Irisin alleviates hepatic steatosis by activating the autophagic SIRT3 pathway
Chinese Medical Journal,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 18, 2025
Abstract
Background:
Disruption
of
hepatic
lipid
homeostasis
leads
to
excessive
triglyceride
accumulation
and
the
development
metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD).
Autophagy,
a
critical
process
in
metabolism,
is
impaired
MASLD
pathogenesis.
Irisin,
skeletal
muscle-driven
myokine,
regulates
but
its
impact
on
metabolism
not
well
understood.
Here,
we
aimed
explore
role
irisin
steatosis
underlying
mechanisms
involved.
Methods:
A
high-fat
diet
(HFD)-induced
mouse
model
was
used,
recombinant
protein,
herein
referred
as
“Irisin”,
intraperitoneally
administered
for
4
weeks
evaluate
effects
accumulation.
Liver
tissues
were
stained
with
Oil
red
O
(ORO),
(TG)
total
cholesterol
(TC)
contents
measured
serum
homogenates.
The
expression
autophagosome
marker
microtubule-associated
protein
1
light
chain
3
(LC3),
autophagy
receptor
sequestosome-1
(SQSTM1/p62),
initiation
complex
unc-51-like
kinase
(ULK1)
lysosomal
functional
cathepsin
B
via
Western
blotting,
transcription
factor
EB
(TFEB)
analyzed
immunofluorescence
autophagic
changes.
effect
flux
further
evaluated
palmitic
acid-induced
HepG2
cells
by
measuring
degradation
chloroquine
(CQ),
analyzing
colocalization
LC3
lysosome-associated
(LAMP1).
possible
mechanism
examined
sirtuin
(SIRT3)
pathway
validated
using
overexpression
SIRT3
plasmid
transfection
or
siRNA-mediated
knockdown.
Student’s
t
-test
utilized
statistical
analysis.
Results:
Irisin
significantly
reduces
mice
fed
HFD,
accompanied
enhanced
hepatocyte
upregulation
pathway.
In
cells,
attenuated
accumulation,
which
partially
dependent
levels.
Mechanistically,
treatment
upregulated
phosphorylated
AMP-activated
(AMPK),
inhibited
mammalian
target
rapamycin
(mTOR)
activity,
promoted
TFEB
nucleus
translocation,
increased
expression,
degradation,
alleviated
steatosis.
No
significant
changes
phosphorylation
ULK1
hepatocytes
observed.
However,
when
siRNA
used
knock
down
,
those
reversed,
exacerbated.
Conclusions:
Our
findings
highlight
potential
therapeutic
modulating
potentially
providing
novel
management
MASLD.
Further
research
needed
elucidate
clinical
applications
this
approach
Язык: Английский
Mammalian nucleophagy: process and function
Autophagy,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 19, 2025
The
nucleus
is
a
highly
specialized
organelle
that
houses
the
cell's
genetic
material
and
regulates
key
cellular
activities,
including
growth,
metabolism,
protein
synthesis,
cell
division.
Its
structure
function
are
tightly
regulated
by
multiple
mechanisms
to
ensure
integrity
genomic
stability.
Increasing
evidence
suggests
nucleophagy,
selective
form
of
autophagy
targets
nuclear
components,
plays
critical
role
in
preserving
clearing
dysfunctional
materials
such
as
proteins
(lamins,
SIRT1,
histones),
DNA-protein
crosslinks,
micronuclei,
chromatin
fragments.
Impaired
nucleophagy
has
been
implicated
aging
various
pathological
conditions,
cancer,
neurodegeneration,
autoimmune
disorders,
neurological
injury.
In
this
review,
we
focus
on
mammalian
cells,
discussing
its
mechanisms,
regulation,
cargo
selection,
well
evaluating
therapeutic
potential
promoting
human
health
mitigating
disease.
Язык: Английский
Targeted proteomics addresses selectivity and complexity of protein degradation by autophagy
Autophagy,
Год журнала:
2024,
Номер
unknown, С. 1 - 16
Опубликована: Сен. 8, 2024
Macroautophagy/autophagy
is
a
constitutively
active
catabolic
lysosomal
degradation
pathway,
often
found
dysregulated
in
human
diseases.
It
considered
to
act
cytoprotective
manner
and
commonly
upregulated
cells
undergoing
stress.
Its
initiation
regulated
at
the
protein
level
does
not
require
Язык: Английский
Interactors and neighbors of ULK1 complex members
Autophagy,
Год журнала:
2024,
Номер
unknown, С. 1 - 3
Опубликована: Окт. 12, 2024
The
ULK1
kinase
complex
plays
a
crucial
role
in
autophagosome
biogenesis.
To
identify
interactors
or
regulators
of
assembly
influencing
biogenesis,
we
performed
an
interaction
proteomics
screen.
Employing
both
affinity
purification
and
proximity
labeling
N-
C-terminal
tagged
fusion
proteins
coupled
to
quantitative
mass
spectrometry,
identified
317
high-confidence
neighbors
the
four
members,
including
member-specific
common
interactors.
Interactions
with
selective
macroautophagy/autophagy
receptors
indicate
activation
autophagy
pathways
by
90
min
nutrient
starvation.
Focusing
on
effector
protein
BAG2,
interactor
approaches,
highlight
that
phosphorylates
supporting
localization
scaffold
inducer
AMBRA1
ER,
thereby
positively
regulating
initiation.
Язык: Английский