Brain Behavior and Immunity,
Journal Year:
2024,
Volume and Issue:
124, P. 280 - 293
Published: Dec. 11, 2024
Weight
loss
is
a
common
early
sign
in
amyotrophic
lateral
sclerosis
(ALS)
patients
and
negatively
correlates
with
survival.
In
different
cancers
metabolic
disorders,
high
levels
of
serum
growth
differentiation
factor
15
(GDF15)
contribute
to
decrease
food
intake
body
weight,
acting
through
GDNF
family
receptor
alpha-like
(GFRAL).
Here
we
report
that
GDF15
highly
expressed
the
peripheral
blood
ALS
hSOD1
Redox Biology,
Journal Year:
2025,
Volume and Issue:
unknown, P. 103613 - 103613
Published: March 1, 2025
Lifestyle
factors
such
as
a
Western
diet
or
metabolic
diseases
like
diabetes
disrupt
glucose
homeostasis
and
induce
stress
responses,
yet
their
impact
on
skin
metabolism
structural
integrity
remains
poorly
understood.
Here,
we
performed
multiomic
bioenergetic
analyses
of
human
dermal
fibroblasts
(HDFs),
equivalent
dermis
(HED),
reconstructed
(HRS),
explants
from
diabetic
patients.
We
found
that
12
mM
represses
oxidative
phosphorylation
(OXPHOS)
through
dual
mechanism:
the
glucose-dependent
nuclear
receptor
NR2F2
activates
mitochondrial
transcription
termination
factor
3
(MTERF3)
while
inhibiting
growth-differentiation
15
(GDF15).
Promoter
assays
revealed
MTERF3
is
regulated
by
MYCN,
whereas
GDF15
modulated
FOS.
Consequently,
OXPHOS
proteins
respiration
were
suppressed,
overexpression
additionally
interfered
with
collagen
biosynthesis.
In
contrast,
supplementation
fully
rescued
hyperglycemia-induced
metabolomic
alterations,
suggesting
pharmacological
strategy
to
mitigate
hyperglycemic
damage
in
skin.
Finally,
silencing
TFAM
impaired
fibroblast
haptotaxis
reconstruction,
underscoring
crucial
role
energetics
structure
function.
Collectively,
these
findings
identify
NR2F2-MTERF3-GDF15
axis
key
mediator
suppression
highlight
potential
therapeutic
target
preserve
under
stress.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(11), P. 5956 - 5956
Published: May 29, 2024
These
last
years,
the
growth
factor
GDF15
has
emerged
as
a
key
element
in
many
different
biological
processes.
It
been
established
being
produced
response
to
pathological
states
and
is
now
referred
stress-related
hormone.
Regarding
kidney
functions,
involved
pathologies
such
chronic
disease,
diabetic
nephropathy,
renal
cancer,
so
on.
Interestingly,
recent
studies
also
revealed
role
of
homeostatic
mechanisms
allowing
maintain
constant,
far
possible,
plasma
parameters
pH
K
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(13), P. 7313 - 7313
Published: July 3, 2024
Growth
differentiation
factor
15
(GDF-15)
is
a
multifunctional
cytokine
that
belongs
to
the
transforming
growth
factor-beta
(TGF-β)
superfamily.
GDF-15
involved
in
immune
tolerance
and
elevated
several
acute
chronic
stress
conditions,
often
correlating
with
disease
severity
patient
prognosis
cancer172
metabolic
cardiovascular
disorders.
Despite
these
clinical
associations,
molecular
mechanisms
orchestrating
its
effects
remain
be
elucidated.
The
of
are
pleiotropic
but
cell-specific
dependent
on
microenvironment.
While
expression
can
stimulated
by
inflammatory
mediators,
predominant
were
reported
as
anti-inflammatory
pro-fibrotic.
role
macrophage
system
has
been
increasingly
investigated
recent
years.
Macrophages
produce
high
levels
during
oxidative
lysosomal
stress,
which
lead
fibrogenesis
angiogenesis
at
tissue
level.
At
same
time,
macrophages
respond
switching
their
phenotype
tolerogenic
one.
Several
GDF-15-based
therapies
under
development,
including
analogs/mimetics
GDF-15-targeting
monoclonal
antibodies.
In
this
review,
we
summarize
major
physiological
pathological
contexts
interacts
macrophages.
We
also
discuss
challenges
future
perspectives
therapeutic
translation
GDF-15.
Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: Oct. 14, 2024
GDF15
and
FGF21,
stress-responsive
cytokines
primarily
secreted
from
the
liver,
are
promising
therapeutic
targets
for
metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD).
However,
interaction
between
FGF21
remains
unclear.
We
examined
effects
of
hepatocyte-specific
or
overexpression
in
high-fat
diet
(HFD)-fed
mice
8
weeks.
Hydrodynamic
injection
sustained
high
circulating
levels
respectively,
resulting
marked
reductions
body
weight,
epididymal
fat
mass,
insulin
resistance,
hepatic
steatosis.
In
addition,
treatment
led
to
early
reduction
weight
despite
no
change
food
intake,
indicating
role
other
than
appetite
loss.
increased
liver-derived
serum
levels,
whereas
did
not
affect
expression.
promoted
eIF2α
phosphorylation
XBP1
splicing,
leading
induction.
murine
AML12
hepatocytes
treated
with
free
fatty
acids
(FFAs),
upregulated
Fgf21
mRNA
splicing.
Overall,
continuous
exposure
excess
FFAs
resulted
a
gradual
increase
β-oxidation-derived
reactive
oxygen
species
endoplasmic
reticulum
stress,
suggesting
that
enhanced
this
pathway
induced
GDF15-
FGF21-related
crosstalk
is
an
important
MASLD.
BioScience Trends,
Journal Year:
2025,
Volume and Issue:
19(1), P. 72 - 86
Published: Jan. 24, 2025
Growth
and
differentiation
factor
15
(GDF15),
a
member
of
the
transforming
growth
factor-βsuperfamily,
is
considered
stress
response
has
garnered
increasing
attention
in
recent
years
due
to
its
roles
neurological
diseases.
Although
many
studies
have
suggested
that
GDF15
expression
elevated
patients
with
neurodegenerative
diseases
(NDDs),
glioma,
ischemic
stroke,
effects
increased
potential
underlying
mechanisms
remain
unclear.
Notably,
experimental
shown
multidimensional
beneficial
on
NDDs,
overexpression
able
rescue
NDD-associated
pathological
changes
phenotypes.
In
exerts
opposite
effects,
it
both
protumorigenic
antitumorigenic.
The
causes
these
conflicting
findings
are
not
comprehensively
clear,
but
inhibiting
helpful
for
suppressing
tumor
progression.
also
regarded
as
biomarker
poor
clinical
outcomes
stroke
patients,
targeting
may
help
prevent
this
disease.
Thus,
we
systematically
reviewed
synthesis,
transcriptional
regulation,
biological
functions
related
signaling
pathways
within
brain.
Furthermore,
explored
therapeutic
target
assessed
applicability
interventions
brain
By
integrating
latest
research
findings,
study
provides
new
insights
into
future
treatment
Nutrients,
Journal Year:
2024,
Volume and Issue:
16(8), P. 1106 - 1106
Published: April 10, 2024
Classical
examples
of
disorders
associated
with
body
image
disturbances
are
eating
(EDs)
such
as
anorexia
nervosa
(AN)
and
bulimia
(BN),
well
dysmorphic
disorder
(BDD)
[...]
