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  1. AU="Monnier, Chloe"
  2. AU="Marie Gilbert" AU="Marie Gilbert"
  3. AU="Soriano, Daniel"
  4. AU="Lai, Bryan K"
  5. AU="Metzner, K"
  6. AU=Spjeldnaes Amanda Hylland
  7. AU="Lin, Zhangya"
  8. AU="Jorge Pereira, B"
  9. AU=Kamps Frederik S.
  10. AU="Sowińska-Baranowska, Anna"
  11. AU="Štefek, Milan"
  12. AU="El Khatib, Mohammad"
  13. AU="Puccioni, Caterina"
  14. AU="Kostopoulos, Ioannis"
  15. AU=Kumar Adarsh
  16. AU="Millar, Amanda"
  17. AU="da Cruz Perez, Danyel Elias"
  18. AU="Henry des Tureaux, Thierry"
  19. AU="Mária Bucová"
  20. AU="Darling, Corbin"
  21. AU="Rosenthal, Philip"
  22. AU="Farley, John M B"
  23. AU="Longo, Lauren O"
  24. AU="Ogawa, Kumiko"
  25. AU="Min Gyu Lee"

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  1. Artikel ; Online: The nuclear retinoid-related orphan receptor RORα controls circadian thermogenic programming in white fat depots.

    Monnier, Chloé / Auclair, Martine / Le Cam, Gala / Garcia, Marie-Pauline / Antoine, Bénédicte

    Physiological reports

    2018  Band 6, Heft 8, Seite(n) e13678

    Abstract: The RORα-deficient staggerer (sg/sg) mouse is lean and resistant to diet-induced obesity. Its thermogenic activity was shown to be increased not only in brown adipose tissue (BAT), but also in subcutaneous white adipose tissue (WAT) where UCP1 content ... ...

    Abstract The RORα-deficient staggerer (sg/sg) mouse is lean and resistant to diet-induced obesity. Its thermogenic activity was shown to be increased not only in brown adipose tissue (BAT), but also in subcutaneous white adipose tissue (WAT) where UCP1 content was enhanced, however, without Prdm16 coexpression. Our observation of partial multilocular lipid morphology of WAT in sg/sg mice both in the inguinal and perigonadal sites led us to focus on the phenotype of both fat depots. Because RORα is a nuclear factor acting in the clock machinery, we looked at the circadian expression profile of genes involved in thermogenesis and browning in WAT and BAT depots of sg/sg and WT mice, through real-time quantitative PCR and western blotting. This 24-h period approach revealed both a rhythmic expression of thermogenic genes in WAT and an increased browning of all the WAT depots tested in sg/sg mice that indeed involved the canonical browning process (through induction of Pgc-1α and Prdm16). This was associated with an enhanced isoproterenol-induced oxygen consumption rate of WAT explants from sg/sg mice, which was reproducible in WT explants by treatment with a RORα inverse agonist SR 3335, that induced a parallel increase in the UCP1 protein. Inhibitors of browning differentiation, such as TLE3 and RIP140, could be new targets of RORα that would be rather implicated in the whitening of adipocytes. Our study showed the pivotal role of RORα as an inhibitor of the thermogenic program in WAT, the role that could be counteracted in vivo with the RORα antagonists currently in development.
    Mesh-Begriff(e) Adipocytes/metabolism ; Adipose Tissue, White/metabolism ; Animals ; Circadian Rhythm/physiology ; Energy Metabolism/physiology ; Mice ; Mice, Knockout ; Nuclear Receptor Subfamily 1, Group F, Member 1/genetics ; Nuclear Receptor Subfamily 1, Group F, Member 1/metabolism ; Thermogenesis/physiology
    Chemische Substanzen Nuclear Receptor Subfamily 1, Group F, Member 1
    Sprache Englisch
    Erscheinungsdatum 2018-04-19
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2724325-4
    ISSN 2051-817X ; 2051-817X
    ISSN (online) 2051-817X
    ISSN 2051-817X
    DOI 10.14814/phy2.13678
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: Phosphatidylinositol-4,5-Bisphosphate Binding to Amphiphysin-II Modulates T-Tubule Remodeling: Implications for Heart Failure.

    Zhou, Junlan / Singh, Neha / Monnier, Chloe / Marszalec, William / Gao, Li / Jin, Jing / Frisk, Michael / Louch, William E / Verma, Suresh / Krishnamurthy, Prasanna / Nico, Elsa / Mulla, Maaz / Aistrup, Gary L / Kishore, Raj / Wasserstrom, J Andrew

    Frontiers in physiology

    2021  Band 12, Seite(n) 782767

    Abstract: BIN1 (amphyphysin-II) is a structural protein involved in T-tubule (TT) formation and phosphatidylinositol-4,5-bisphosphate (PIP2) is responsible for localization of BIN1 to sarcolemma. The goal of this study was to determine if PIP2-mediated targeting ... ...

    Abstract BIN1 (amphyphysin-II) is a structural protein involved in T-tubule (TT) formation and phosphatidylinositol-4,5-bisphosphate (PIP2) is responsible for localization of BIN1 to sarcolemma. The goal of this study was to determine if PIP2-mediated targeting of BIN1 to sarcolemma is compromised during the development of heart failure (HF) and is responsible for TT remodeling. Immunohistochemistry showed co-localization of BIN1, Cav1.2, PIP2, and phospholipase-Cβ1 (PLCβ1) in TTs in normal rat and human ventricular myocytes. PIP2 levels were reduced in spontaneously hypertensive rats during HF progression compared to age-matched controls. A PIP Strip assay of two native mouse cardiac-specific isoforms of BIN1 including the longest (cardiac BIN1 #4) and shortest (cardiac BIN1 #1) isoforms as well human skeletal BIN1 showed that all bound PIP2. In addition, overexpression of all three BIN1 isoforms caused tubule formation in HL-1 cells. A triple-lysine motif in a short loop segment between two helices was mutated and replaced by negative charges which abolished tubule formation, suggesting a possible location for PIP2 interaction aside from known consensus binding sites. Pharmacological PIP2 depletion in rat ventricular myocytes caused TT loss and was associated with changes in Ca
    Sprache Englisch
    Erscheinungsdatum 2021-12-23
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2021.782767
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: The nuclear retinoid-related orphan receptor-α regulates adipose tissue glyceroneogenesis in addition to hepatic gluconeogenesis.

    Kadiri, Sarah / Monnier, Chloé / Ganbold, Munkhzul / Ledent, Tatiana / Capeau, Jacqueline / Antoine, Bénédicte

    American journal of physiology. Endocrinology and metabolism

    2015  Band 309, Heft 2, Seite(n) E105–14

    Abstract: Circadian rhythms have an essential role in feeding behavior and metabolism. RORα is a nuclear receptor involved in the interface of the circadian system and metabolism. The adipocyte glyceroneogenesis pathway derives free fatty acids (FFA) liberated by ... ...

    Abstract Circadian rhythms have an essential role in feeding behavior and metabolism. RORα is a nuclear receptor involved in the interface of the circadian system and metabolism. The adipocyte glyceroneogenesis pathway derives free fatty acids (FFA) liberated by lipolysis to reesterification into triglycerides, thus regulating FFA homeostasis and fat mass. Glyceroneogenesis shares with hepatic gluconeogenesis the key enzyme phosphoenolpyruvate carboxykinase c (PEPCKc), whose gene is a RORα target in the liver. RORα-deficient mice (staggerer, ROR(sg/sg)) have been shown to exhibit a lean phenotype and fasting hypoglycemia for unsolved reasons. In the present study, we investigated whether adipocyte glyceroneogenesis might also be a target pathway of RORα, and we further evaluated the role of RORα in hepatocyte gluconeogenesis. In vivo investigations comparing ROR(sg/sg) mice with their wild-type (WT) littermates under fasting conditions demonstrated that, in the absence of RORα, the release of FFA into the bloodstream was altered and the rise in glycemia in response to pyruvate reduced. The functional analysis of each pathway, performed in adipose tissue or liver explants, confirmed the impairment of adipocyte glyceroneogenesis and liver gluconeogenesis in the ROR(sg/sg) mice; these reductions of FFA reesterification or glucose production were associated with decreases in PEPCKc mRNA and protein levels. Treatment of explants with RORα agonist or antagonist enhanced or inhibited these pathways, respectively, in tissues isolated from WT but not ROR(sg/sg) mice. Our results indicated that both adipocyte glyceroneogenesis and hepatocyte gluconeogenesis were regulated by RORα. This study demonstrates the physiological function of RORα in regulating both glucose and FFA homeostasis.
    Mesh-Begriff(e) Adipose Tissue/drug effects ; Adipose Tissue/metabolism ; Animals ; Fatty Acids, Nonesterified/metabolism ; Gluconeogenesis/drug effects ; Gluconeogenesis/genetics ; Glucose/metabolism ; Glycerol/metabolism ; Lipid Metabolism/drug effects ; Lipid Metabolism/genetics ; Lipogenesis/drug effects ; Lipogenesis/genetics ; Liver/drug effects ; Liver/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nuclear Receptor Subfamily 1, Group F, Member 1/physiology
    Chemische Substanzen Fatty Acids, Nonesterified ; Nuclear Receptor Subfamily 1, Group F, Member 1 ; Rora protein, mouse ; Glucose (IY9XDZ35W2) ; Glycerol (PDC6A3C0OX)
    Sprache Englisch
    Erscheinungsdatum 2015-07-15
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603841-4
    ISSN 1522-1555 ; 0193-1849
    ISSN (online) 1522-1555
    ISSN 0193-1849
    DOI 10.1152/ajpendo.00518.2014
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Whole-body and adipose tissue-specific mechanisms underlying the metabolic effects of fibroblast growth factor 21 in the Siberian hamster.

    Lewis, Jo E / Monnier, Chloe / Marshall, Hayley / Fowler, Maxine / Green, Rebecca / Cooper, Scott / Chiotellis, Aristeidis / Luckett, Jeni / Perkins, Alan C / Coskun, Tamer / Adams, Andrew C / Samms, Ricardo J / Ebling, Francis J P / Tsintzas, Kostas

    Molecular metabolism

    2019  Band 31, Seite(n) 45–54

    Abstract: Objective: Fibroblast growth factor 21 (FGF21) has been shown to rapidly lower body weight in the Siberian hamster, a preclinical model of adiposity. This induced negative energy balance mediated by FGF21 is associated with both lowered caloric intake ... ...

    Abstract Objective: Fibroblast growth factor 21 (FGF21) has been shown to rapidly lower body weight in the Siberian hamster, a preclinical model of adiposity. This induced negative energy balance mediated by FGF21 is associated with both lowered caloric intake and increased energy expenditure. Previous research demonstrated that adipose tissue (AT) is one of the primary sites of FGF21 action and may be responsible for its ability to increase the whole-body metabolic rate. The present study sought to determine the relative importance of white (subcutaneous AT [sWAT] and visceral AT [vWAT]), and brown (interscapular brown AT [iBAT]) in governing FGF21-mediated metabolic improvements using the tissue-specific uptake of glucose and lipids as a proxy for metabolic activity.
    Methods: We used positron emission tomography-computed tomography (PET-CT) imaging in combination with both glucose (
    Results: Consistent with previous findings, FGF21 reduced body weight via reduced caloric intake and increased energy expenditure in the Siberian hamster. PET-CT studies demonstrated that FGF21 increased the uptake of glucose in BAT and WAT independently of reduced food intake and body weight as demonstrated by imaging of the pair-fed group. Furthermore, FGF21 increased glucose uptake in the primary adipocytes, confirming that these in vivo effects may be due to a direct action of FGF21 at the level of the adipocytes. Mechanistically, the effects of FGF21 are associated with activation of the ERK signaling pathway and upregulation of GLUT4 protein content in all fat depots. In response to treatment with FGF21, we observed an increase in the markers of lipolysis and lipogenesis in both the subcutaneous and visceral WAT depots. In contrast, FGF21 was only able to directly increase the uptake of lipid into BAT.
    Conclusions: These data identify brown and white fat depots as primary peripheral sites of action of FGF21 in promoting glucose uptake and also indicate that FGF21 selectively stimulates lipid uptake in brown fat, which may fuel thermogenesis.
    Mesh-Begriff(e) Adipose Tissue/diagnostic imaging ; Adipose Tissue/metabolism ; Animals ; Cricetinae ; Energy Metabolism ; Fibroblast Growth Factors/metabolism ; Male ; Phodopus ; Positron Emission Tomography Computed Tomography
    Chemische Substanzen fibroblast growth factor 21 ; Fibroblast Growth Factors (62031-54-3)
    Sprache Englisch
    Erscheinungsdatum 2019-11-09
    Erscheinungsland Germany
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2708735-9
    ISSN 2212-8778 ; 2212-8778
    ISSN (online) 2212-8778
    ISSN 2212-8778
    DOI 10.1016/j.molmet.2019.10.009
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Photoperiodic changes in adiposity increase sensitivity of female Siberian hamsters to systemic VGF derived peptide TLQP-21.

    Lisci, Carlo / Lewis, Jo E / Daniel, Zoe C T R / Stevenson, Tyler J / Monnier, Chloe / Marshall, Hayley J / Fowler, Maxine / Ebling, Francis J P / Ferri, Gian-Luca / Cocco, Cristina / Jethwa, Preeti H

    PloS one

    2019  Band 14, Heft 8, Seite(n) e0221517

    Abstract: TLQP-21, a peptide encoded by the highly conserved vgf gene, is expressed in neuroendocrine cells and has been the most prominent VGF-derived peptide studied in relation to control of energy balance. The recent discovery that TLQP-21 is the natural ... ...

    Abstract TLQP-21, a peptide encoded by the highly conserved vgf gene, is expressed in neuroendocrine cells and has been the most prominent VGF-derived peptide studied in relation to control of energy balance. The recent discovery that TLQP-21 is the natural agonist for the complement 3a receptor 1 (C3aR1) has revived interest in this peptide as a potential drug target for obesity. We have investigated its function in Siberian hamsters (Phodopus sungorus), a rodent that displays natural seasonal changes in body weight and adiposity as an adaptation to survive winter. We have previously shown that intracerebroventricular administration of TLQP-21 reduced food intake and body weight in hamsters in their long-day fat state. The aim of our current study was to determine the systemic actions of TLQP-21 on food intake, energy expenditure and body weight, and to establish whether adiposity affected these responses. Peripheral infusion of TLQP-21 (1mg/kg/day for 7 days) in lean hamsters exposed to short photoperiods (SP) reduced cumulative food intake in the home cage (p<0.05), and intake when measured in metabolic cages (P<0.01). Energy expenditure was significantly increased (p<0.001) by TLQP-21 infusion, this was associated with a significant increase in uncoupling protein 1 mRNA in brown adipose tissue (BAT) (p<0.05), and body weight was significantly reduced (p<0.05). These effects of systemic TLQP-21 treatment were not observed in hamsters exposed to long photoperiod (LP) with a fat phenotype. C3aR1 mRNA and protein were abundantly expressed in the hypothalamus, brown and white adipose tissue in hamsters, but changes in expression cannot explain the differential response to TLQP-21 in lean and fat hamsters.
    Mesh-Begriff(e) Adiposity/drug effects ; Animals ; Biomarkers ; Brain/metabolism ; Carbon Dioxide/metabolism ; Cricetinae ; Energy Metabolism ; Female ; Gene Expression ; Neuropeptides/pharmacology ; Oxygen/metabolism ; Peptide Fragments/pharmacology ; Photoperiod ; Receptors, Complement/metabolism
    Chemische Substanzen Biomarkers ; Neuropeptides ; Peptide Fragments ; Receptors, Complement ; TLQP-21 peptide ; VGF peptide ; Carbon Dioxide (142M471B3J) ; Oxygen (S88TT14065)
    Sprache Englisch
    Erscheinungsdatum 2019-08-29
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0221517
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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