Change search
Refine search result
1 - 13 of 13
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. Cavalieri, Riccardo
    et al.
    Klein Hazebroek, Marlou
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Cotrim, Camila A.
    Lee, Yang
    Kunji, Edmund R. S.
    Jastroch, Martin
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Keipert, Susanne
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Crichton, Paul G.
    Activating ligands of Uncoupling protein 1 identified by rapid membrane protein thermostability shift analysis2022In: Molecular Metabolism, ISSN 2212-8778, Vol. 62, article id 101526Article in journal (Refereed)
    Abstract [en]

    Objective: Uncoupling protein 1 (UCP1) catalyses mitochondrial proton leak in brown adipose tissue to facilitate nutrient oxidation for heat production, and may combat metabolic disease if activated in humans. During the adrenergic stimulation of brown adipocytes, free fatty acids generated from lipolysis activate UCP1 via an unclear interaction. Here, we set out to characterise activator binding to purified UCP1 to clarify the activation process, discern novel activators and the potential to target UCP1.

    Methods: We assessed ligand binding to purified UCP1 by protein thermostability shift analysis, which unlike many conventional approaches can inform on the binding of hydrophobic ligands to membrane proteins. A detailed activator interaction analysis and screening approach was carried out, supported by investigations of UCP1 activity in liposomes, isolated brown fat mitochondria and UCP1 expression-controlled cell lines.

    Results: We reveal that fatty acids and other activators influence UCP1 through a specific destabilising interaction, behaving as transport substrates that shift the protein to a less stable conformation of a transport cycle. Through the detection of specific stability shifts in screens, we identify novel activators, including the over-the-counter drug ibuprofen, where ligand analysis indicates that UCP1 has a relatively wide structural specificity for interacting molecules. Ibuprofen successfully induced UCP1 activity in liposomes, isolated brown fat mitochondria and UCP1-expressing HEK293 cells but not in cultured brown adipocytes, suggesting drug delivery differs in each cell type.

    Conclusions: These findings clarify the nature of the activator-UCP1 interaction and demonstrate that the targeting of UCP1 in cells by approved drugs is in principle achievable as a therapeutic avenue, but requires variants with more effective delivery in brown adipocytes.

  • 2. Fischer, Katrin
    et al.
    Fenzl, Anna
    Liu, Dianxin
    Dyar, Kenneth A.
    Kleinert, Maximilian
    Brielmeier, Markus
    Clemmensen, Christoffer
    Fedl, Anna
    Finan, Brian
    Gessner, Andre
    Jastroch, Martin
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Helmholtz Diabetes Center (HDC), Germany; German National Diabetes Center (DZD), Germany.
    Huang, Jianfeng
    Keipert, Susanne
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Helmholtz Diabetes Center (HDC), Germany; German National Diabetes Center (DZD), Germany.
    Klingenspor, Martin
    Brüning, Jens C.
    Kneilling, Manfred
    Maier, Florian C.
    Othman, Ahmed E.
    Pichler, Bernd J.
    Pramme-Steinwachs, Ines
    Sachs, Stephan
    Scheideler, Angelika
    Thaiss, Wolfgang M.
    Uhlenhaut, Henriette
    Ussar, Siegfried
    Woods, Stephen C.
    Zorn, Julia
    Stemmer, Kerstin
    Collins, Sheila
    Diaz-Meco, Maria
    Moscat, Jorge
    Tschöp, Matthias H.
    Müller, Timo D.
    The scaffold protein p62 regulates adaptive thermogenesis through ATF2 nuclear target activation2020In: Nature Communications, E-ISSN 2041-1723, Vol. 11, no 1Article in journal (Refereed)
    Abstract [en]

    During beta -adrenergic stimulation of brown adipose tissue (BAT), p38 phosphorylates the activating transcription factor 2 (ATF2) which then translocates to the nucleus to activate the expression of Ucp1 and Pgc-1 alpha. The mechanisms underlying ATF2 target activation are unknown. Here we demonstrate that p62 (Sqstm1) binds to ATF2 to orchestrate activation of the Ucp1 enhancer and Pgc-1 alpha promoter. P62(Delta 69-251) mice show reduced expression of Ucp1 and Pgc-1 alpha with impaired ATF2 genomic binding. Modulation of Ucp1 and Pgc-1 alpha expression through p62 regulation of ATF2 signaling is demonstrated in vitro and in vivo in p62(Delta 69-251) mice, global p62(-/-) and Ucp1-Cre p62(flx/flx) mice. BAT dysfunction resulting from p62 deficiency is manifest after birth and obesity subsequently develops despite normal food intake, intestinal nutrient absorption and locomotor activity. In summary, our data identify p62 as a master regulator of BAT function in that it controls the Ucp1 pathway through regulation of ATF2 genomic binding. Beta-adrenergic stimulation of brown adipose tissue leads to thermogenesis via the activating transcription factor 2 (ATF2) mediated expression of the thermogenic genes Ucp1 and Pgc-1 alpha. Here, the authors show that the scaffold protein p62 regulates brown adipose tissue function through modifying ATF2 genomic binding and subsequent Ucp1 and Pgc-1 alpha induction.

  • 3. Grandoch, Maria
    et al.
    Floegel, Ulrich
    Virtue, Sam
    Maier, Julia K.
    Jelenik, Tomas
    Kohlmorgen, Christina
    Feldmann, Kathrin
    Ostendorf, Yanina
    Castaneda, Tamara R.
    Zhou, Zhou
    Yamaguchi, Yu
    Nascimento, Emmani B. M.
    Sunkari, Vivekananda G.
    Goy, Christine
    Kinzig, Martina
    Soergel, Fritz
    Bollyky, Paul L.
    Schrauwen, Patrick
    Al-Hasani, Hadi
    Roden, Michael
    Keipert, Susanne
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. German Center for Diabetes Research (DZD), Germany; Helmholtz Zentrum München, Germany.
    Vidal-Puig, Antonio
    Jastroch, Martin
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. German Center for Diabetes Research (DZD), Germany; Helmholtz Zentrum München, Germany.
    Haendeler, Judith
    Fischer, Jens W.
    4-Methylumbelliferone improves the thermogenic capacity of brown adipose tissue2019In: Nature Metabolism, E-ISSN 2522-5812, Vol. 1, no 5, p. 546-559Article in journal (Refereed)
    Abstract [en]

    Therapeutic increase in brown adipose tissue (BAT) thermogenesis is of great interest, as BAT activation counteracts obesity and insulin resistance. Hyaluronan (HA) is a glycosaminoglycan, found in the extracellular matrix, that is synthesized by HA synthases (HAS1, HAS2, and HAS3) from sugar precursors and accumulates in diabetic conditions. Its synthesis can be inhibited by the small molecule 4-methylumbelliferone (4-MU). Here we show that inhibition of HA synthesis by 4-MU or genetic deletion of Has2 and Has3 improves the thermogenic capacity of BAT, reduces body-weight gain, and improves glucose homeostasis independently of adrenergic stimulation in mice on a diabetogenic diet. In this context, we validated a novel magnetic resonce T2 mapping approach for in vivo visualization of BAT activation. Inhibition of HA synthesis increases glycolysis, BAT respiration, and uncoupling protein 1 (UCP1) expression. In addition, we show that 4-MU increases BAT capacity without inducing chronic stimulation and propose that 4-MU, a clinically approved, prescription-free drug, could be repurposed to treat obesity and diabetes.

  • 4. Karlina, Ruth
    et al.
    Lutter, Dominik
    Miok, Viktorian
    Fischer, David
    Altun, Irem
    Schöttl, Theresa
    Schorpp, Kenji
    Israel, Andreas
    Cero, Cheryl
    Johnson, James W.
    Kapser-Fischer, Ingrid
    Böttcher, Anika
    Keipert, Susanne
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Feuchtinger, Annette
    Graf, Elisabeth
    Strom, Tim
    Walch, Axel
    Lickert, Heiko
    Walzthoeni, Thomas
    Heinig, Matthias
    Theis, Fabian J.
    García-Cáceres, Cristina
    Cypess, Aaron M.
    Ussar, Siegfried
    Identification and characterization of distinct brown adipocyte subtypes in C57BL/6J mice2021In: Life Science Alliance, E-ISSN 2575-1077, Vol. 4, no 1, article id e202000924Article in journal (Refereed)
    Abstract [en]

    Brown adipose tissue (BAT) plays an important role in the regulation of body weight and glucose homeostasis. Although increasing evidence supports white adipose tissue heterogeneity, little is known about heterogeneity within murine BAT. Recently, UCP1 high and low expressing brown adipocytes were identified, but a developmental origin of these subtypes has not been studied. To obtain more insights into brown preadipocyte heterogeneity, we use single-cell RNA sequencing of the BAT stromal vascular fraction of C57/BL6 mice and characterize brown preadipocyte and adipocyte clonal cell lines. Statistical analysis of gene expression profiles from brown preadipocyte and adipocyte clones identify markers distinguishing brown adipocyte subtypes. We confirm the presence of distinct brown adipocyte populations in vivo using the markers EIF5, TCF25, and BIN1. We also demonstrate that loss of Bin1 enhances UCP1 expression and mitochondrial respiration, suggesting that BIN1 marks dormant brown adipocytes. The existence of multiple brown adipocyte subtypes suggests distinct functional properties of BAT depending on its cellular composition, with potentially distinct functions in thermogenesis and the regulation of whole body energy homeostasis.

  • 5.
    Keipert, Susanne
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Gaudry, Michael J.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Kutschke, Maria
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Keuper, Michaela
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Dela Rosa, Margeoux A. S.
    Cheng, Yiming
    Monroy Kuhn, José M.
    Laterveer, Rutger
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Cotrim, Camila A.
    Giere, Peter
    Perocchi, Fabiana
    Feederle, Regina
    Crichton, Paul G.
    Lutter, Dominik
    Jastroch, Martin
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Two-stage evolution of mammalian adipose tissue thermogenesis2024In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 384, no 6700, p. 1111-1117Article in journal (Refereed)
    Abstract [en]

    Brown adipose tissue (BAT) is a heater organ that expresses thermogenic uncoupling protein 1 (UCP1) to maintain high body temperatures during cold stress. BAT thermogenesis is considered an overarching mammalian trait, but its evolutionary origin is unknown. We show that adipose tissue of marsupials, which diverged from eutherian mammals ~150 million years ago, expresses a nonthermogenic UCP1 variant governed by a partial transcriptomic BAT signature similar to that found in eutherian beige adipose tissue. We found that the reconstructed UCP1 sequence of the common eutherian ancestor displayed typical thermogenic activity, whereas therian ancestor UCP1 is nonthermogenic. Thus, mammalian adipose tissue thermogenesis may have evolved in two distinct stages, with a prethermogenic stage in the common therian ancestor linking UCP1 expression to adipose tissue and thermal stress. We propose that in a second stage, UCP1 acquired its thermogenic function specifically in eutherians, such that the onset of mammalian BAT thermogenesis occurred only after the divergence from marsupials. 

  • 6.
    Keipert, Susanne
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. German Research Center for Environmental Health (GmbH), Germany; German Center for Diabetes Research (DZD), Germany.
    Lutter, Dominik
    Schroeder, Bjoern O.
    Brandt, Daniel
    Ståhlman, Marcus
    Schwarzmayr, Thomas
    Graf, Elisabeth
    Fuchs, Helmut
    de Angelis, Martin Hrabe
    Tschöp, Matthias H.
    Rozman, Jan
    Jastroch, Martin
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. German Research Center for Environmental Health (GmbH), Germany; German Center for Diabetes Research (DZD), Germany.
    Endogenous FGF21-signaling controls paradoxical obesity resistance of UCP1-deficient mice2020In: Nature Communications, E-ISSN 2041-1723, Vol. 11, no 1, article id 624Article in journal (Refereed)
    Abstract [en]

    Brown adipose thermogenesis increases energy expenditure and relies on uncoupling protein 1 (UCP1), however, UCP1 knock-out mice show resistance to diet-induced obesity at room temperature. Here, the authors show that this resistance relies on FGF21-signaling, inducing the browning of white adipose tissue. Uncoupling protein 1 (UCP1) executes thermogenesis in brown adipose tissue, which is a major focus of human obesity research. Although the UCP1-knockout (UCP1 KO) mouse represents the most frequently applied animal model to judge the anti-obesity effects of UCP1, the assessment is confounded by unknown anti-obesity factors causing paradoxical obesity resistance below thermoneutral temperatures. Here we identify the enigmatic factor as endogenous FGF21, which is primarily mediating obesity resistance. The generation of UCP1/FGF21 double-knockout mice (dKO) fully reverses obesity resistance. Within mild differences in energy metabolism, urine metabolomics uncover increased secretion of acyl-carnitines in UCP1 KOs, suggesting metabolic reprogramming. Strikingly, transcriptomics of metabolically important organs reveal enhanced lipid and oxidative metabolism in specifically white adipose tissue that is fully reversed in dKO mice. Collectively, this study characterizes the effects of endogenous FGF21 that acts as master regulator to protect from diet-induced obesity in the absence of UCP1.

  • 7.
    Keipert, Susanne
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Ost, Mario
    Stress-induced FGF21 and GDF15 in obesity and obesity resistance2021In: Trends in endocrinology and metabolism, ISSN 1043-2760, E-ISSN 1879-3061, Vol. 32, no 11, p. 904-915Article, review/survey (Refereed)
    Abstract [en]

    Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) are established as stress-responsive cytokines that can modulate energy balance by increasing energy expenditure or suppressing food intake, respectively. Despite their pharmacologically induced beneficial effects on obesity and comorbidities, circulating levels of both cytokines are elevated during obesity and related metabolic complications. On the other hand, endocrine crosstalk via FGF21 and GDF15 was also reported to play a crucial role in genetically modified mouse models of mitochondrial perturbations leading to diet-induced obesity (DIO) resistance. This review aims to dissect the complexities of endogenous FGF21 and GDF15 action in obesity versus DIO resistance for the regulation of energy balance in metabolic health and disease.

  • 8.
    Klein Hazebroek, Marlou
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Keipert, Susanne
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Adapting to the Cold: A Role for Endogenous Fibroblast Growth Factor 21 in Thermoregulation?2020In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 11, article id 389Article, review/survey (Refereed)
    Abstract [en]

    Fibroblast growth factor 21 (FGF21) is in biomedical focus as a treatment option for metabolic diseases, given that administration improves metabolism in mice and humans. The metabolic effects of exogenous FGF21 administration are well-characterized, but the physiological role of endogenous FGF21 has not been fully understood yet. Despite cold-induced FGF21 expression and increased circulating levels in some studies, which co-occur with brown fat thermogenesis, recent studies in cold-acclimated mice demonstrate the dispensability of FGF21 for maintenance of body temperature, thereby questioning FGF21's role for thermogenesis. Here we discuss the evidence either supporting or opposing the role of endogenous FGF21 for thermogenesis based on the current literature. FGF21, secreted by brown fat or liver, is likely not required for energy homeostasis in the cold, but the nutritional conditions could modulate the interaction between FGF21, energy metabolism, and thermoregulation.

  • 9.
    Klein Hazebroek, Marlou
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Keipert, Susanne
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Obesity-resistance of UCP1-deficient mice associates with sustained FGF21 sensitivity in inguinal adipose tissue2022In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 13, article id 909621Article in journal (Refereed)
    Abstract [en]

    Metabolic diseases represent the major health burden of our modern society. With the need of novel therapeutic approaches, fibroblast growth factor 21 (FGF21) is a promising target, based on metabolic improvements upon FGF21 administration in mice and humans. Endogenous FGF21 serum levels, however, are increased during obesity-related diseases, suggesting the development of FGF21 resistance during obesity and thereby lowering FGF21 efficacy. In uncoupling protein 1 knockout (UCP1 KO) mice, however, elevated endogenous FGF21 levels mediate resistance against diet-induced obesity. Here, we show that after long-term high fat diet feeding (HFD), circulating FGF21 levels become similarly high in obese wildtype and obesity-resistant UCP1 KO mice, suggesting improved FGF21 sensitivity in UCP1 KO mice. To test this hypothesis, we injected FGF21 after long-term HFD and assessed the metabolic and molecular effects. The UCP1 KO mice lost weight directly upon FGF21 administration, whereas body weights of WT mice resisted weight loss in the initial phase of the treatment. The FGF21 treatment induced expression of liver Pck1, a typical FGF21-responsive gene, in both genotypes. In iWAT, FGF21-responsive genes were selectively induced in UCP1 KO mice, strongly associating FGF21-sensitivity in iWAT with healthy body weights. Thus, these data support the concept that FGF21-sensitivity in adipose tissue is key for metabolic improvements during obesogenic diets.

  • 10.
    Klein Hazebroek, Marlou
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Laterveer, Rutger
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden.
    Kutschke, Maria
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Ramsak Marceta, Vida
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Barthem, Clarissa S.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Keipert, Susanne
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Hyperphagia of female UCP1-deficient mice blunts anti-obesity effects of FGF212023In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1, article id 10288Article in journal (Refereed)
    Abstract [en]

    Increasing energy expenditure through uncoupling protein 1 (UCP1) activity in thermogenic adipose tissue is widely investigated to correct diet-induced obesity (DIO). Paradoxically, UCP1-deficient male mice are resistant to DIO at room temperature. Recently, we uncovered a key role for fibroblast growth factor 21 (FGF21), a promising drug target for treatment of metabolic disease, in this phenomenon. As the metabolic action of FGF21 is so far understudied in females, we aim to investigate potential sexual dimorphisms. Here, we confirm that male UCP1 KO mice display resistance to DIO in mild cold, without significant changes in metabolic parameters. Surprisingly, females gained the same amount of body fat as WT controls. Molecular regulation was similar between UCP1 KO males and females, with an upregulation of serum FGF21, coinciding with beiging of inguinal white adipose tissue and induced lipid metabolism. While energy expenditure did not display significant differences, UCP1 KO females significantly increased their food intake. Altogether, our results indicate that hyperphagia is likely counteracting the beneficial effects of FGF21 in female mice. This underlines the importance of sex-specific studies in (pre)clinical research for personalized drug development.

  • 11. Ost, Mario
    et al.
    Igual Gil, Carla
    Coleman, Verena
    Keipert, Susanne
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Efstathiou, Sotirios
    Vidic, Veronika
    Weyers, Miriam
    Klaus, Susanne
    Muscle-derived GDF15 drives diurnal anorexia and systemic metabolic remodeling during mitochondrial stress2020In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 21, no 3, article id e48804Article in journal (Refereed)
    Abstract [en]

    Mitochondrial dysfunction promotes metabolic stress responses in a cell-autonomous as well as organismal manner. The wasting hormone growth differentiation factor 15 (GDF15) is recognized as a biomarker of mitochondrial disorders, but its pathophysiological function remains elusive. To test the hypothesis that GDF15 is fundamental to the metabolic stress response during mitochondrial dysfunction, we investigated transgenic mice (Ucp1-TG) with compromised muscle-specific mitochondrial OXPHOS capacity via respiratory uncoupling. Ucp1-TG mice show a skeletal muscle-specific induction and diurnal variation of GDF15 as a myokine. Remarkably, genetic loss of GDF15 in Ucp1-TG mice does not affect muscle wasting or transcriptional cell-autonomous stress response but promotes a progressive increase in body fat mass. Furthermore, muscle mitochondrial stress-induced systemic metabolic flexibility, insulin sensitivity, and white adipose tissue browning are fully abolished in the absence of GDF15. Mechanistically, we uncovered a GDF15-dependent daytime-restricted anorexia, whereas GDF15 is unable to suppress food intake at night. Altogether, our evidence suggests a novel diurnal action and key pathophysiological role of mitochondrial stress-induced GDF15 in the regulation of systemic energy metabolism.

  • 12. Zhang, Qian
    et al.
    Delessa, Challa Tenagne
    Augustin, Robert
    Bakhti, Mostafa
    Colldén, Gustav
    Drucker, Daniel J.
    Feuchtinger, Annette
    Garcia Caceres, Cristina
    Grandl, Gerald
    Harger, Alexandra
    Herzig, Stephan
    Hofmann, Susanna
    Holleman, Cassie Lynn
    Jastroch, Martin
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Keipert, Susanne
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Kleinert, Maximilian
    Knerr, Patrick J.
    Kulaj, Konxhe
    Legutko, Beata
    Lickert, Heiko
    Liu, Xue
    Luippold, Gerd
    Lutter, Dominik
    Malogajski, Emilija
    Tarquis Medina, Marta
    Mowery, Stephanie A.
    Blutke, Andreas
    Perez-Tilve, Diego
    Salinno, Ciro
    Sehrer, Laura
    DiMarchi, Richard D.
    Tschöp, Matthias H.
    Stemmer, Kerstin
    Finan, Brian
    Wolfrum, Christian
    Müller, Timo D.
    The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling2021In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 33, no 4, p. 833-844Article in journal (Refereed)
    Abstract [en]

    Uncertainty exists as to whether the glucose-dependent insulinotropic polypeptide receptor (GIPR) should be activated or inhibited for the treatment of obesity. Gipr was recently demonstrated in hypothalamic feeding centers, but the physiological relevance of CNS Gipr remains unknown. Here we show that HFD-fed CNS-Gipr KO mice and humanized (h)GIPR knockin mice with CNS-hGIPR deletion show decreased body weight and improved glucose metabolism. In DIO mice, acute central and peripheral administration of acyl-GIP increases cFos neuronal activity in hypothalamic feeding centers, and this coincides with decreased body weight and food intake and improved glucose handling. Chronic central and peripheral administration of acyl-GIP lowers body weight and food intake in wild-type mice, but shows blunted/absent efficacy in CNS-Gipr KO mice. Also, the superior metabolic effect of GLP-1/GIP co-agonism relative to GLP-1 is extinguished in CNS-Gipr KO mice. Our data hence establish a key role of CNS Gipr for control of energy metabolism.

  • 13. Ziqubu, Khanyisani
    et al.
    Dludla, Phiwayinkosi V.
    Mabhida, Sihle E.
    Jack, Babalwa U.
    Keipert, Susanne
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Jastroch, Martin
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Mazibuko-Mbeje, Sithandiwe E.
    Brown adipose tissue-derived metabolites and their role in regulating metabolism2024In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 150, article id 155709Article, review/survey (Refereed)
    Abstract [en]

    The discovery and rejuvenation of metabolically active brown adipose tissue (BAT) in adult humans have offered a new approach to treat obesity and metabolic diseases. Beyond its accomplished role in adaptive thermogenesis, BAT secretes signaling molecules known as “batokines”, which are instrumental in regulating whole-body metabolism via autocrine, paracrine, and endocrine action. In addition to the intrinsic BAT metabolite-oxidizing activity, the endocrine functions of these molecules may help to explain the association between BAT activity and a healthy systemic metabolic profile. Herein, we review the evidence that underscores the significance of BAT-derived metabolites, especially highlighting their role in controlling physiological and metabolic processes involving thermogenesis, substrate metabolism, and other essential biological processes. The conversation extends to their capacity to enhance energy expenditure and mitigate features of obesity and its related metabolic complications. Thus, metabolites derived from BAT may provide new avenues for the discovery of metabolic health-promoting drugs with far-reaching impacts. This review aims to dissect the complexities of the secretory role of BAT in modulating local and systemic metabolism in metabolic health and disease.

1 - 13 of 13
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf