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  1. Article ; Online: AMPK and the Endocrine Control of Metabolism.

    Townsend, Logan K / Steinberg, Gregory R

    Endocrine reviews

    2023  Volume 44, Issue 5, Page(s) 910–933

    Abstract: Complex multicellular organisms require a coordinated response from multiple tissues to maintain whole-body homeostasis in the face of energetic stressors such as fasting, cold, and exercise. It is also essential that energy is stored efficiently with ... ...

    Abstract Complex multicellular organisms require a coordinated response from multiple tissues to maintain whole-body homeostasis in the face of energetic stressors such as fasting, cold, and exercise. It is also essential that energy is stored efficiently with feeding and the chronic nutrient surplus that occurs with obesity. Mammals have adapted several endocrine signals that regulate metabolism in response to changes in nutrient availability and energy demand. These include hormones altered by fasting and refeeding including insulin, glucagon, glucagon-like peptide-1, catecholamines, ghrelin, and fibroblast growth factor 21; adipokines such as leptin and adiponectin; cell stress-induced cytokines like tumor necrosis factor alpha and growth differentiating factor 15, and lastly exerkines such as interleukin-6 and irisin. Over the last 2 decades, it has become apparent that many of these endocrine factors control metabolism by regulating the activity of the AMPK (adenosine monophosphate-activated protein kinase). AMPK is a master regulator of nutrient homeostasis, phosphorylating over 100 distinct substrates that are critical for controlling autophagy, carbohydrate, fatty acid, cholesterol, and protein metabolism. In this review, we discuss how AMPK integrates endocrine signals to maintain energy balance in response to diverse homeostatic challenges. We also present some considerations with respect to experimental design which should enhance reproducibility and the fidelity of the conclusions.
    MeSH term(s) Animals ; Humans ; AMP-Activated Protein Kinases/metabolism ; Reproducibility of Results ; Energy Metabolism/physiology ; Homeostasis/physiology ; Insulin/metabolism ; Mammals/metabolism
    Chemical Substances AMP-Activated Protein Kinases (EC 2.7.11.31) ; Insulin
    Language English
    Publishing date 2023-06-02
    Publishing country United States
    Document type Review ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603096-8
    ISSN 1945-7189 ; 0163-769X
    ISSN (online) 1945-7189
    ISSN 0163-769X
    DOI 10.1210/endrev/bnad012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: New insights into activation and function of the AMPK.

    Steinberg, Gregory R / Hardie, D Grahame

    Nature reviews. Molecular cell biology

    2022  Volume 24, Issue 4, Page(s) 255–272

    Abstract: The classical role of AMP-activated protein kinase (AMPK) is as a cellular energy sensor activated by falling energy status, signalled by increases in AMP to ATP and ADP to ATP ratios. Once activated, AMPK acts to restore energy homeostasis by promoting ... ...

    Abstract The classical role of AMP-activated protein kinase (AMPK) is as a cellular energy sensor activated by falling energy status, signalled by increases in AMP to ATP and ADP to ATP ratios. Once activated, AMPK acts to restore energy homeostasis by promoting ATP-producing catabolic pathways while inhibiting energy-consuming processes. In this Review, we provide an update on this canonical (AMP/ADP-dependent) activation mechanism, but focus mainly on recently described non-canonical pathways, including those by which AMPK senses the availability of glucose, glycogen or fatty acids and by which it senses damage to lysosomes and nuclear DNA. We also discuss new findings on the regulation of carbohydrate and lipid metabolism, mitochondrial and lysosomal homeostasis, and DNA repair. Finally, we discuss the role of AMPK in cancer, obesity, diabetes, nonalcoholic steatohepatitis (NASH) and other disorders where therapeutic targeting may exert beneficial effects.
    MeSH term(s) AMP-Activated Protein Kinases/metabolism ; Energy Metabolism ; Lipid Metabolism ; Glucose/metabolism ; Adenosine Triphosphate/metabolism
    Chemical Substances AMP-Activated Protein Kinases (EC 2.7.11.31) ; Glucose (IY9XDZ35W2) ; Adenosine Triphosphate (8L70Q75FXE)
    Language English
    Publishing date 2022-10-31
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2031313-5
    ISSN 1471-0080 ; 1471-0072
    ISSN (online) 1471-0080
    ISSN 1471-0072
    DOI 10.1038/s41580-022-00547-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Environmental toxicants, brown adipose tissue, and potential links to obesity and metabolic disease.

    Wang, Bo / Steinberg, Gregory R

    Current opinion in pharmacology

    2022  Volume 67, Page(s) 102314

    Abstract: Rates of human obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) have risen faster than anticipated and cannot solely be explained by excessive caloric intake or physical inactivity. Importantly, this effect is also observed in many ...

    Abstract Rates of human obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) have risen faster than anticipated and cannot solely be explained by excessive caloric intake or physical inactivity. Importantly, this effect is also observed in many other domesticated and non-domesticated mammals, which has led to the hypothesis that synthetic environmental pollutants may be contributing to disease development. While the impact of these chemicals on appetite and adipogenesis has been extensively studied, their potential role in reducing energy expenditure is less studied. An important component of whole-body energy expenditure is adaptive and diet-induced thermogenesis in human brown adipose tissue (BAT). This review summarizes recent evidence that environmental pollutants such as the pesticide chlorpyrifos inhibit BAT function, diet-induced thermogenesis and the potential signaling pathways mediating these effects. Lastly, we discuss the importance of housing experimental mice at thermoneutrality, rather than room temperature, to maximize the translation of findings to humans.
    MeSH term(s) Humans ; Mice ; Animals ; Adipose Tissue, Brown/metabolism ; Diabetes Mellitus, Type 2/metabolism ; Thermogenesis ; Obesity/metabolism ; Energy Metabolism ; Environmental Pollutants/toxicity ; Environmental Pollutants/metabolism ; Mammals
    Chemical Substances Environmental Pollutants
    Language English
    Publishing date 2022-11-02
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2037057-X
    ISSN 1471-4973 ; 1471-4892
    ISSN (online) 1471-4973
    ISSN 1471-4892
    DOI 10.1016/j.coph.2022.102314
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Cellular Energy Sensing and Metabolism-Implications for Treating Diabetes: The 2017 Outstanding Scientific Achievement Award Lecture.

    Steinberg, Gregory R

    Diabetes

    2018  Volume 67, Issue 2, Page(s) 169–179

    Abstract: ... in the field of diabetes, taking into consideration independence of thought and originality. Gregory R ... Steinberg, PhD, professor of medicine, Canada Research Chair, J. Bruce Duncan Endowed Chair ...

    Abstract The Outstanding Scientific Achievement Award recognizes distinguished scientific achievement in the field of diabetes, taking into consideration independence of thought and originality. Gregory R. Steinberg, PhD, professor of medicine, Canada Research Chair, J. Bruce Duncan Endowed Chair in Metabolic Diseases, and codirector of the Metabolism and Childhood Obesity Research Program at McMaster University, Hamilton, Ontario, Canada, received the prestigious award at the American Diabetes Association's 77th Scientific Sessions, 9-13 June 2017, in San Diego, CA. He presented the Outstanding Scientific Achievement Award Lecture, "Cellular Energy Sensing and Metabolism-Implications for Treating Diabetes," on Monday, 12 June 2017.
    MeSH term(s) AMP-Activated Protein Kinases/metabolism ; Adipose Tissue, Beige/drug effects ; Adipose Tissue, Beige/metabolism ; Adipose Tissue, Beige/pathology ; Adipose Tissue, Brown/drug effects ; Adipose Tissue, Brown/metabolism ; Adipose Tissue, Brown/pathology ; Adipose Tissue, White/drug effects ; Adipose Tissue, White/metabolism ; Adipose Tissue, White/pathology ; Animals ; Awards and Prizes ; Caloric Restriction ; Cell Survival/drug effects ; Combined Modality Therapy ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; Diabetes Mellitus, Type 2/prevention & control ; Diabetes Mellitus, Type 2/therapy ; Endocrinology ; Energy Intake/drug effects ; Energy Metabolism/drug effects ; Enzyme Activation/drug effects ; Exercise ; Feedback, Physiological/drug effects ; Humans ; Hypoglycemic Agents/therapeutic use ; Insulin Resistance ; Liver/drug effects ; Liver/metabolism ; Liver/pathology ; Models, Biological ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/pathology ; Serotonin/blood ; Serotonin/metabolism ; Serotonin/secretion
    Chemical Substances Hypoglycemic Agents ; Serotonin (333DO1RDJY) ; AMP-Activated Protein Kinases (EC 2.7.11.31)
    Language English
    Publishing date 2018
    Publishing country United States
    Document type Journal Article ; Lectures ; Research Support, Non-U.S. Gov't
    ZDB-ID 80085-5
    ISSN 1939-327X ; 0012-1797
    ISSN (online) 1939-327X
    ISSN 0012-1797
    DOI 10.2337/dbi17-0039
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Current and emerging roles of adipose tissue in health and disease.

    Mottillo, Emilio P / Steinberg, Gregory R

    The Biochemical journal

    2020  Volume 477, Issue 19, Page(s) 3645–3647

    MeSH term(s) Adipocytes/metabolism ; Adipocytes/pathology ; Adipose Tissue/metabolism ; Adipose Tissue/pathology ; Animals ; Energy Metabolism ; Humans ; Obesity/metabolism ; Obesity/pathology
    Language English
    Publishing date 2020-11-03
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2969-5
    ISSN 1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
    ISSN (online) 1470-8728
    ISSN 0006-2936 ; 0306-3275 ; 0264-6021
    DOI 10.1042/BCJ20200718
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Lipogenesis inhibitors: therapeutic opportunities and challenges.

    Batchuluun, Battsetseg / Pinkosky, Stephen L / Steinberg, Gregory R

    Nature reviews. Drug discovery

    2022  Volume 21, Issue 4, Page(s) 283–305

    Abstract: Fatty acids are essential for survival, acting as bioenergetic substrates, structural components and signalling molecules. Given their vital role, cells have evolved mechanisms to generate fatty acids from alternative carbon sources, through a process ... ...

    Abstract Fatty acids are essential for survival, acting as bioenergetic substrates, structural components and signalling molecules. Given their vital role, cells have evolved mechanisms to generate fatty acids from alternative carbon sources, through a process known as de novo lipogenesis (DNL). Despite the importance of DNL, aberrant upregulation is associated with a wide variety of pathologies. Inhibiting core enzymes of DNL, including citrate/isocitrate carrier (CIC), ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), represents an attractive therapeutic strategy. Despite challenges related to efficacy, selectivity and safety, several new classes of synthetic DNL inhibitors have entered clinical-stage development and may become the foundation for a new class of therapeutics.
    MeSH term(s) ATP Citrate (pro-S)-Lyase/metabolism ; Acetyl-CoA Carboxylase/metabolism ; Fatty Acids ; Humans ; Lipogenesis ; Signal Transduction
    Chemical Substances Fatty Acids ; ATP Citrate (pro-S)-Lyase (EC 2.3.3.8) ; Acetyl-CoA Carboxylase (EC 6.4.1.2)
    Language English
    Publishing date 2022-01-14
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2062954-0
    ISSN 1474-1784 ; 1474-1776
    ISSN (online) 1474-1784
    ISSN 1474-1776
    DOI 10.1038/s41573-021-00367-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The mega-importance of de novo lipogenesis in platelet production.

    Nazy, Ishac / Arnold, Donald M / Steinberg, Gregory R

    Nature metabolism

    2020  Volume 2, Issue 10, Page(s) 999–1000

    Language English
    Publishing date 2020-09-14
    Publishing country Germany
    Document type Journal Article
    ISSN 2522-5812
    ISSN (online) 2522-5812
    DOI 10.1038/s42255-020-00282-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Preclinical evaluation of tolvaptan and salsalate combination therapy in a

    Song, Xuewen / Leonhard, Wouter N / Kanhai, Anish A / Steinberg, Gregory R / Pei, York / Peters, Dorien J M

    Frontiers in molecular biosciences

    2023  Volume 10, Page(s) 1058825

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2023-01-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2814330-9
    ISSN 2296-889X
    ISSN 2296-889X
    DOI 10.3389/fmolb.2023.1058825
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  9. Article ; Online: AMP-activated protein kinase: the current landscape for drug development.

    Steinberg, Gregory R / Carling, David

    Nature reviews. Drug discovery

    2019  Volume 18, Issue 7, Page(s) 527–551

    Abstract: Since the discovery of AMP-activated protein kinase (AMPK) as a central regulator of energy homeostasis, many exciting insights into its structure, regulation and physiological roles have been revealed. While exercise, caloric restriction, metformin and ... ...

    Abstract Since the discovery of AMP-activated protein kinase (AMPK) as a central regulator of energy homeostasis, many exciting insights into its structure, regulation and physiological roles have been revealed. While exercise, caloric restriction, metformin and many natural products increase AMPK activity and exert a multitude of health benefits, developing direct activators of AMPK to elicit beneficial effects has been challenging. However, in recent years, direct AMPK activators have been identified and tested in preclinical models, and a small number have entered clinical trials. Despite these advances, which disease(s) represent the best indications for therapeutic AMPK activation and the long-term safety of such approaches remain to be established.
    MeSH term(s) AMP-Activated Protein Kinases/chemistry ; AMP-Activated Protein Kinases/genetics ; AMP-Activated Protein Kinases/metabolism ; Animals ; Binding Sites ; Carbohydrate Metabolism/drug effects ; Drug Development/methods ; Energy Metabolism/drug effects ; Humans ; Lipid Metabolism/drug effects ; Protein Binding ; Protein Conformation ; Protein Isoforms ; Signal Transduction ; Small Molecule Libraries/chemistry ; Small Molecule Libraries/pharmacology ; Small Molecule Libraries/therapeutic use
    Chemical Substances Protein Isoforms ; Small Molecule Libraries ; AMP-Activated Protein Kinases (EC 2.7.11.31)
    Language English
    Publishing date 2019-03-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2062954-0
    ISSN 1474-1784 ; 1474-1776
    ISSN (online) 1474-1784
    ISSN 1474-1776
    DOI 10.1038/s41573-019-0019-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Author Correction: Metformin-induced ablation of microRNA 21-5p releases Sestrin-1 and CAB39L antitumoral activities.

    Pulito, Claudio / Mori, Federica / Sacconi, Andrea / Goeman, Frauke / Ferraiuolo, Maria / Pasanisi, Patrizia / Campagnoli, Carlo / Berrino, Franco / Fanciulli, Maurizio / Ford, Rebecca J / Levrero, Massimo / Pediconi, Natalia / Ciuffreda, Ludovica / Milella, Michele / Steinberg, Gregory R / Cioce, Mario / Muti, Paola / Strano, Sabrina / Blandino, Giovanni

    Cell discovery

    2024  Volume 10, Issue 1, Page(s) 29

    Language English
    Publishing date 2024-03-13
    Publishing country England
    Document type Published Erratum
    ISSN 2056-5968
    ISSN 2056-5968
    DOI 10.1038/s41421-024-00655-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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