 269 (18) ◽  
pp. 13162-13166
Author(s):  
Y. Konda ◽  
I. Gantz ◽  
J. DelValle ◽  
Y. Shimoto ◽  
H. Miwa ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Intracellular Signaling Pathways
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