Immunometabolism,
Journal Year:
2025,
Volume and Issue:
7(2), P. e00059 - e00059
Published: March 19, 2025
In
the
last
couple
of
decades,
cancer
research
has
been
shifting
its
focus
to
immune
system.
Cancer
cells,
with
their
ability
adapt
and
evade
responses,
seem
accelerate
evolutionary
pressure
that
put
on
our
system
during
evolution.
We
thus
try
aid
these
natural
selection
processes
assist
combat
cancer.
Here,
we
are
discussing
a
study
by
Greg
Delgoffe
colleagues
was
published
in
Nature
Immunology
December
2024,
exploring
new
approach
bring
dysfunctional
cells
back
life
blocking
lactate
uptake.
Metabolites,
Journal Year:
2024,
Volume and Issue:
14(4), P. 194 - 194
Published: March 29, 2024
Inflammatory
bowel
disease
(IBD)
is
multifactorial
chronic
inflammatory
in
the
gastrointestinal
tract,
affecting
patients'
quality
of
life
profoundly.
The
incidence
IBD
has
been
on
rise
globally
for
last
two
decades.
Because
molecular
mechanisms
underlying
remain
not
well
understood,
therapeutic
development
significantly
impeded.
Metabolism
a
crucial
cellular
process
to
generate
energy
needed
an
response
and
tissue
repair.
Comprehensive
understanding
metabolic
pathways
would
help
unravel
pathogenesis/progression
facilitate
discoveries.
Here,
we
investigated
four
altered
experimental
colitis.
C57BL/6J
mice
were
treated
with
dextran
sulfate
sodium
(DSS)
drinking
water
7
days
induce
ulcerative
colitis
(UC).
We
conducted
proteomics
analysis
colon
samples
using
LC/MS,
profile
key
intermediates.
Our
findings
revealed
significant
alterations
major
pathways:
antioxidative
defense,
β-oxidation,
glycolysis,
TCA
cycle
pathways.
metabolism
by
downregulated
under
UC,
together
reduced
defense
These
results
reveal
re-programming
intestinal
cells
showing
dysregulation
all
study
underscores
importance
drivers
pathogenesis
suggests
that
modification
may
serve
as
novel
diagnostic/therapeutic
approach
IBD.
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: July 20, 2023
Inflammasomes
are
multiprotein
signaling
platforms
in
the
cytosol
that
senses
exogenous
and
endogenous
danger
signals
respond
with
maturation
secretion
of
IL-1β
IL-18
pyroptosis
to
induce
inflammation
protect
host.
The
inflammasome
best
studied
is
Nucleotide-binding
oligomerization
domain,
leucine-rich
repeat-containing
family
pyrin
domain
containing
3
(NLRP3)
inflammasome.
It
activated
a
two-step
process:
priming
activation,
leading
sensor
NLRP3
recruitment
both
adaptor
ASC
executioner
pro-caspase
1,
which
by
cleavage.
Moreover,
activation
regulated
posttranslational
modifications,
including
ubiquitination/deubiquitination,
phosphorylation/dephosphorylation,
acetylation/deacetylation,
SUMOylation
nitrosylation,
interaction
NLPR3
protein
binding
partners.
connection
between
it
metabolism
receiving
increasing
attention
this
field.
In
review,
we
present
structure,
functions,
regulation
NLRP3,
special
emphasis
on
mitochondrial
dysfunction-mtROS
production
metabolic
signals,
i.e.,
metabolites
as
well
enzymes.
By
understanding
specific
inhibitors
can
be
rationally
designed
for
treatment
prevention
various
immune-
or
metabolic-based
diseases.
Lastly,
review
current
their
mechanism
action.
Antioxidants,
Journal Year:
2024,
Volume and Issue:
13(4), P. 423 - 423
Published: March 29, 2024
Diabetic
retinopathy
(DR)
is
the
leading
cause
of
visual
impairment
and
blindness
among
working-age
population.
Microglia,
resident
immune
cells
in
retina,
are
recognized
as
crucial
drivers
DR
process.
Microglia
activation
a
tightly
regulated
immunometabolic
In
early
stages
DR,
M1
phenotype
commonly
shifts
from
oxidative
phosphorylation
to
aerobic
glycolysis
for
energy
production.
Emerging
evidence
suggests
that
microglia
not
only
engage
specific
metabolic
pathways
but
also
rearrange
their
oxidation-reduction
(redox)
system.
This
redox
adaptation
supports
reprogramming
offers
potential
therapeutic
strategies
using
antioxidants.
Here,
we
provide
an
overview
recent
insights
into
involvement
reactive
oxygen
species
distinct
roles
played
by
key
cellular
antioxidant
pathways,
including
NADPH
oxidase
2
system,
which
promotes
via
enhanced
glucose
transporter
4
translocation
cell
membrane
through
AKT/mTOR
pathway,
well
thioredoxin
nuclear
factor
E2-related
systems,
maintain
anti-inflammatory
state.
Therefore,
highlight
targeting
modulation
microglial
metabolism
offer
new
concepts
treatment.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(13), P. 6913 - 6913
Published: June 24, 2024
Chronic
exposure
to
harmful
pollutants,
chemicals,
and
pathogens
from
the
environment
can
lead
pathological
changes
in
epithelial
barrier,
which
increase
risk
of
developing
an
allergy.
During
allergic
inflammation,
cells
send
proinflammatory
signals
group
2
innate
lymphoid
cell
(ILC2s)
eosinophils,
require
energy
resources
mediate
their
activation,
cytokine/chemokine
secretion,
mobilization
other
cells.
This
review
aims
provide
overview
metabolic
regulation
asthma,
atopic
dermatitis
(AD),
rhinitis
(AR),
highlighting
its
underlying
mechanisms
phenotypes,
potential
regulatory
roles
eosinophils
ILC2s.
Eosinophils
ILC2s
regulate
inflammation
through
lipid
mediators,
particularly
cysteinyl
leukotrienes
(CysLTs)
prostaglandins
(PGs).
Arachidonic
acid
(AA)-derived
metabolites
Sphinosine-1-phosphate
(S1P)
are
significant
markers
that
indicate
immune
dysfunction
barrier
Notably,
promoters
symptoms
exhibit
greater
plasticity
compared
ILC2s,
directly
involved
promoting
symptoms.
Our
findings
suggest
metabolomic
analysis
provides
insights
into
complex
interactions
between
cells,
environmental
factors.
Potential
therapeutic
targets
have
been
highlighted
further
understand
Future
research
metabolomics
facilitate
development
novel
diagnostics
therapeutics
for
future
application.
How
bacterial
pathogens
exploit
host
metabolism
to
promote
immune
tolerance
and
persist
in
infected
hosts
remains
elusive.
To
achieve
this,
we
show
that
Pseudomonas
aeruginosa
(PA),
a
recalcitrant
pathogen,
utilizes
the
quorum
sensing
(QS)
signal
2-aminoacetophenone
(2-AA).
Here,
unveil
how
2-AA-driven
tolerization
causes
distinct
metabolic
perturbations
macrophages'
mitochondrial
respiration
bioenergetics.
We
present
evidence
indicating
these
effects
stem
from
decreased
pyruvate
transport
into
mitochondria.
This
reduction
is
attributed
expression
of
carrier
(MPC1),
which
mediated
by
diminished
nuclear
presence
its
transcriptional
regulator,
estrogen-related
receptor
alpha
(ERRα).
Consequently,
ERRα
exhibits
weakened
binding
MPC1
promoter.
outcome
arises
impaired
interaction
between
peroxisome
proliferator-activated
gamma
coactivator
1-alpha
(PGC-1α).
Ultimately,
this
cascade
results
influx
mitochondria
and,
consequently
reduced
ATP
production
tolerized
macrophages.
Exogenously
added
macrophages
restores
transcript
levels
ERR-α
enhances
cytokine
intracellular
clearance.
Consistent
with
vitro
findings,
murine
infection
studies
corroborate
2-AA-mediated
long-lasting
decrease
acetyl-CoA
association
PA
persistence,
further
supporting
QS
signaling
molecule
as
culprit
bioenergetic
alterations
persistence.
These
findings
2-AA
modulator
cellular
immunometabolism
reveal
an
unprecedented
mechanism
involving
PGC-1α/ERRα
axis
influence
on
MPC1/OXPHOS-dependent
energy
paradigmatic
pave
way
for
developing
treatments
bolster
resilience
pathogen-induced
damage.
Given
common
characteristic
prokaryotes,
it
likely
2-AA-like
molecules
similar
functions
may
be
other
pathogens.
Journal of Biological Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown, P. 108252 - 108252
Published: Feb. 1, 2025
Every
cell
in
the
body
is
exposed
to
a
certain
level
of
CO2
and
O2.
Hypercapnia
hypoxia
elicit
stress
signals
influence
cellular
metabolism
function.
Both
conditions
exert
profound
yet
distinct
effects
on
metabolic
pathways
mitochondrial
dynamics,
highlighting
need
for
cells
adapt
changes
gaseous
microenvironment.
The
interplay
between
hypercapnia
signalling
key
dictating
homeostasis
as
microenvironmental
O2
levels
are
inextricably
linked.
Hypercapnia,
characterized
by
elevated
pCO₂,
introduces
adaptations
within
aerobic
pathways,
affecting
TCA
cycle
flux,
lipid,
amino
acid
metabolism,
OXPHOS
ETC.
Hypoxia,
defined
reduced
oxygen
availability,
necessitates
shift
from
anaerobic
glycolysis
sustain
ATP
production,
process
orchestrated
stabilisation
HIF-1α.
Given
that
present
both
physiological
cancerous
microenvironments,
how
might
coexistence
function
niches
tumor
microenvironment?
