Alba Gonzalez-Franquesa

Novo Nordisk Foundation Center for Basic Metabolic Research · Integrative physiology

Skeletal muscle regulates glucose uptake in response to insulin and exercise which is critical for maintaining metabolic health. We conducted a comprehensive phosphoproteomic analysis of skeletal muscle from healthy people in response to an acute bout of exercise or insulin stimulation by a hyperinsulinemic euglycemic clamp. Our analysis revealed 2...

Metabolic plasticity is the ability of a biological system to adapt its metabolic phenotype to different environmental stressors. We used a whole-body and tissue-specific phenotypic, functional, proteomic, metabolomic and transcriptomic approach to systematically assess metabolic plasticity in diet-induced obese mice after a combined nutritional an...

Exercise is an effective strategy in the prevention and treatment of metabolic diseases. Alterations in the skeletal muscle proteome, including post-translational modifications, regulate its metabolic adaptations to exercise. Here, we examined the effect of high-intensity interval training (HIIT) on the proteome and acetylome of human skeletal musc...

The assembly of mitochondrial respiratory complexes into supercomplexes has significant implications for mitochondrial function. This protocol details mitochondrial isolation from mouse tissues and the use of blue native gel electrophoresis (BN-PAGE) to separate pre-identified mitochondrial supercomplexes into different gel bands. We then describe...

Proteomics analysis of skeletal muscle has recently progressed from whole muscle tissue to single myofibers. Here, we further focus on a specific myofiber domain crucial for force transmission from muscle to tendon, the myotendinous junction (MTJ). To overcome the anatomical constraints preventing the isolation of pure MTJs, we performed in-depth a...

Obesity leads to the development of non-alcoholic fatty liver disease (NAFLD) and associated alterations to the plasma proteome. To elucidate the underlying changes associated with obesity, we performed liquid chromatography-tandem mass spectrometry in the liver and plasma of obese leptin-deficient ob/ob mice, and integrated these data with publicl...

Skeletal muscle is an endocrine organ secreting exercise-induced factors (exerkines), which play a pivotal role in inter-organ crosstalk. Using mass spectrometry (MS)-based proteomics, we characterized the secretome and identified thymosin beta-4 (TMSB4X) as the most upregulated secreted protein in the media of contracting C2C12 myotubes. TMSB4X wa...

Skeletal muscle is a major contributor to whole-body glucose homeostasis and is an important endocrine organ. To date, few studies have undertaken the large-scale identification of skeletal muscle-derived secreted proteins (myokines), particularly in response to stimuli that activate pathways governing energy metabolism in health and disease. Where...

Mitochondrial respiratory complex subunits assemble in supercomplexes. Studies of supercomplexes have typically relied upon antibody-based quantification, often limited to a single subunit per respiratory complex. To provide a deeper insight into mitochondrial and supercomplex plasticity, we combine native electrophoresis and mass spectrometry to d...

Lipids are highly diverse in their composition, properties and distribution in different biological entities. We aim to establish the lipidomes of several insulin-sensitive tissues and to test their plasticity when divergent feeding regimens and lifestyles are imposed. Here, we report a proton nuclear magnetic resonance (1H-NMR) study of lipid abun...

Exercise is an effective strategy in the prevention and treatment of metabolic diseases. Alterations in the skeletal muscle proteome, including post-translational modifications, regulate its metabolic adaptations to exercise. Here, we examined the effect of high-intensity interval training (HIIT) on the proteome and acetylome of human skeletal musc...

Metabolic plasticity is the ability of a biological system to adapt its metabolic phenotype to different environmental stressors. We used a whole-body and tissue-specific phenotypic, functional, metabolomic and transcriptomic approach to systematically assess metabolic plasticity in diet-induced obese mice after a combined nutritional and exercise...

Mitochondrial respiratory complex subunits assemble in supercomplexes. Studies of supercomplexes have typically relied upon antibody-based protein quantification, often limited to the analysis of a single subunit per respiratory complex. To provide a deeper insight into mitochondrial and supercomplex plasticity, we combined Blue Native Polyacrylami...

Universal proteomics sample preparation is challenging because of the high heterogeneity of biological samples. Here we describe a novel mechanism that exploits the inherent instability of denatured proteins for nonspecific immobilization on microparticles by protein aggregation capture. To demonstrate the general applicability of this mechanism, w...

Universal proteomics sample preparation is challenging due to the high heterogeneity of biological samples. Here we describe a novel mechanism that exploits the inherent instability of denatured proteins for non-specific immobilization on microparticles by protein aggregation capture. To demonstrate the general applicability of this mechanism, we a...

Calorie restriction (CR) exerts remarkable, beneficial effects on glucose homeostasis by mechanisms that are not fully understood. Given the relevance of white adipose tissue (WAT) in glucose homeostasis, we aimed at identifying the main cellular processes regulated in WAT in response to CR in a pathologic context of obesity. For this, a gene‐expre...

Merging transcriptomics or metabolomics data remains insufficient for metabolic flux estimation. Ramirez et al. integrate a genome-scale metabolic model with extracellular flux data to predict and validate metabolic differences between white and brown adipose tissue. This method allows both metabolic phenotyping and the identification of potential...

After publication of the article [1], it has been brought to our attention that the full funding acknowledgement is missing from the original article. It should also include the following – “This work was supported by the Instituto de Salud Carlos III with FEDER funds (Otra forma de hacer Europa) from the European Commission (FIS: PI12/01823)”.

Insulin resistance precedes and predicts the onset of type 2 diabetes (T2D) in susceptible humans, underscoring its important role in the complex pathogenesis of this disease. Insulin resistance contributes to multiple tissue defects characteristic of T2D, including reduced insulin-stimulated glucose uptake in insulin-sensitive tissues, increased h...

Niemann Pick type C (NPC) disease is a progressive lysosomal storage disorder caused by mutations in genes encoding NPC1/NPC2 proteins, characterized by neurological defects, hepatosplenomegaly and premature death. While the primary biochemical feature of NPC disease is the intracellular accumulation of cholesterol and gangliosides, predominantly i...

Type 2 diabetes (T2D) is increasing worldwide, making identification of biomarkers for detection, staging, and effective prevention strategies an especially critical scientific and medical goal. Fortunately, advances in metabolomics techniques, together with improvements in bioinformatics and mathematical modeling approaches, have provided the scie...

Identifying markers of human insulin resistance may permit development of new approaches for treatment and prevention of type 2 diabetes. To this end, we analyzed the fasting plasma metabolome in metabolically characterized human volunteers across a spectrum of insulin resistance. We demonstrate that plasma betaine levels are reduced in insulin res...

Introduction: Mitochondria form an interconnected and dynamic web that undergoes continuous cycles of fusion and fission events. This phenomenon, known as mitochondrial dynamics, represents a key quality control system to maintain a healthy mitochondrial population but also a mechanism to bioenergetically adapt to the cellular and tissue energetic...

In brain inflammatory diseases, axonal damage is one of the most critical steps in the cascade that leads to permanent disability. Thus, identifying the initial events triggered by inflammation or oxidative stress that provoke axonal damage is critical for the development of neuroprotective therapies. Energy depletion due to mitochondrial dysfuncti...

Type 2 diabetes mellitus and metabolic syndrome are two highly prevalent clinical entities in our population and threaten to become a true pandemic. While there are still gaps in medical knowledge about the pathophysiological mechanisms leading to the development of both conditions, a significant effort has been made to study them in detail. Inflam...

Context: Diabetes is frequently diagnosed late, when the development of complications is almost inevitable, decreasing the quality of life of patients. However, early detection of affected individuals would allow the implementation of timely and effective therapies. Objective: Here we set to describe the profile of circulating microRNAs (miRNAs)...

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Mitofusin 2 (MFN2) plays critical roles in both mitochondrial fusion and the establishment of mitochondria-endoplasmic reticulum (ER) interactions. Hypothalamic ER stress has emerged as a causative factor for the development of leptin resistance, but the underlying mechanisms are largely unknown. Here, we show that mitochondria-ER contacts in anore...

http://www.mitophysiology.org/fileadmin/user_upload/MiP/MiP2013/MiPSummer2013-_Abstract_book.pdf