This slide show has been prepared to be presented in the 4th edition of World Congress on Endocrinology, Diabetes and Metabolism, (EDM 2023 Congress) Sep 07-08, 2023, Rome, Italy

1. ADAM17:
a sheddase involved at the crossroad of metabolism and immunity
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

2. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity
Reza Nejat, M. D., FCCM,
Anesthesiology and Critical Care Dept., Laleh Hospital,
Anti-Doping, Nutrition and Metabolism Consultant, World Powerlifting Ltd.,
Eurasia Division (Asia, Iran), Melbourne, Australia,
Former Assistant Professor, SBMU,

3. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity
Metabolism:
the whole sum of life-sustaining chemical
reactions:
occurring in cells and across whole organisms
endows the organism with the required energy
for:
 fulfilling vital processes
 synthesizing new organic material.
https://www.britannica.com/science/
metabolism
https://www.ncbi.nlm.nih.gov/books/
NBK546690/
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

4. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity Immunometabolism:
There are shared factors which both
affect metabolism and regulate
immune responses:
TNF-α, TGF-β, IL-1, IL-6, IL-8, IFNγ,
Matarese, G.; La Cava, A.
Trends in immunology 2004, 25 (4),
193.
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

5. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity
T cell development:
Requires activation PI3K-Akt-mTOR
pathway:
PI3K:
• dominates aerobic glycolysis
Akt:
• a major anabolism stimulus
mTOR:
♣ regulates glutaminolysis,
♣ glycolysis,
♣ mitochondrial biogenesis,
♣ protein synthesis
Zhang, M; et al.
Frontiers in Immunology 2022, 13,
946119
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

6. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity
Activation of Quiescent Leukocytes:
needs their energy expenditure to increase
increase by a factor of 1.30-1.50 (30-50
(30-50 percent)
Straub, R.; et al.
Journal of internal medicine 2010,
267 (6), 543.
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

7. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity Resting Metabolic Rate:
Should escalate up to 8-14% for
for activation of only mild forms of
forms of immune reaction.
Muehlenbein, M. P.; et al.
American Journal of Human Biology:
The Official Journal of the Human
Biology Association 2010, 22 (4), 546.
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

8. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity Metabolic reprogramming:
changes in cell metabolism
required for activation of immune
cells
M1 Mφ (killer):
• glycolytic metabolism
M2 Mφ (healer):
• TCA metabolism
Russell, D. G.; et al.
Nature Reviews Immunology 2019,
19 (5), 291.
Ley, K.
The Journal of Immunology 2017,
199 (7), 2191
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

9. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity
Transmembrane proteolysis:
a crucial contributor to in signal
transduction.
cleaves many of transmembrane
proteins to be released as soluble
molecules,
the soluble molecules initiate
cellular or intercellular signal
transduction
Wang, K.; et al.
Frontiers in Immunology 2022, 13,
1059376.
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

10. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity Mφ Metabolic Reprogramming:
Leads to activation of HIF-ADAM17
ADAM17 pathway
Lian, G.; et al.
EBioMedicine 2019, 49, 291
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

11. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity
Nejat, R.; Torshizi, M. F.; Najafi, D.
J. S Protein, ACE2 and Host Cell
Proteases in SARS-CoV-2 Cell Entry
and Infectivity; Is Soluble ACE2 a
Two Blade Sword? A Narrative
Review. Vaccines 2023, 11 (2), 204.
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

12. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity
Nejat, R.; Torshizi, M. F.; Najafi, D.
J. S Protein, ACE2 and Host Cell
Proteases in SARS-CoV-2 Cell Entry
and Infectivity; Is Soluble ACE2 a
Two Blade Sword? A Narrative
Review. Vaccines 2023, 11 (2), 204.
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

13. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity
ADAM17:
A member of ADAM family
Type I transmembrane protein
Exists in two forms:
Precursor
Activated
Critical for cleaving ectodomain of
many membrane proteins:
Cytokines (TNF-α, IL-6, IL-8, Il-10),
10),
ACE2,
Growth factors (EGF),
Receptors (TNF-R, IL-6R, EGF-R),
Pref-1
Adhesion molecules,
Wang, K.; et al.
Frontiers in Immunology 2022, 13,
1059376.
De Queiroz, T. M.; et al.
Frontiers in Pharmacology 2020, 11,
1154.
Matthews, J.; et al. Bioscience Reports
2021, 41 (5), BSR20210029
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

14. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity
ADAM17:
cleaving ectodomain of:
♣Cytokines (TNF-α, IL-6, IL-8, Il-10),
♣ACE2,
♣Growth factors (EGF),
♣Receptors (TNF-R, IL-6R, EGF-R),
♣Pref-1
♣Adhesion molecules,
Wang, K.; et al.
Frontiers in Immunology 2022, 13,
1059376.
De Queiroz, T. M.; et al.
Frontiers in Pharmacology 2020, 11,
1154.
Matthews, J.; et al. Bioscience Reports
2021, 41 (5), BSR20210029
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

15. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity Knockdown of ADAM17:
Downregulates EGFR-PI3K-Akt-
mTOR (survival) pathway
Leads to extremely lean
phenotype
Ameliorates cardiac dysfunction
in diabetic CMP
Zhang, Q.; et al.
Biochemical and biophysical research
communications 2018, 503 (4), 2333
Matthews, J; et al.
Bioscience Reports 2021, 41 (5),
BSR20210029.
Xue, F.; et al.
Signal Transduction and Targeted
Therapy 2022, 7 (1), 259.
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

16. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity ADAM17 shedding of EGFR
ligands:
Promotes tumor associated
macrophage M2 polarization
through EGFR-PI3K-Akt-mTOR
(survival) pathway
Wang, K.; et al. Frontiers in
Immunology 2022, 13, 1059376
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

17. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity ADAM17:
Mediates shedding of pro-
inflammatory TNF-α
Induces shedding of Insulin
Receptor ectodomain:
♣Promotes insulin resistance
♣Impairs insulin-mediated vasodilation
vasodilation
Ghiarone, T.; et al.
American Journal of Physiology-
Heart and Circulatory Physiology
2022, 323 (4), H688
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

18. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity
ADAM17:
• Cleaves SEMA4B
SEMA4B inhibits adipocytes:
♣Differentiation
♣Thermogenesis
♣Lipid catabolism
SEMA4B seems to mediate
recruitment of Tregs and
immunosuppressive cells
Amin, A.; et al. Molecular
Metabolism 2023, 73, 101731.
Jiang, J.; et al. BMC cancer 2022, 22
(1), 632.
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

19. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity ADAM17:
Upregulates in adipose tissue
endothelial cells through aging:
remote coronary microvascular
dysfunction
In white adipose tissue leads to:
expression of IL-6, MCP-1, SOCS3
low-grade inflammatory status
Dou, H.; et al.
Arteriosclerosis, thrombosis, and
vascular biology 2017, 37 (6), 1180
Menghini, R.; et al.
Atherosclerosis 2013, 228 (1), 12.
Serino, M.; et al.
Diabetes 2007, 56 (10), 2541
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

20. ADAM17:
a sheddase involved at the crossroad of
metabolism and immunity ADAM17:
• Modulates both metabolism and
immunity,
• Its downregulation and overexpression are
both hazardous,
• A special molecule as a promising target in:
• immunometabolic derangements,
• autoimmunity and cancer treatment
Conclusion
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant

21. ADAM17:
a sheddase involved at the
crossroad of metabolism
and immunity
by: Reza Nejat, M. D., FCCM; Anti-Doping, Nutrition, Metabolism Consultant