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  1. Article ; Online: Role of lipids in the metabolism and activation of immune cells.

    Hubler, Merla J / Kennedy, Arion J

    The Journal of nutritional biochemistry

    2015  Volume 34, Page(s) 1–7

    Abstract: Immune cell plasticity has extensive implications in the pathogenesis and resolution of metabolic disorders, cancers, autoimmune diseases and chronic inflammatory disorders. Over the past decade, nutritional status has been discovered to influence the ... ...

    Abstract Immune cell plasticity has extensive implications in the pathogenesis and resolution of metabolic disorders, cancers, autoimmune diseases and chronic inflammatory disorders. Over the past decade, nutritional status has been discovered to influence the immune response. In metabolic disorders such as obesity, immune cells interact with various classes of lipids, which are capable of controlling the plasticity of macrophages and T lymphocytes. The purpose of this review is to discuss lipids and their impact on innate and adaptive immune responses, focusing on two areas: (1) the impact of altering lipid metabolism on immune cell activation, differentiation and function and (2) the mechanism by which lipids such as cholesterol and fatty acids regulate immune cell plasticity.
    MeSH term(s) Adaptive Immunity ; Cardiovascular Diseases/etiology ; Cardiovascular Diseases/immunology ; Cardiovascular Diseases/metabolism ; Cardiovascular Diseases/pathology ; Cell Plasticity ; Dietary Fats/adverse effects ; Dietary Fats/metabolism ; Humans ; Immunity, Cellular ; Immunity, Innate ; Lipid Metabolism ; Macrophages/cytology ; Macrophages/immunology ; Macrophages/metabolism ; Macrophages/pathology ; Models, Immunological ; Non-alcoholic Fatty Liver Disease/etiology ; Non-alcoholic Fatty Liver Disease/immunology ; Non-alcoholic Fatty Liver Disease/metabolism ; Non-alcoholic Fatty Liver Disease/pathology ; Nutritional Status ; Obesity/etiology ; Obesity/immunology ; Obesity/metabolism ; Obesity/pathology ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; T-Lymphocytes/pathology
    Chemical Substances Dietary Fats
    Language English
    Publishing date 2015-11-24
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1014929-6
    ISSN 1873-4847 ; 0955-2863
    ISSN (online) 1873-4847
    ISSN 0955-2863
    DOI 10.1016/j.jnutbio.2015.11.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: MFe

    Hubler, Merla J / Erikson, Keith M / Kennedy, Arion J / Hasty, Alyssa H

    American journal of physiology. Cell physiology

    2018  Volume 315, Issue 3, Page(s) C319–C329

    Abstract: Resident adipose tissue macrophages (ATMs) play multiple roles to maintain tissue homeostasis, such as removing excess free fatty acids and regulation of the extracellular matrix. The phagocytic nature and oxidative resiliency of macrophages not only ... ...

    Abstract Resident adipose tissue macrophages (ATMs) play multiple roles to maintain tissue homeostasis, such as removing excess free fatty acids and regulation of the extracellular matrix. The phagocytic nature and oxidative resiliency of macrophages not only allows them to function as innate immune cells but also to respond to specific tissue needs, such as iron homeostasis. MFe
    MeSH term(s) Adipocytes/metabolism ; Adipocytes/physiology ; Adipose Tissue/metabolism ; Adipose Tissue/physiology ; Animals ; Cell Line ; Dietary Supplements ; Inflammation/metabolism ; Inflammation/physiopathology ; Iron Overload/metabolism ; Iron Overload/physiopathology ; Iron, Dietary/metabolism ; Macrophages/metabolism ; Macrophages/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Monocytes/metabolism ; Monocytes/physiology
    Chemical Substances Iron, Dietary
    Language English
    Publishing date 2018-05-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 392098-7
    ISSN 1522-1563 ; 0363-6143
    ISSN (online) 1522-1563
    ISSN 0363-6143
    DOI 10.1152/ajpcell.00103.2018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Role of lipids in the metabolism and activation of immune cells

    Hubler, Merla J / Arion J. Kennedy

    Journal of nutritional biochemistry. 2016 Aug., v. 34

    2016  

    Abstract: Immune cell plasticity has extensive implications in the pathogenesis and resolution of metabolic disorders, cancers, autoimmune diseases and chronic inflammatory disorders. Over the past decade, nutritional status has been discovered to influence the ... ...

    Abstract Immune cell plasticity has extensive implications in the pathogenesis and resolution of metabolic disorders, cancers, autoimmune diseases and chronic inflammatory disorders. Over the past decade, nutritional status has been discovered to influence the immune response. In metabolic disorders such as obesity, immune cells interact with various classes of lipids, which are capable of controlling the plasticity of macrophages and T lymphocytes. The purpose of this review is to discuss lipids and their impact on innate and adaptive immune responses, focusing on two areas: (1) the impact of altering lipid metabolism on immune cell activation, differentiation and function and (2) the mechanism by which lipids such as cholesterol and fatty acids regulate immune cell plasticity.
    Keywords adaptive immunity ; autoimmune diseases ; cholesterol ; chronic diseases ; fatty acids ; immune response ; lipid metabolism ; macrophages ; metabolic diseases ; neoplasms ; nutritional status ; obesity ; pathogenesis ; T-lymphocytes
    Language English
    Dates of publication 2016-08
    Size p. 1-7.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 1014929-6
    ISSN 1873-4847 ; 0955-2863
    ISSN (online) 1873-4847
    ISSN 0955-2863
    DOI 10.1016/j.jnutbio.2015.11.002
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Iron homeostasis: a new job for macrophages in adipose tissue?

    Hubler, Merla J / Peterson, Kristin R / Hasty, Alyssa H

    Trends in endocrinology and metabolism: TEM

    2015  Volume 26, Issue 2, Page(s) 101–109

    Abstract: Elevated serum ferritin and increased cellular iron concentrations are risk factors for diabetes; however, the etiology of this association is unclear. Metabolic tissues such as pancreas, liver, and adipose tissue (AT), as well as the immune cells ... ...

    Abstract Elevated serum ferritin and increased cellular iron concentrations are risk factors for diabetes; however, the etiology of this association is unclear. Metabolic tissues such as pancreas, liver, and adipose tissue (AT), as well as the immune cells resident in these tissues, may be involved. Recent studies demonstrate that the polarization status of macrophages has important relevance to their iron-handling capabilities. Furthermore, a subset of macrophages in AT have elevated iron concentrations and a gene expression profile indicative of iron handling, a capacity diminished in obesity. Because iron overload in adipocytes increases systemic insulin resistance, iron handling by AT macrophages may have relevance not only to adipocyte iron stores but also to local and systemic insulin sensitivity.
    MeSH term(s) Adipocytes/metabolism ; Adipose Tissue/metabolism ; Animals ; Homeostasis/physiology ; Humans ; Iron/metabolism ; Iron Overload/epidemiology ; Iron Overload/metabolism ; Macrophages/physiology ; Metabolic Syndrome/epidemiology ; Metabolic Syndrome/metabolism ; Obesity/epidemiology ; Obesity/metabolism
    Chemical Substances Iron (E1UOL152H7)
    Language English
    Publishing date 2015-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 1042384-9
    ISSN 1879-3061 ; 1043-2760
    ISSN (online) 1879-3061
    ISSN 1043-2760
    DOI 10.1016/j.tem.2014.12.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Mathematical estimation of recovery after loss of activity: I. Renal failure.

    Hübler, Merla J / Buchman, Timothy G

    The Journal of trauma

    2007  Volume 63, Issue 1, Page(s) 232–238

    MeSH term(s) Acute Kidney Injury/diagnosis ; Acute Kidney Injury/physiopathology ; Acute Kidney Injury/therapy ; Adult ; Body Water ; Creatinine/blood ; Female ; Glomerular Filtration Rate/physiology ; Humans ; Kidney/physiopathology ; Male ; Mathematics ; Models, Biological ; Recovery of Function/physiology ; Renal Dialysis ; Time Factors
    Chemical Substances Creatinine (AYI8EX34EU)
    Language English
    Publishing date 2007-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 219302-4
    ISSN 1529-8809 ; 0022-5282 ; 1079-6061
    ISSN (online) 1529-8809
    ISSN 0022-5282 ; 1079-6061
    DOI 10.1097/TA.0b013e318068ddae
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Calcitriol and Levothyroxine Dosing for Patients With Pseudohypoparathyroidism.

    Antoun, Jacqueline / Williamson, Dylan / Hubler, Merla / Shoemaker, Ashley H

    Journal of the Endocrine Society

    2021  Volume 5, Issue 12, Page(s) bvab161

    Abstract: Pseudohypoparathyroidism (PHP) is a rare hormone resistance syndrome caused by mutations ... ...

    Abstract Pseudohypoparathyroidism (PHP) is a rare hormone resistance syndrome caused by mutations in
    Language English
    Publishing date 2021-10-27
    Publishing country United States
    Document type Journal Article
    ISSN 2472-1972
    ISSN (online) 2472-1972
    DOI 10.1210/jendso/bvab161
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Mathematical estimates of recovery after loss of activity: II. Long-range connectivity facilitates rapid functional recovery.

    Hübler, Merla J / Buchman, Timothy G

    Critical care medicine

    2008  Volume 36, Issue 2, Page(s) 489–494

    Abstract: Objective: To model the effects of system connectedness on recovery of dysfunctional tissues.: Design: One-dimensional elementary cellular automata models with small-world features, where the center-input for a few cells comes not from itself but, ... ...

    Abstract Objective: To model the effects of system connectedness on recovery of dysfunctional tissues.
    Design: One-dimensional elementary cellular automata models with small-world features, where the center-input for a few cells comes not from itself but, with a given probability, from another cell. This probability represents the connectivity of the network. The long-range connections are chosen randomly to survey the potential influences of distant information flowing into a local region.
    Setting: MATLAB and Mathematica computing environments.
    Patients: None.
    Interventions: None.
    Measurements and main results: We determined the recovery rate of the entropy after perturbing a uniformly dormant system. We observed that the recovery of normal activity after perturbation of a dormant system had the characteristics of an epidemic. Moreover, we found that the rate of recovery to normal steady-state activity increased rapidly even for small amounts of long-range connectivity. Findings obtained through numerical simulation were verified through analytical solutions.
    Conclusions: This study links our hypothesis that multiple organ function syndromes represent recoupling failure with a mathematical model showing the contribution of such coupling to reactivation of dormant systems. The implication is that strategies aimed not at target tissues or target organs but rather at restoring the quality and quantity of interconnections across those tissues and organs may be a novel therapeutic strategy.
    MeSH term(s) Algorithms ; Humans ; Models, Biological ; Multiple Organ Failure/etiology ; Multiple Organ Failure/physiopathology ; Multiple Organ Failure/prevention & control ; Neural Networks (Computer) ; Recovery of Function/physiology ; Signal Transduction/physiology ; Systems Theory ; Time Factors
    Language English
    Publishing date 2008-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 197890-1
    ISSN 1530-0293 ; 0090-3493
    ISSN (online) 1530-0293
    ISSN 0090-3493
    DOI 10.1097/CCM.0B013E318162942C
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Elevating adipose eosinophils in obese mice to physiologically normal levels does not rescue metabolic impairments

    W. Reid Bolus / Kristin R. Peterson / Merla J. Hubler / Arion J. Kennedy / Marnie L. Gruen / Alyssa H. Hasty

    Molecular Metabolism, Vol 8, Iss , Pp 86-

    2018  Volume 95

    Abstract: Objective: Obesity is a metabolic disorder that has reached epidemic proportions worldwide and leads to increased risk for diabetes, cardiovascular disease, asthma, certain cancers, and various other diseases. Obesity and its comorbidities are associated ...

    Abstract Objective: Obesity is a metabolic disorder that has reached epidemic proportions worldwide and leads to increased risk for diabetes, cardiovascular disease, asthma, certain cancers, and various other diseases. Obesity and its comorbidities are associated with impaired adipose tissue (AT) function. In the last decade, eosinophils have been identified as regulators of proper AT function. Our study aimed to determine whether normalizing the number of AT eosinophils in obese mice, to those of lean healthy mice, would reduce obesity and/or improve metabolic fitness. Methods: C57BL/6J mice fed a high fat diet (HFD) were simultaneously given recombinant interleukin-5 (rIL5) for 8 weeks to increase AT eosinophils. Metabolic fitness was tested by evaluating weight gain, AT inflammation, glucose, lipid, and mixed-meal tolerance, AT insulin signaling, energy substrate utilization, energy expenditure, and white AT beiging capacity. Results: Eosinophils were increased ∼3-fold in AT of obese HFD-fed mice treated with rIL5, and thus were restored to levels observed in lean healthy mice. However, there were no significant differences in rIL5-treated mice among the above listed comprehensive set of metabolic assays, despite the increased AT eosinophils. Conclusions: We have shown that restoring obese AT eosinophils to lean healthy levels is not sufficient to allow for improvement in any of a range of metabolic features otherwise impaired in obesity. Thus, the mechanisms that identified eosinophils as positive regulators of AT function, and therefore systemic health, are more complex than initially understood and will require further study to fully elucidate. : Restoring obese adipose eosinophils to lean adipose levels via rIL5 administration is not sufficient to regain metabolic fitness Author Video: Author Video Watch what authors say about their articles Keywords: Inflammation, Obesity, Diabetes, Eosinophils, Interleukin 5, Adipose tissue
    Keywords Internal medicine ; RC31-1245
    Subject code 570
    Language English
    Publishing date 2018-02-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Elevating adipose eosinophils in obese mice to physiologically normal levels does not rescue metabolic impairments.

    Bolus, W Reid / Peterson, Kristin R / Hubler, Merla J / Kennedy, Arion J / Gruen, Marnie L / Hasty, Alyssa H

    Molecular metabolism

    2017  Volume 8, Page(s) 86–95

    Abstract: Objective: Obesity is a metabolic disorder that has reached epidemic proportions worldwide and leads to increased risk for diabetes, cardiovascular disease, asthma, certain cancers, and various other diseases. Obesity and its comorbidities are ... ...

    Abstract Objective: Obesity is a metabolic disorder that has reached epidemic proportions worldwide and leads to increased risk for diabetes, cardiovascular disease, asthma, certain cancers, and various other diseases. Obesity and its comorbidities are associated with impaired adipose tissue (AT) function. In the last decade, eosinophils have been identified as regulators of proper AT function. Our study aimed to determine whether normalizing the number of AT eosinophils in obese mice, to those of lean healthy mice, would reduce obesity and/or improve metabolic fitness.
    Methods: C57BL/6J mice fed a high fat diet (HFD) were simultaneously given recombinant interleukin-5 (rIL5) for 8 weeks to increase AT eosinophils. Metabolic fitness was tested by evaluating weight gain, AT inflammation, glucose, lipid, and mixed-meal tolerance, AT insulin signaling, energy substrate utilization, energy expenditure, and white AT beiging capacity.
    Results: Eosinophils were increased ∼3-fold in AT of obese HFD-fed mice treated with rIL5, and thus were restored to levels observed in lean healthy mice. However, there were no significant differences in rIL5-treated mice among the above listed comprehensive set of metabolic assays, despite the increased AT eosinophils.
    Conclusions: We have shown that restoring obese AT eosinophils to lean healthy levels is not sufficient to allow for improvement in any of a range of metabolic features otherwise impaired in obesity. Thus, the mechanisms that identified eosinophils as positive regulators of AT function, and therefore systemic health, are more complex than initially understood and will require further study to fully elucidate.
    MeSH term(s) Adipose Tissue/drug effects ; Adipose Tissue/pathology ; Animals ; Energy Metabolism ; Eosinophils/drug effects ; Insulin/metabolism ; Interleukin-5/pharmacology ; Interleukin-5/therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/drug therapy ; Obesity/pathology
    Chemical Substances Insulin ; Interleukin-5
    Language English
    Publishing date 2017-12-16
    Publishing country Germany
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 2212-8778
    ISSN (online) 2212-8778
    DOI 10.1016/j.molmet.2017.12.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Review and experimental evaluation of the embryonic development and evolutionary history of flipper development and hyperphalangy in dolphins (Cetacea: Mammalia).

    Cooper, Lisa Noelle / Sears, Karen E / Armfield, Brooke A / Kala, Bhavneet / Hubler, Merla / Thewissen, J G M

    Genesis (New York, N.Y. : 2000)

    2017  Volume 56, Issue 1

    Abstract: Cetaceans are the only mammals to have evolved hyperphalangy, an increase in the number of phalanges beyond the mammalian plesiomorphic condition of three phalanges per digit. In this study, cetaceans were used as a novel model to review previous studies ...

    Abstract Cetaceans are the only mammals to have evolved hyperphalangy, an increase in the number of phalanges beyond the mammalian plesiomorphic condition of three phalanges per digit. In this study, cetaceans were used as a novel model to review previous studies of mammalian hyperphalangy and contribute new experimental evidence as to the molecular origins of this phenotype in embryos of the pantropical spotted dolphin (Stenella attenuata). Results show embryos of dolphins, mice, and pigs share similar spatiotemporal patterns of signaling proteins known to shape limbs of mammals (e.g., FGF8, BMP2/4, WNT, GREM). However, fetal dolphins differ in that their interdigital tissues are retained, instead of undergoing apoptosis, and that multiple waves of interdigital signals likely contribute to the patterning of supernumerary joints and phalanges in adjacent digits. Integration of fossil and experimental evidence suggests that the presence of interdigital webbing within the fossils of semi-aquatic cetaceans, recovered from the Eocene Epoch (49Ma), was probably the result of BMP-antagonists counteracting interdigital apoptosis during embryonic limb development. Modifications to signals originating in these interdigital tissues likely contributed to the origin of an incipient form of hyperphalangy in obligatorily aquatic cetaceans about 35Ma. Finally, an extreme form of hyperphalangy, with six or more phalanges per digit, evolved independently in rorqual whales (Balaenopteridae) and delphinids, and was probably associated with a wave of signaling within the interdigital tissues.
    MeSH term(s) Animals ; Biological Evolution ; Body Patterning ; Dolphins/embryology ; Extremities/embryology ; Mammals
    Language English
    Publishing date 2017-10-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2004544-X
    ISSN 1526-968X ; 1526-954X
    ISSN (online) 1526-968X
    ISSN 1526-954X
    DOI 10.1002/dvg.23076
    Database MEDical Literature Analysis and Retrieval System OnLINE

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