Bêta-oxydation | EPFL Graph Search

La β-oxydation, communément appelée spirale de Lynen, est la principale voie métabolique de dégradation des molécules d'acides gras pour produire : *d'une part de l', dont le groupe acétyle est oxydé par le cycle de Krebs *et d'autre part du NADH et du , dont les électrons à haut potentiel alimentent la chaîne respiratoire. Dans les cellules eucaryotes, la β-oxydation se déroule en aérobiose dans la matrice mitochondriale, mais aussi dans d'autres organites que sont les peroxysomes et, chez les plantes, les glyoxysomes. Dans les cellules procaryotes, elle se déroule dans le cytosol. Activation des acides gras et transport par la navette de la carnitine redresse=2|vignette| Transfert des groupes acyle de l'acyl-CoA du cytosol vers la matrice mitochondriale sous forme d'acylcarnitine via la carnitine-acylcarnitine translocase. Les acides gras sont dégradés dans les mitochondries sous forme d'acyl-CoA. Ces derniers se forment sous l'action d'une synthétase, qui catalyse

Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism

Ludger Jan Elzuë Goeminne, Vera Monica Lemos Da Silva, Barbara Moreira Crisol, Eduardo Rochete Ropelle

Hypothalamic interleukin-6 (IL6) exerts a broad metabolic control. Here, we demonstrated that IL6 activates the ERK1/2 pathway in the ventromedial hypothalamus (VMH), stimulating AMPK/ACC signaling and fatty acid oxidation in mouse skeletal muscle. Bioinformatics analysis revealed that the hypothalamic IL6/ERK1/2 axis is closely associated with fatty acid oxidation– and mitochondrial-related genes in the skeletal muscle of isogenic BXD mouse strains and humans. We showed that the hypothalamic IL6/ERK1/2 pathway requires the α2-adrenergic pathway to modify fatty acid skeletal muscle metabolism. To address the physiological relevance of these findings, we demonstrated that this neuromuscular circuit is required to underpin AMPK/ACC signaling activation and fatty acid oxidation after exercise. Last, the selective down-regulation of IL6 receptor in VMH abolished the effects of exercise to sustain AMPK and ACC phosphorylation and fatty acid oxidation in the muscle after exercise. Together, these data demonstrated that the IL6/ERK axis in VMH controls fatty acid metabolism in the skeletal muscle.

2022

CDK4 Phosphorylates AMPK alpha 2 to Inhibit Its Activity and Repress Fatty Acid Oxidation

Caterina Collodet, Anita Nasrallah

The roles of CDK4 in the cell cycle have been extensively studied, but less is known about the mechanisms underlying the metabolic regulation by CDK4. Here, we report that CDK4 promotes anaerobic glycolysis and represses fatty acid oxidation in mouse embryonic fibroblasts (MEFs) by targeting the AMP- activated protein kinase (AMPK). We also show that fatty acid oxidation (FAO) is specifically induced by AMPK complexes containing the alpha 2 subunit. Moreover, we report that CDK4 represses FAO through direct phosphorylation and inhibition of AMPK alpha 2. The expression of non- phosphorylatable AMPK alpha 2 mutants, or the use of a CDK4 inhibitor, increased FAO rates in MEFs and myotubes. In addition, Cdk4(-/-) mice have increased oxidative metabolism and exercise capacity. Inhibition of CDK4 mimicked these alterations in normal mice, but not when skeletal muscle was AMPK deficient. This novel mechanism explains how CDK4 promotes anabolism by blocking catabolic processes (FAO) that are activated by AMPK.

Cell Press2017

Controlling topology, dynamics and function of polymer brushes via post-polymerization modification

Piotr Mocny

Polymer brushes are a class of thin coatings, where each of chains is tethered to the underlying substrate via one chain end. Densely grafted polymer brushes feature a stretched chain conformation, which in a unique way enhances their lubrication and non-biofouling properties. Polymer brushes also present a high density of functional groups, whose exposure in solvated brushes is useful for catalysis or in medical applications, including diagnostics. Advances in surface-initiated controlled radical polymerizations (SI-CRP) have facilitated the synthesis of high grafting density polymer brushes with a great control over film thickness / polymer molecular weight and composition. These techniques enable access to plethora of polymer architectures. Due to the fact that SI-CRP strategies allow the use of a wide range of monomers, multiple routes for the post-polymerization modification of polymer brushes are possible. Combination of SI-CRP with post-polymerization modification provides possibilities to systematically study architecture- and composition-property relationships of polymer brushes. This Thesis aims to manipulate the topology and crosslinking dynamics of polymer brushes, whose effect on properties of the coatings will help to understand these relationships. Additionally, functions of polymer brushes can be extended by their modification. As an example, incorporation of nanoparticles is a way to provide catalytic functions. Swelling of the nanoparticle â polymer brush assemblies can expose the catalytically active sites and potentially maximize its activities. Chapter 1 provides an overview of manipulation strategies over the composition and topologies of polymer brushes, routes toward their crosslinking and methods for assembly of nanoparticles within polymer brush matrices. Chapter 2 demonstrates a two-step post-polymerization synthetic approach to generate loop polymer brushes with potentially improved non-biofouling and lubrication properties. In the first step, olefin groups are installed at the polymer chain-ends and then metathesis is used to induce loop closure. Chapter 3 presents a synthetic strategy to install different crosslinks onto polymer brush platforms. It comprises a two step-process: surface-initiated atom transfer polymerization (SI-ATRP) to generate a copolymer platform bearing azide groups, and copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) using propargyl-modified thiol precursors. Multiple crosslinking and decrosslinking cycles are studied under oxidative and reductive conditions. Chapter 4 explores the catalytic properties of 3-dimensional (3D) assemblies of amorphous molybdenum sulfide in polymer brushes as a template. Poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes are grown from highly-oriented pyrolytic graphite (HOPG) and used to bind anionic tetrathiomolybdate through an anion exchange reaction. In a final oxidation step, the polymer-bound tetrathiomolybdate is converted into the amorphous MoSx catalyst. The performance of polymer brush-catalyst system during hydrogen evolution reaction (HER) is studied.

EPFL2019

Controlling topology, dynamics and function of polymer brushes via post-polymerization modification

Piotr Mocny

EPFL2019