Publications by authors named "Aurélie Batut"

16 Publications

  • Page 1 of 1

Lipid exchanges drove the evolution of mutualism during plant terrestrialization.

Science 2021 05;372(6544):864-868

Laboratoire de Recherche en Sciences Végétales (LRSV), Université de Toulouse, CNRS, UPS, 31326 Castanet-Tolosan, France.

Symbiosis with arbuscular mycorrhizal fungi (AMF) improves plant nutrition in most land plants, and its contribution to the colonization of land by plants has been hypothesized. Here, we identify a conserved transcriptomic response to AMF among land plants, including the activation of lipid metabolism. Using gain of function, we show the transfer of lipids from the liverwort to AMF and its direct regulation by the transcription factor WRINKLED (WRI). Arbuscules, the nutrient-exchange structures, were not formed in loss-of-function mutants in , leading to aborted mutualism. Our results show the orthology of the symbiotic transfer of lipids across land plants and demonstrate that mutualism with arbuscular mycorrhizal fungi was present in the most recent ancestor of land plants 450 million years ago.
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http://dx.doi.org/10.1126/science.abg0929DOI Listing
May 2021

Integrative study of diet-induced mouse models of NAFLD identifies PPARα as a sexually dimorphic drug target.

Gut 2021 Apr 26. Epub 2021 Apr 26.

Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), UMR1297, INSERM/UPS, Université de Toulouse, Toulouse, France.

Objective: We evaluated the influence of sex on the pathophysiology of non-alcoholic fatty liver disease (NAFLD). We investigated diet-induced phenotypic responses to define sex-specific regulation between healthy liver and NAFLD to identify influential pathways in different preclinical murine models and their relevance in humans.

Design: Different models of diet-induced NAFLD (high-fat diet, choline-deficient high-fat diet, Western diet or Western diet supplemented with fructose and glucose in drinking water) were compared with a control diet in male and female mice. We performed metabolic phenotyping, including plasma biochemistry and liver histology, untargeted large-scale approaches (liver metabolome, lipidome and transcriptome), gene expression profiling and network analysis to identify sex-specific pathways in the mouse liver.

Results: The different diets induced sex-specific responses that illustrated an increased susceptibility to NAFLD in male mice. The most severe lipid accumulation and inflammation/fibrosis occurred in males receiving the high-fat diet and Western diet, respectively. Sex-biased hepatic gene signatures were identified for these different dietary challenges. The peroxisome proliferator-activated receptor α (PPARα) co-expression network was identified as sexually dimorphic, and in vivo experiments in mice demonstrated that hepatocyte PPARα determines a sex-specific response to fasting and treatment with pemafibrate, a selective PPARα agonist. Liver molecular signatures in humans also provided evidence of sexually dimorphic gene expression profiles and the sex-specific co-expression network for PPARα.

Conclusions: These findings underscore the sex specificity of NAFLD pathophysiology in preclinical studies and identify PPARα as a pivotal, sexually dimorphic, pharmacological target.

Trial Registration Number: NCT02390232.
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http://dx.doi.org/10.1136/gutjnl-2020-323323DOI Listing
April 2021

Ghrelin uses the GHS-R1a/Gi/cAMP pathway and induces differentiation only in mature osteoblasts. This ghrelin pathway is impaired in AIS patients.

Biochem Biophys Rep 2020 Dec 11;24:100782. Epub 2020 Sep 11.

INSERM, UMR1043, Centre de Physiopathologie de Toulouse Purpan, CHU Toulouse, France.

We have examined the Acylated Ghrelin (AG)/Gi pathway in different human osteoblastic cell lines. We have found that: 1) AG induces differentiation/mineralization only in mature osteoblasts; 2) the expression of GHS-R1a increases up to the mature cell stage, 3) the action is mediated via the GHS-R/Gi/cAMP pathway only in mature osteoblasts, and 4) osteoblastic cells from adolescent idiopathic scoliosis (AIS) are resistant to the AG/Gi/cAMP pathway. Altogether, these results suggested that AG uses the GHS-R1a/Gi/cAMP pathway to induce differentiation in mature osteoblasts only. This pathway is impaired in AIS osteoblasts. Understanding AG-specific pathways involved in normal and pathological osteoblasts may be useful for developing new treatments for pathologies such as AIS or osteoporosis.
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http://dx.doi.org/10.1016/j.bbrep.2020.100782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494670PMC
December 2020

An Optimized Dual Extraction Method for the Simultaneous and Accurate Analysis of Polar Metabolites and Lipids Carried out on Single Biological Samples.

Metabolites 2020 Aug 19;10(9). Epub 2020 Aug 19.

MetaboHUB-MetaToul-Lipidomics Core Facility, Inserm U1048, 31432 Toulouse, France.

The functional understanding of metabolic changes requires both a significant investigation into metabolic pathways, as enabled by global metabolomics and lipidomics approaches, and the comprehensive and accurate exploration of specific key pathways. To answer this pivotal challenge, we propose an optimized approach, which combines an efficient sample preparation, aiming to reduce the variability, with a biphasic extraction method, where both the aqueous and organic phases of the same sample are used for mass spectrometry analyses. We demonstrated that this double extraction protocol allows working with one single sample without decreasing the metabolome and lipidome coverage. It enables the targeted analysis of 40 polar metabolites and 82 lipids, together with the absolute quantification of 32 polar metabolites, providing comprehensive coverage and quantitative measurement of the metabolites involved in central carbon energy pathways. With this method, we evidenced modulations of several lipids, amino acids, and energy metabolites in HepaRG cells exposed to fenofibrate, a model hepatic toxicant, and metabolic modulator. This new protocol is particularly relevant for experiments involving limited amounts of biological material and for functional metabolic explorations and is thus of particular interest for studies aiming to decipher the effects and modes of action of metabolic disrupting compounds.
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http://dx.doi.org/10.3390/metabo10090338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570216PMC
August 2020

Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites.

Nat Commun 2020 08 13;11(1):4056. Epub 2020 Aug 13.

Cancer Research Center of Toulouse (CRCT), INSERM U1037, CNRS ERL5294, University of Toulouse, Toulouse, France.

Autophagy has been associated with oncogenesis with one of its emerging key functions being its contribution to the metabolism of tumors. Therefore, deciphering the mechanisms of how autophagy supports tumor cell metabolism is essential. Here, we demonstrate that the inhibition of autophagy induces an accumulation of lipid droplets (LD) due to a decrease in fatty acid β-oxidation, that leads to a reduction of oxidative phosphorylation (OxPHOS) in acute myeloid leukemia (AML), but not in normal cells. Thus, the autophagic process participates in lipid catabolism that supports OxPHOS in AML cells. Interestingly, the inhibition of OxPHOS leads to LD accumulation with the concomitant inhibition of autophagy. Mechanistically, we show that the disruption of mitochondria-endoplasmic reticulum (ER) contact sites (MERCs) phenocopies OxPHOS inhibition. Altogether, our data establish that mitochondria, through the regulation of MERCs, controls autophagy that, in turn finely tunes lipid degradation to fuel OxPHOS supporting proliferation and growth in leukemia.
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http://dx.doi.org/10.1038/s41467-020-17882-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426880PMC
August 2020

Adipocyte Fatty Acid Transfer Supports Megakaryocyte Maturation.

Cell Rep 2020 07;32(1):107875

INSERM U1048 and Paul Sabatier University, Institute of Cardiovascular and Metabolic Diseases, Toulouse, France. Electronic address:

Megakaryocytes (MKs) come from a complex process of hematopoietic progenitor maturation within the bone marrow that gives rise to de novo circulating platelets. Bone marrow microenvironment contains a large number of adipocytes with a still ill-defined role. This study aims to analyze the influence of adipocytes and increased medullar adiposity in megakaryopoiesis. An in vivo increased medullar adiposity in mice caused by high-fat-diet-induced obesity is associated to an enhanced MK maturation and proplatelet formation. In vitro co-culture of adipocytes with bone marrow hematopoietic progenitors shows that delipidation of adipocytes directly supports MK maturation by enhancing polyploidization, amplifying the demarcation membrane system, and accelerating proplatelet formation. This direct crosstalk between adipocytes and MKs occurs through adipocyte fatty acid transfer to MKs involving CD36 to reinforce megakaryocytic maturation. Thus, these findings unveil an influence of adiposity on MK homeostasis based on a dialogue between adipocytes and MKs.
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http://dx.doi.org/10.1016/j.celrep.2020.107875DOI Listing
July 2020

Hepatocyte-specific deletion of Pparα promotes NAFLD in the context of obesity.

Sci Rep 2020 04 16;10(1):6489. Epub 2020 Apr 16.

Toxalim, INRAE UMR 1331, ENVT, INP-Purpan, University of Toulouse, Paul Sabatier University, F-31027, Toulouse, France.

Peroxisome proliferator activated receptor α (PPARα) acts as a fatty acid sensor to orchestrate the transcription of genes coding for rate-limiting enzymes required for lipid oxidation in hepatocytes. Mice only lacking Pparα in hepatocytes spontaneously develop steatosis without obesity in aging. Steatosis can develop into non alcoholic steatohepatitis (NASH), which may progress to irreversible damage, such as fibrosis and hepatocarcinoma. While NASH appears as a major public health concern worldwide, it remains an unmet medical need. In the current study, we investigated the role of hepatocyte PPARα in a preclinical model of steatosis. For this, we used High Fat Diet (HFD) feeding as a model of obesity in C57BL/6 J male Wild-Type mice (WT), in whole-body Pparα deficient mice (Pparα) and in mice lacking Pparα only in hepatocytes (Pparα). We provide evidence that Pparα deletion in hepatocytes promotes NAFLD and liver inflammation in mice fed a HFD. This enhanced NAFLD susceptibility occurs without development of glucose intolerance. Moreover, our data reveal that non-hepatocytic PPARα activity predominantly contributes to the metabolic response to HFD. Taken together, our data support hepatocyte PPARα as being essential to the prevention of NAFLD and that extra-hepatocyte PPARα activity contributes to whole-body lipid homeostasis.
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http://dx.doi.org/10.1038/s41598-020-63579-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162950PMC
April 2020

Improving lipid mapping in Genome Scale Metabolic Networks using ontologies.

Metabolomics 2020 03 25;16(4):44. Epub 2020 Mar 25.

UMR1331, Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31300, Toulouse, France.

Introduction: To interpret metabolomic and lipidomic profiles, it is necessary to identify the metabolic reactions that connect the measured molecules. This can be achieved by putting them in the context of genome-scale metabolic network reconstructions. However, mapping experimentally measured molecules onto metabolic networks is challenging due to differences in identifiers and level of annotation between data and metabolic networks, especially for lipids.

Objectives: To help linking lipids from lipidomics datasets with lipids in metabolic networks, we developed a new matching method based on the ChEBI ontology. The implementation is freely available as a python library and in MetExplore webserver.

Methods: Our matching method is more flexible than an exact identifier-based correspondence since it allows establishing a link between molecules even if a different level of precision is provided in the dataset and in the metabolic network. For instance, it can associate a generic class of lipids present in the network with the molecular species detailed in the lipidomics dataset. This mapping is based on the computation of a distance between molecules in ChEBI ontology.

Results: We applied our method to a chemical library (968 lipids) and an experimental dataset (32 modulated lipids) and showed that using ontology-based mapping improves and facilitates the link with genome scale metabolic networks. Beyond network mapping, the results provide ways for improvements in terms of network curation and lipidomics data annotation.

Conclusion: This new method being generic, it can be applied to any metabolomics data and therefore improve our comprehension of metabolic modulations.
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http://dx.doi.org/10.1007/s11306-020-01663-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096385PMC
March 2020

Bis(monoacylglycero)phosphate regulates oxysterol binding protein-related protein 11 dependent sterol trafficking.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 09 25;1864(9):1247-1257. Epub 2019 May 25.

Inserm, U1060, CarMeN Laboratory, Villeurbanne, France; INSA-Lyon, Villeurbanne, France. Electronic address:

Bis(Monoacylglycero) Phosphate (BMP) is a unique phospholipid localized in late endosomes, a critical cellular compartment in low density lipoprotein (LDL)-cholesterol metabolism. In previous work, we demonstrated the important role of BMP in the regulation of macrophage cholesterol homeostasis. BMP exerts a protective role against the pro-apoptotic effect of oxidized LDL (oxLDL) by reducing the production of deleterious oxysterols. As the intracellular sterol traffic in macrophages is in part regulated by oxysterol binding protein (OSBP) and OSBP-related proteins (ORPs), we investigated the role of ORP11, localized at the Golgi-late endosomes interface, in the BMP-mediated protection from oxLDL/oxysterol cytotoxicity. Stably silencing of ORP11 in mouse RAW264.7 macrophages via a shRNA lentiviruses system had no effect on BMP production. However, ORP11 knockdown abrogated the protective action of BMP against oxLDL induced apoptosis. In oxLDL treated control cells, BMP enrichment was associated with reduced generation of 7-oxysterols, while these oxysterol species were abundant in the ORP11 knock-down cells. Of note, BMP enrichment in ORP11 knock-down cells was associated with a drastic increase in free cholesterol and linked to a decrease of cholesterol efflux. The expression of ATP-binding cassette-transporter G1 (ABCG1) was also reduced in the ORP11 knock-down cells. These observations demonstrate a cooperative function of OPR11 and BMP, in intracellular cholesterol trafficking in cultured macrophages. We suggest that BMP favors the egress of cholesterol from late endosomes via an ORP11-dependent mechanism, resulting in a reduced production of cytotoxic 7-oxysterols.
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http://dx.doi.org/10.1016/j.bbalip.2019.05.011DOI Listing
September 2019

Stable Isotope Labeling Highlights Enhanced Fatty Acid and Lipid Metabolism in Human Acute Myeloid Leukemia.

Int J Mol Sci 2018 Oct 25;19(11). Epub 2018 Oct 25.

Université de Toulouse, 31000 Toulouse, France.

: In Acute Myeloid Leukemia (AML), a complete response to chemotherapy is usually obtained after conventional chemotherapy but overall patient survival is poor due to highly frequent relapses. As opposed to chronic myeloid leukemia, B lymphoma or multiple myeloma, AML is one of the rare malignant hemopathies the therapy of which has not significantly improved during the past 30 years despite intense research efforts. One promising approach is to determine metabolic dependencies in AML cells. Moreover, two key metabolic enzymes, isocitrate dehydrogenases (IDH1/2), are mutated in more than 15% of AML patient, reinforcing the interest in studying metabolic reprogramming, in particular in this subgroup of patients. : Using a multi-omics approach combining proteomics, lipidomics, and isotopic profiling of [U-C] glucose and [U-C] glutamine cultures with more classical biochemical analyses, we studied the impact of the IDH1 R132H mutation in AML cells on lipid biosynthesis. : Global proteomic and lipidomic approaches showed a dysregulation of lipid metabolism, especially an increase of phosphatidylinositol, sphingolipids (especially few species of ceramide, sphingosine, and sphinganine), free cholesterol and monounsaturated fatty acids in IDH1 mutant cells. Isotopic profiling of fatty acids revealed that higher lipid anabolism in IDH1 mutant cells corroborated with an increase in lipogenesis fluxes. : This integrative approach was efficient to gain insight into metabolism and dynamics of lipid species in leukemic cells. Therefore, we have determined that lipid anabolism is strongly reprogrammed in IDH1 mutant AML cells with a crucial dysregulation of fatty acid metabolism and fluxes, both being mediated by 2-HG (2-Hydroxyglutarate) production.
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http://dx.doi.org/10.3390/ijms19113325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274868PMC
October 2018

The exerkine apelin reverses age-associated sarcopenia.

Nat Med 2018 09 30;24(9):1360-1371. Epub 2018 Jul 30.

Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048, Université de Toulouse, Université Paul Sabatier, Toulouse, France.

Sarcopenia, the degenerative loss of skeletal muscle mass, quality and strength, lacks early diagnostic tools and new therapeutic strategies to prevent the frailty-to-disability transition often responsible for the medical institutionalization of elderly individuals. Herein we report that production of the endogenous peptide apelin, induced by muscle contraction, is reduced in an age-dependent manner in humans and rodents and is positively associated with the beneficial effects of exercise in older persons. Mice deficient in either apelin or its receptor (APLNR) presented dramatic alterations in muscle function with increasing age. Various strategies that restored apelin signaling during aging further demonstrated that this peptide considerably enhanced muscle function by triggering mitochondriogenesis, autophagy and anti-inflammatory pathways in myofibers as well as enhancing the regenerative capacity by targeting muscle stem cells. Taken together, these findings revealed positive regulatory feedback between physical activity, apelin and muscle function and identified apelin both as a tool for diagnosis of early sarcopenia and as the target of an innovative pharmacological strategy to prevent age-associated muscle weakness and restore physical autonomy.
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http://dx.doi.org/10.1038/s41591-018-0131-6DOI Listing
September 2018

Chronic apelin treatment improves hepatic lipid metabolism in obese and insulin-resistant mice by an indirect mechanism.

Endocrine 2018 04 1;60(1):112-121. Epub 2018 Feb 1.

Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048, Toulouse, France.

Purpose: Apelin treatment has been shown to improve insulin sensitivity in insulin resistant mice by acting in skeletal muscles. However, the effects of systemic apelin on the hepatic energy metabolism have not been addressed. We thus aimed to determine the effect of chronic apelin treatment on the hepatic lipid metabolism in insulin resistant mice. The apelin receptor (APJ) expression was also studied in this context since its regulation has only been reported in severe liver pathologies.

Methods: Mice were fed a high-fat diet (HFD) in order to become obese and insulin resistant compared to chow fed mice (CD). HFD mice then received a daily intraperitoneal injection of apelin (0.1 µmol/kg) or PBS during 28 days.

Results: Triglycerides content and the expression of different lipogenesis-related genes were significantly decreased in the liver of HFD apelin-treated compared to PBS-treated mice. Moreover, at this stage of insulin resistance, the beta-oxidation was increased in liver homogenates of HFD PBS-treated mice compared to CD mice and reduced in HFD apelin-treated mice. Finally, APJ expression was not up-regulated in the liver of insulin resistant mice. In isolated hepatocytes from chow and HFD fed mice, apelin did not induce significant effect.

Conclusions: Altogether, these results suggest that systemic apelin treatment decreases steatosis in insulin resistant mice without directly targeting hepatocytes.
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http://dx.doi.org/10.1007/s12020-018-1536-1DOI Listing
April 2018

Insights into the role of hepatocyte PPARα activity in response to fasting.

Mol Cell Endocrinol 2018 08 31;471:75-88. Epub 2017 Jul 31.

Institut National de La Recherche Agronomique (INRA), UMR1331 ToxAlim, Toulouse, France; Institut National de La Santé et de La Recherche Médicale (INSERM), UMR1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France. Electronic address:

The liver plays a central role in the regulation of fatty acid metabolism. Hepatocytes are highly sensitive to nutrients and hormones that drive extensive transcriptional responses. Nuclear hormone receptors are key transcription factors involved in this process. Among these factors, PPARα is a critical regulator of hepatic lipid catabolism during fasting. This study aimed to analyse the wide array of hepatic PPARα-dependent transcriptional responses during fasting. We compared gene expression in male mice with a hepatocyte specific deletion of PPARα and their wild-type littermates in the fed (ad libitum) and 24-h fasted states. Liver samples were acquired, and transcriptome and lipidome analyses were performed. Our data extended and confirmed the critical role of hepatocyte PPARα as a central for regulator of gene expression during starvation. Interestingly, we identified novel PPARα-sensitive genes, including Cxcl-10, Rab30, and Krt23. We also found that liver phospholipid remodelling was a novel fasting-sensitive pathway regulated by PPARα. These results may contribute to investigations on transcriptional control in hepatic physiology and underscore the clinical relevance of drugs that target PPARα in liver pathologies, such as non-alcoholic fatty liver disease.
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http://dx.doi.org/10.1016/j.mce.2017.07.035DOI Listing
August 2018

Central chronic apelin infusion decreases energy expenditure and thermogenesis in mice.

Sci Rep 2016 08 23;6:31849. Epub 2016 Aug 23.

Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Université Paul Sabatier, UPS, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), CHU Rangueil, 1 Avenue Jean Poulhès, BP84225, 31432 Toulouse Cedex 4, France.

Apelin is a bioactive peptide involved in the control of energy metabolism. In the hypothalamus, chronic exposure to high levels of apelin is associated with an increase in hepatic glucose production, and then contributes to the onset of type 2 diabetes. However, the molecular mechanisms behind deleterious effects of chronic apelin in the brain and consequences on energy expenditure and thermogenesis are currently unknown. We aimed to evaluate the effects of chronic intracerebroventricular (icv) infusion of apelin in normal mice on hypothalamic inflammatory gene expression, energy expenditure, thermogenesis and brown adipose tissue functions. We have shown that chronic icv infusion of apelin increases the expression of pro-inflammatory factors in the hypothalamus associated with an increase in plasma interleukin-1 beta. In parallel, mice infused with icv apelin exhibit a significant lower energy expenditure coupled to a decrease in PGC1alpha, PRDM16 and UCP1 expression in brown adipose tissue which could explain the alteration of thermogenesis in these mice. These data provide compelling evidence that central apelin contributes to the development of type 2 diabetes by altering energy expenditure, thermogenesis and fat browning.
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http://dx.doi.org/10.1038/srep31849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994119PMC
August 2016

LEOPARD syndrome-associated SHP2 mutation confers leanness and protection from diet-induced obesity.

Proc Natl Acad Sci U S A 2014 Oct 6;111(42):E4494-503. Epub 2014 Oct 6.

Institut National de la Santé et de la Recherche Médicale, U1048, F-31432 Toulouse, France; Institut des Maladies Métaboliques et Cardiovasculaires, Université de Toulouse, Université Paul Sabatier, F-31432 Toulouse, France;

LEOPARD syndrome (multiple Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retardation of growth, sensorineural Deafness; LS), also called Noonan syndrome with multiple lentigines (NSML), is a rare autosomal dominant disorder associating various developmental defects, notably cardiopathies, dysmorphism, and short stature. It is mainly caused by mutations of the PTPN11 gene that catalytically inactivate the tyrosine phosphatase SHP2 (Src-homology 2 domain-containing phosphatase 2). Besides its pleiotropic roles during development, SHP2 plays key functions in energetic metabolism regulation. However, the metabolic outcomes of LS mutations have never been examined. Therefore, we performed an extensive metabolic exploration of an original LS mouse model, expressing the T468M mutation of SHP2, frequently borne by LS patients. Our results reveal that, besides expected symptoms, LS animals display a strong reduction of adiposity and resistance to diet-induced obesity, associated with overall better metabolic profile. We provide evidence that LS mutant expression impairs adipogenesis, triggers energy expenditure, and enhances insulin signaling, three features that can contribute to the lean phenotype of LS mice. Interestingly, chronic treatment of LS mice with low doses of MEK inhibitor, but not rapamycin, resulted in weight and adiposity gains. Importantly, preliminary data in a French cohort of LS patients suggests that most of them have lower-than-average body mass index, associated, for tested patients, with reduced adiposity. Altogether, these findings unravel previously unidentified characteristics for LS, which could represent a metabolic benefit for patients, but may also participate to the development or worsening of some traits of the disease. Beyond LS, they also highlight a protective role of SHP2 global LS-mimicking modulation toward the development of obesity and associated disorders.
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http://dx.doi.org/10.1073/pnas.1406107111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210352PMC
October 2014

Effects of dietary eicosapentaenoic acid (EPA) supplementation in high-fat fed mice on lipid metabolism and apelin/APJ system in skeletal muscle.

PLoS One 2013 7;8(11):e78874. Epub 2013 Nov 7.

Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Toulouse, Cedex 4, France ; Université de Toulouse, UPS, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France.

Various studies have shown that eicosapentaenoic acid (EPA) has beneficial effects on obesity and associated disorders. Apelin, the ligand of APJ receptor also exerts insulin-sensitizing effects especially by improving muscle metabolism. EPA has been shown to increase apelin production in adipose tissue but its effects in muscle have not been addressed. Thus, the effects of EPA supplementation (36 g/kg EPA) in high-fat diet (HFD) (45% fat, 20% protein, 35% carbohydrate) were studied in mice with focus on muscle lipid metabolism and apelin/APJ expression. Compared with HFD mice, HFD+EPA mice had significantly less weight gain, fat mass, lower blood glucose, insulinemia and hepatic steatosis after 10 weeks of diet. In addition, EPA prevented muscle metabolism alterations since intramuscular triglycerides were decreased and β-oxidation increased. In soleus muscles of HFD+EPA mice, apelin and APJ expression were significantly increased compared to HFD mice. However, plasma apelin concentrations in HFD and HFD+EPA mice were similar. EPA-induced apelin expression was confirmed in differentiated C2C12 myocytes but in this model, apelin secretion was also increased in response to EPA treatment. In conclusion, EPA supplementation in HFD prevents obesity and metabolic alterations in mice, especially in skeletal muscle. Since EPA increases apelin/APJ expression in muscle, apelin may act in a paracrine/autocrine manner to contribute to these benefical effects.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0078874PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820669PMC
August 2014
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