Maria Jimenez
University of Geneva
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Featured researches published by Maria Jimenez.
FEBS Letters | 2002
Maria Jimenez; Bertrand Léger; Kriss Canola; Lorenz Lehr; Patrizia Arboit; Josiane Seydoux; Aaron P. Russell; Jean-Paul Giacobino; Patrick Muzzin; Frédéric Preitner
Catecholamines are viewed as major stimulants of diet‐ and cold‐induced thermogenesis and of fasting‐induced lipolysis, through the β‐adrenoceptors (β1/β2/β3). To test this hypothesis, we generated β1/β2/β3‐adrenoceptor triple knockout (TKO) mice and compared them to wild type animals. TKO mice exhibited normophagic obesity and cold‐intolerance. Their brown fat had impaired morphology and lacked responses to cold of uncoupling protein‐1 expression. In contrast, TKO mice had higher circulating levels of free fatty acids and glycerol at basal and fasted states, suggesting enhanced lipolysis. Hence, β‐adrenergic signalling is essential for the resistance to obesity and cold, but not for the lipolytic response to fasting.
Diabetes | 2007
Eric Le Gouill; Maria Jimenez; Christophe Binnert; Pierre-Yves Jayet; Sébastien Thalmann; Pascal Nicod; Urs Scherrer; Peter Vollenweider
OBJECTIVE— Recent observations indicate that the delivery of nitric oxide by endothelial nitric oxide synthase (eNOS) is not only critical for metabolic homeostasis, but could also be important for mitochondrial biogenesis, a key organelle for free fatty acid (FFA) oxidation and energy production. Because mice deficient for the gene of eNOS (eNOS−/−) have increased triglycerides and FFA levels, in addition to hypertension and insulin resistance, we hypothesized that these knockout mice may have decreased energy expenditure and defective β-oxidation. RESEARCH DESIGN AND METHODS— Several markers of mitochondrial activity were assessed in C57BL/6J wild-type or eNOS−/− mice including the energy expenditure and oxygen consumption by indirect calorimetry, in vitro β-oxidation in isolated mitochondria from skeletal muscle, and expression of genes involved in fatty acid oxidation. RESULTS— eNOS−/− mice had markedly lower energy expenditure (−10%, P < 0.05) and oxygen consumption (−15%, P < 0.05) than control mice. This was associated with a roughly 30% decrease of the mitochondria content (P < 0.05) and, most importantly, with mitochondrial dysfunction, as evidenced by a markedly lower β-oxidation of subsarcolemmal mitochondria in skeletal muscle (−30%, P < 0.05). Finally, impaired mitochondrial β-oxidation was associated with a significant increase of the intramyocellular lipid content (30%, P < 0.05) in gastrocnemius muscle. CONCLUSIONS— These data indicate that elevated FFA and triglyceride in eNOS−/− mice result in defective mitochondrial β-oxidation in muscle cells.
Biochimica et Biophysica Acta | 2001
Ruben A. Simonyan; Maria Jimenez; Rolando B. Ceddia; Jean-Paul Giacobino; Patrick Muzzin; Vladimir P. Skulachev
The mechanism of thermoregulatory uncoupling of respiration and phosphorylation in skeletal muscles has been studied. It is found that 24 h cold exposure results in (i) a 3-fold increase in the amount of UCP3 protein in rat skeletal muscle mitochondria, and (ii) pronounced lowering of the membrane potential in isolated rat or mouse skeletal muscle mitochondria. The decrease in membrane potential is reversed by adding bovine serum albumin. Cold exposure is also found to sensitize the membrane potential to the uncoupling action of added fatty acid (laurate). After laurate addition, the recoupling effects of GDP and carboxyatractylate decrease whereas that of albumin increases in mitochondria from cold-treated rats or mice. Changes similar to those induced by cold can be initiated by the in vivo addition of thyroxine. Cold exposure does not affect energy coupling in liver mitochondria. The possible involvement of UCP3 isoforms in nucleotide-sensitive and -insensitive uncoupling is discussed.
FEBS Letters | 2006
Lorenz Lehr; Kriss Canola; Cedric Asensio; Maria Jimenez; Françoise Kuehne; Jean-Paul Giacobino; Patrick Muzzin
In rodent brown adipose tissue, the β‐adrenergic signaling is believed, by an action on PGC‐1α, to control UCP1 expression and mitochondriogenesis. We addressed this hypothesis using β1/β2/β3‐adrenoceptor knockout (β‐less) brown adipocytes in primary culture. In these cells: (a) proliferation and differentiation into multilocular cells were normal; (b) UCP1 mRNA expression was dramatically decreased (by 93%), whereas PGC‐1α and mtTFA mRNA expressions were not; (c) UCP1, PGC‐1α and COX IV protein expressions were decreased by 97%, 62% and 22%, respectively. Altogether the data show a dissociation between the control of UCP1, which is mostly β‐adrenoceptor‐dependent and that of PGC‐1α and of mitochondriogenesis which are not.
British Journal of Pharmacology | 2000
Jaap Oostendorp; Frédéric Preitner; James D Moffatt; Maria Jimenez; Jean Paul Giacobino; Peter C. M. Molenaar; Alberto J. Kaumann
The smooth muscle relaxant responses to the mixed β3‐, putative β4‐adrenoceptor agonist, (−)‐CGP 12177 in rat colon are partially resistant to blockade by the β3‐adrenoceptor antagonist SR59230A suggesting involvement of β3‐ and putative β4‐adrenoceptors. We now investigated the function of the putative β4‐adrenoceptor and other β‐adrenoceptor subtypes in the colon, oesophagus and ureter of wildtype (WT) and β3‐adrenoceptor knockout (β3KO) mice. (−)‐Noradrenaline and (−)‐adrenaline relaxed KCl (30 mM)‐precontracted colon mostly through β1‐and β3‐adrenoceptors to a similar extent and to a minor extent through β2‐adrenoceptors. In colon from β3KO mice, (−)‐noradrenaline was as potent as in WT mice but the effects were mediated entirely through β1‐adrenoceptors. (−)‐CGP 12177 relaxed colon from β3KO mice with 2 fold greater potency than in WT mice. The maintenance of potency for (−)‐noradrenaline and increase for (−)‐CGP 12177 indicate compensatory increases in β1‐ and putative β4‐adrenoceptor function in β3KO mice. In oesophagi precontracted with 1 μM carbachol, (−)‐noradrenaline caused relaxation mainly through β1‐and β3‐adrenoceptors. (−)‐CGP 12177 (2 μM) relaxed oesophagi from WT by 61.4±5.1% and β3KO by 67.3±10.1% of the (−)‐isoprenaline‐evoked relaxation, consistent with mediation through putative β4‐adrenoceptors. In ureter, (−)‐CGP 12177 (2 μM) reduced pacemaker activity by 31.1±2.3% in WT and 31.3±7.5% in β3KO, consistent with mediation through putative β4‐adrenoceptors. Relaxation of mouse colon and oesophagus by catecholamines are mediated through β1‐ and β3‐adrenoceptors in WT. The putative β4‐adrenoceptor, which presumably is an atypical state of the β1‐adrenoceptor, mediates the effects of (−)‐CGP 12177 in colon, oesophagus and ureter.
Pflügers Archiv: European Journal of Physiology | 2006
Christoph Ziskoven; Sabrina Grafweg; Birgit Bölck; Rudolf J. Wiesner; Maria Jimenez; Jean-Paul Giacobino; Wilhelm Bloch; Robert H. G. Schwinger; Klara Brixius
This study investigated the influence of chronic β3-adrenoceptor deficiency on myocardial function. Therefore, we investigated Ca2+-regulatory proteins, SERCA 2a activity, and myofibrillar and mitochondrial function in hearts of wild-type (WT, n=7) and β3-adrenoceptor knockout mice (β3-KNO, n=7). Morphometric heart analysis showed no difference between WT and β3-KNO. No alterations were observed for the protein expression of the ryanodine receptor or phospholamban. However, in β3-KNO mice, protein expression of SERCA 2a and phospholamban phosphorylation were significantly increased. These changes were accompanied by an increased SERCA 2a activity in β3-KNO. Alterations in phospholamban phosphorylation were independent of alterations in β1/β2-adrenoceptor distribution and protein expression of G proteins in β3-KNO. Measurement of myofibrillar Ca2+ sensitivity showed no difference in the Ca2+/force relation for WT and β3-KNO. The same seems to hold true for mitochondrial function since the protein expressions of cytochrome c, uncoupling protein 3 and cytochrome c oxidase subunit IV were similar in WT and β3-KNO. The conclusion is that depression of β3-adrenergic stimulation may modulate the protein expression of SERCA 2a and phospholamban phosphorylation, thereby improving sarcoplasmic reticulum Ca2+ uptake. Thus, β3-adrenergic depression may be a therapeutic aim in situations of impaired SERCA 2a activity, e.g. for the treatment of heart failure.
FEBS Letters | 2004
Lorenz Lehr; Françoise Kuehne; Patrizia Arboit; Jean-Paul Giacobino; Francis Poulin; Patrick Muzzin; Maria Jimenez
Knockout of the translation inhibitor 4E‐BP1 induces an overexpression of uncoupling protein‐1 (UCP1) [Nature Medicine 7 (2001) 1128]. A possible inverse control of UCP1 and 4E‐BP1 expressions in mouse brown adipose tissue was investigated. Cold‐exposure, which increases the expression of UCP1, decreased that of 4E‐BP1 mRNA in wild type but not in β1/β2/β3‐adrenoceptor knockout mice. Administration of the β3‐adrenoceptor agonist CL 316 246 decreased 4E‐BP1 mRNA by 75% and protein by 41% after 6 and 48 h, respectively. Our data are the first report of a regulation by the β3‐adrenoceptor of 4E‐BP1 expression. They support a role of the latter in adaptive thermogenesis.
FEBS Journal | 2003
Maria Jimenez; Giorgio Barbatelli; Roberta Allevi; Saverio Cinti; Josiane Seydoux; Jean-Paul Giacobino; Patrick Muzzin; Frédéric Preitner
FEBS Journal | 2002
Maria Jimenez; Cédric Yvon; Lorenz Lehr; Bertrand Léger; Patrick A. Keller; Aaron P. Russell; Françoise Kühne; Pierre Flandin; Jean-Paul Giacobino; Patrick Muzzin
Diabetes | 2005
Cedric Asensio; Maria Jimenez; Françoise Kühne; Françoise Rohner-Jeanrenaud; Patrick Muzzin