We noted you are experiencing viewing problems
-
Check with your IT department that JWPlatform, JWPlayer and Amazon AWS & CloudFront are not being blocked by your network. The relevant domains are *.jwplatform.com, *.jwpsrv.com, *.jwpcdn.com, jwpltx.com, jwpsrv.a.ssl.fastly.net, *.amazonaws.com and *.cloudfront.net. The relevant ports are 80 and 443.
-
Check the following talk links to see which ones work correctly:
Auto Mode
HTTP Progressive Download Send us your results from the above test links at access@hstalks.com and we will contact you with further advice on troubleshooting your viewing problems. -
No luck yet? More tips for troubleshooting viewing issues
-
Contact HST Support access@hstalks.com
-
Please review our troubleshooting guide for tips and advice on resolving your viewing problems.
-
For additional help, please don't hesitate to contact HST support access@hstalks.com
We hope you have enjoyed this limited-length demo
This is a limited length demo talk; you may
login or
review methods of
obtaining more access.
- Fundamental aspects
-
1. Inflammation and tissue homeostasis
- Prof. Herman Waldmann
-
2. Introduction to the immune system
- Prof. Herman Waldmann
-
3. Hematopoiesis: the making of an immune system
- Prof. Paul J. Fairchild
-
4. Inflammation: purposes, mechanisms and development
- Prof. Pietro Ghezzi
-
5. Phagocytosis
- Dr. Eileen Uribe-Querol
-
6. Regulated cell death mechanisms and their crosstalk with the immune system 1
- Dr. Luis Alberto Baena-Lopez
-
7. Regulated cell death mechanisms and their crosstalk with the immune system 2
- Dr. Luis Alberto Baena-Lopez
- Innate immunity
-
11. Cells of the innate immune system
- Prof. Kevin Maloy
-
12. Microbial recognition and the immune response
- Dr. Dana Philpott
-
13. Toll-like receptor signalling during infection and inflammation
- Prof. Luke O'Neill
- Intercellular mediators
-
14. Chemokines
- Dr. James E. Pease
-
15. Cytokines
- Prof. Iain McInnes
-
16. IL-1 family cytokines as the canonical DAMPs of the immune system
- Prof. Seamus Martin
-
17. Glycans at the frontiers of inflammation, autoimmunity and cancer
- Prof. Salomé S. Pinho
-
18. Glycoimmunology
- Prof. Paula Videira
- Adaptive immunity B cells
-
21. Antigen recognition in the immune system
- Prof. Herman Waldmann
-
22. B cell biology
- Prof. Richard Cornall
-
23. Antibody structure and function: antibody structure
- Dr. Mike Clark
-
24. Antibody structure and function: antibody function
- Dr. Mike Clark
-
25. Antibody genes and diversity
- Dr. Mike Clark
-
26. In vivo antibody discovery and hybridoma technology
- Prof. Dr. Katja Hanack
-
27. Antibody engineering: beginnings to bispecifics and beyond
- Dr. Ian Wilkinson
-
29. The immunobiology of Fc receptors
- Prof. Mark Cragg
-
30. Immunoreceptors
- Prof. Anton van der Merwe
-
31. Affinity, avidity and kinetics in immune recognition
- Prof. Anton van der Merwe
- Adaptive immunity T cells
-
32. The thymus and T cell development: a primer
- Prof. Georg Holländer
-
33. Lineage decisions in the thymus: T cell lineage commitment
- Prof. Bruno Silva-Santos
-
34. Lineage decisions in the thymus: αβ and γδ T cell lineages
- Prof. Bruno Silva-Santos
-
35. CD4 T cell subsets
- Dr. Brigitta Stockinger
-
36. Cytotoxic T lymphocytes
- Prof. Gillian M. Griffiths
-
37. Gamma delta T-cells
- Prof. Bruno Silva-Santos
-
38. Tfh and Tfr cells
- Prof. Luis Graca
-
39. Tissue resident memory T cells (TRM)
- Dr. Marc Veldhoen
-
40. Mathematical modeling in immunology
- Prof. Ruy M. Ribeiro
- The importance of the MHC in immunity
-
41. The MHC and MHC molecules 1
- Prof. Jim Kaufman
-
42. The MHC and MHC molecules 2
- Prof. Jim Kaufman
-
43. Natural killer cells
- Dr. Philippa Kennedy
-
44. Human NK cells
- Prof. Lorenzo Moretta
-
46. NK cells in viral immunity
- Prof. Lewis Lanier
- Lymphocyte activation
-
47. Signal transduction by leukocyte receptors
- Dr. Omer Dushek
-
48. Immunological memory 1
- Prof. David Gray
-
49. Immunological memory 2
- Prof. David Gray
-
50. Studying immune responses “one cell at a time”
- Dr. Mir-Farzin Mashreghi
- Major cellular partners in immunity
-
51. The mononuclear phagocyte system - tissue resident macrophages: distribution and functions
- Prof. Emeritus Siamon Gordon
-
52. The mononuclear phagocyte system: tissue resident macrophages - activation and regulation
- Prof. Emeritus Siamon Gordon
-
53. Dendritic cells: professional antigen presenting cells
- Prof. Paul J. Fairchild
-
54. Mucosal immunology
- Prof. Daniel Mucida
- Immunological tolerance and regulation
-
55. Self-tolerance
- Prof. Herman Waldmann
-
56. Tolerance and autoimmunity
- Prof. Emerita Anne Cooke
-
57. The balance between intestinal immune homeostasis and inflammation
- Prof. Dr. Janneke Samsom
- Translational immunology - immune deficiency
-
58. Primary immunodeficiency disorders
- Dr. Smita Y. Patel
-
59. Changes in innate and adaptive immunity during human ageing 1
- Dr. Roel De Maeyer
-
60. Changes in innate and adaptive immunity during human ageing 2
- Dr. Roel De Maeyer
-
61. The aging immune system
- Prof. Ana Caetano
- Translational immunology - protection against pathogenic microbes
-
62. Immune responses to viruses
- Prof. Paul Klenerman
-
63. HIV and the immune system
- Prof. Quentin Sattentau
-
64. COVID-19: the anti-viral immune response
- Prof. Danny Altmann
-
65. Bacterial immune evasion
- Prof. Christoph Tang
-
66. The immunology underlying tuberculosis
- Prof. Thomas R. Hawn
-
67. Innate immunity to fungi
- Prof. Gordon D. Brown
-
68. Parasite immunity: introduction and Plasmodium
- Dr. Catarina Gadelha
-
69. Parasite immunity: Leishmania and Schistosoma
- Dr. Catarina Gadelha
-
70. Vaccination
- Dr. Anita Milicic
-
71. The history of vaccines 1
- Prof. Emeritus Anthony R. Rees
-
72. The history of vaccines 2
- Prof. Emeritus Anthony R. Rees
-
73. The history of vaccines 3
- Prof. Emeritus Anthony R. Rees
-
74. The science of vaccine adjuvants
- Dr. Derek O'Hagan
- Translational immunology - hypersensitivity, autoimmune disease and their management
-
75. Hypersensitivity diseases: type 1 hypersensitivity
- Prof. Herman Waldmann
-
76. Innate lymphoid cells in allergy
- Prof. Emeritus Shigeo Koyasu
-
77. Hypersensitivity diseases: type II-IV hypersensitivity
- Prof. Sara Marshall
-
78. Immune memory underlying lifelong peanut allergy
- Dr. Kelly Bruton
-
79. Memory B cells in allergy: B cell activation and response
- Dr. Kelly Bruton
-
80. Memory B cells in allergy: ontogeny, phenotype and plasticity
- Dr. Kelly Bruton
-
81. B cells at the crossroads of autoimmune diseases
- Dr. Xiang Lin
-
82. Interleukin-17: from clone to clinic
- Prof. Leonie Taams
-
83. Autoimmunity and type 1 diabetes
- Prof. Emerita Anne Cooke
-
84. What is new in type 1 diabetes?
- Prof. Åke Lernmark
-
85. Antibodies to control or prevent type 1 diabetes
- Dr. Robert Hilbrands
-
86. Monoclonal antibodies in haemato-oncology
- Prof. Mark Cragg
-
87. Therapeutic antibodies
- Dr. Geoffrey Hale
-
88. Endothelial cells: regulators of autoimmune-neuroinflammation
- Dr. Laure Garnier
-
89. Neuroimmunometabolism
- Prof. Ana Domingos
-
90. The immunology of multiple sclerosis
- Dr. Joanne Jones
-
91. Immunology of the peripheral nervous system: the inflammatory neuropathies
- Dr. Simon Rinaldi
-
92. Ocular immunology: an overview of immune mechanisms operating in the eye
- Dr. Eleftherios Agorogiannis
-
93. Understanding myasthenia gravis and advances in its management
- Prof. Henry J. Kaminski
-
94. The immunology underlying rheumatic diseases
- Dr. Hussein Al-Mossawi
-
96. Complement and lupus
- Prof. Marina Botto
-
97. Immune mechanisms in liver diseases
- Prof. Paul Klenerman
- Translational immunology - transplantation immunology
-
98. Principles of transplantation: overview of the immune response
- Prof. Emerita Kathryn Wood
-
99. Factors influencing outcomes in clinical transplantation 1
- Prof. Emerita Kathryn Wood
-
100. Factors influencing outcomes in clinical transplantation 2
- Prof. Emerita Kathryn Wood
- Translational immunology - cancer immunology
-
101. Cancer immunology
- Prof. Tim Elliott
-
102. Cancer immunotherapy
- Prof. Tim Elliott
-
103. Myeloid-derived suppressor cells in cancer
- Prof. Dmitry Gabrilovich
-
104. IL-2 in the immunotherapy of autoimmunity and cancer
- Prof. Thomas Malek
-
105. Latest advances in the development of CAR & TCR T-cell treatments for solid tumours
- Dr. Else Marit Inderberg
Printable Handouts
Navigable Slide Index
- Introduction
- What is neuroimmunometabolism?
- What we will cover today?
- Metabolism
- What regulates fat mass?
- Leptin action is not solely mediated by suppression of food intake
- How does leptin cause weight loss beyond suppression of food intake?
- The neuroendocrine loop of leptin action
- Tissue clearing techniques
- Sympathetic innervation of the iWAT
- Sympathetic neuro-adipose junctions
- Sympathetic neuro-adipose junctions: optogenetics
- Optogenetic stimulation drives NE release and lipolysis (1)
- Optogenetic stimulation drives NE release and lipolysis (2)
- Development of a drug for obesity
- Genetic sympathectomy mediates fast and irreversible obesity, independent of food intake
- Leptin-driven lipolysis
- The neuroendocrine loop of leptin beyond suppression food intake
- Leptin resistance in obesity
- The discovery of SAMs
- Sympathetic Associated Macrophages (SAMs)
- SAMs: RNAseq
- SAMs are more pro-inflammatory than ATMs
- SAMs express adrenergic genes
- SAM function?
- Studying SAMs in vitro
- SAMs do not have the machinery to synthesize NE
- SAMs can uptake and degrade NE
- SAMs import NE via NET (Slc6a2) to limit extracelluar NE
- SNS activation increases SAM inflammation
- Obesity increases SAMs
- Can obesity be reverted by LoF of SAMs?
- Looking for LoF tools or Cre drivers
- SAMs have Slc6a2, unlike other hematopoietic cells
- LoF of Slc6a2 leads to browning and thermogenesis
- LoF of Slc6a2 in SAMs leads to sustained weight loss independent of food intake
- Do SAMs exist in humans?
- Human SAMs
- Human SAMs: Slc6a2 and MAOa staining
- Macrophages can metabolise NE
- SAMs contribute to obesity by importing and metabolising NE
- Amphetamine
- Chemically modify AMPH to avoid the brain
- PEGyAMPH is brain-impermeable
- PEGyAMPH does not induce hyperkinesia and hypophagia
- PEGyAMPH facilitates SNS activity (1)
- PEGyAMPH facilitates SNS activity (2)
- PEGyAMPH defends against diet-induced obesity
- PEGyAMPH increases WAT NE and lipolysis
- PEGyAMPH reduces adipose mass
- PEGyAMPH increases energy expenditure (EE)
- PEGyAMPH increases thermogenesis
- PEGyAMPH increases thermal dissipation and prevents hyperthermia
- Thermogenesis coupled to heat dissipation
- PEGyAMPH doesn't increase HR or BP
- Cardiac side effects of AMPH are triggered by the brain
- Sympathofacilitators
- Sympathofacilitators bypass leptin resistence
- Acknowledgements
- Funding
Topics Covered
- What is neuroimmunometabolism
- Metabolism
- Regulation of adiposity by leptin
- Neuroendocrine loop of leptin action
- Stimulation of sympathetic neurons drives NE release and lipolysis
- Sympathetic neuron associated macrophages (SAMs)
- SAMs import and metabolise NE
- Anti-obesity drugs
- Sympathofacilitators bypass leptin resistance
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Domingos, A. (2023, October 31). Neuroimmunometabolism [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved February 5, 2025, from https://doi.org/10.69645/KWUM3436.Export Citation (RIS)
Publication History
Financial Disclosures
- No commercial/financial matters to disclose.
A selection of talks on Neuroscience
Transcript
Please wait while the transcript is being prepared...
0:00
Hello. My name is
Ana Domingos and I
am a professor of neuroscience
in the Department of Physiology,
Anatomy, and Genetics at
the University of Oxford.
The title of this talk is
Neuroimmunometabolism.
0:16
Neuroimmunometabolism
sounds a bit like
a German composite word in
which the words neuroscience,
immunology, and metabolism
are concatenated.
In this intro slide,
those three words are
conveniently color coded,
bringing to your attention,
sympathetic neurons in red which
are populated by immune cells in
green and both of which in turn
control the blue cells,
which are adipocytes.
Adipocytes are central to
the regulation of
metabolism and body weight.
0:46
What are we going
to cover today?
I will start with
the basic concept
in metabolism, for instance,
how leptin regulates body
weight and the primary evidence
supporting that leptin effect on
weight loss goes beyond
suppression of food intake.
I'll go over the discovery of
sympathetic neurons
in fat that are
the efferent arm in the
neuroendocrine loop of
leptin action by
decreasing fat mass.
I'll finally introduce the
concept of leptin resistance
and motivate the search for
biological mechanisms
outside of the brain.
Next, I'll delve into near
immunity by guiding you
through the experiments
that led to the discovery of
sympathetic neuron associated
macrophages that we often
call SAMs and how SAMs
contribute to obesity by
weakening the efferent arm in
the neuroendocrine
loop of leptin action.
Finally, I will talk about
potential anti-obesity
drugs that
capitalize on the
neuroimmunometabolic concepts
described in the
previous sections.
Namely, I'll talk
about the concept of
a sympathofacilitator
drug class that rescues
the weakened efferent arm in
the neuroendocrine loop
of the leptin action.