Metabolites,
Год журнала:
2024,
Номер
14(1), С. 40 - 40
Опубликована: Янв. 8, 2024
This
narrative
review
aims
to
illustrate
the
notion
that
nonalcoholic
steatohepatitis
(NASH),
recently
renamed
metabolic
dysfunction-associated
(MASH),
is
a
systemic
disorder
featuring
both
adverse
hepatic
and
extrahepatic
outcomes.
In
recent
years,
several
NASH
trials
have
failed
identify
effective
pharmacological
treatments
and,
therefore,
lifestyle
changes
are
cornerstone
of
therapy
for
NASH.
with
this
context,
we
analyze
epidemiological
burden
possible
pathogenetic
factors
involved.
These
include
genetic
factors,
insulin
resistance,
lipotoxicity,
immuno-thrombosis,
oxidative
stress,
reprogramming
metabolism,
hypoxia,
all
which
eventually
culminate
in
low-grade
chronic
inflammation
increased
risk
fibrosis
progression.
The
explanations
underlying
failure
also
accurately
examined.
We
conclude
high
heterogeneity
NASH,
resulting
from
variable
backgrounds,
exposure,
responses
different
stresses,
susceptibility
hepatocyte
differences
repair-response,
calls
personalized
medicine
approaches
involving
research
on
noninvasive
biomarkers.
Future
should
aim
at
achieving
complete
assessment
determinants,
modifiers,
correlates
thus
adopting
more
holistic
unbiased
approach,
notably
including
cardiovascular–kidney–metabolic
outcomes,
without
restricting
therapeutic
perspectives
histological
surrogates
liver-related
outcomes
alone.
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
14
Опубликована: Янв. 19, 2024
In
light
of
a
global
rise
in
the
number
patients
with
type
2
diabetes
mellitus
(T2DM)
and
obesity,
non-alcoholic
fatty
liver
disease
(NAFLD),
now
known
as
metabolic
dysfunction-associated
(MAFLD)
or
steatotic
(MASLD),
has
become
leading
cause
hepatocellular
carcinoma
(HCC),
annual
occurrence
MASLD-driven
HCC
expected
to
increase
by
45%–130%
2030.
Although
MASLD
serious
major
public
health
threat
globally,
exact
molecular
mechanisms
mediating
remain
an
open
problem,
necessitating
future
investigation.
Meanwhile,
emerging
studies
are
focusing
on
utility
bioactive
compounds
halt
progression
HCC.
this
review,
we
first
briefly
review
recent
progress
possible
pathogenesis
for
We
then
discuss
application
mitigate
through
different
modulatory
encompassing
anti-inflammatory,
lipid
metabolic,
gut
microbial
pathways,
providing
valuable
information
treatment
prevention
Nonetheless,
clinical
research
exploring
effectiveness
herbal
medicines
is
still
warranted.
Annals of Hepatology,
Год журнала:
2025,
Номер
unknown, С. 101777 - 101777
Опубликована: Янв. 1, 2025
Non-alcoholic
fatty
liver
disease
(NAFLD),
now
recognized
as
metabolic
dysfunction-associated
steatotic
(MASLD),
represents
a
significant
and
escalating
global
health
challenge.
Its
prevalence
is
intricately
linked
to
obesity,
insulin
resistance,
other
components
of
the
syndrome.
As
our
comprehension
MASLD
deepens,
it
has
become
evident
that
this
condition
extends
beyond
liver,
embodying
complex,
multi-systemic
with
hepatic
manifestations
mirror
broader
landscape.
This
comprehensive
review
delves
into
critical
interplay
between
gut-liver
axis
oxidative
stress,
elucidating
their
pivotal
roles
in
etiology
progression
MASLD.
Our
analysis
reveals
several
key
findings:
(1)
Bile
acid
dysregulation
can
trigger
stress
through
enhanced
ROS
production
hepatocytes
Kupffer
cells,
leading
mitochondrial
dysfunction
lipid
peroxidation;
(2)
Gut
microbiota
dysbiosis
disrupts
intestinal
barrier
function,
allowing
increased
translocation
endotoxins
like
LPS,
which
activate
inflammatory
pathways
TLR4
signaling
promote
via
NADPH
oxidase
activation;
(3)
The
redox-sensitive
transcription
factors
NF-κB
Nrf2
serve
crucial
mediators
axis,
regulating
responses
orchestrating
antioxidant
defenses;
(4)
Oxidative
stress-induced
damage
function
creates
destructive
feedback
loop,
further
exacerbating
inflammation
progression.
These
findings
highlight
complex
interrelationship
pathogenesis,
suggesting
potential
therapeutic
targets
for
management.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids,
Год журнала:
2024,
Номер
1869(7), С. 159515 - 159515
Опубликована: Июнь 5, 2024
Although
our
current
knowledge
of
the
molecular
crosstalk
between
ER
stress,
unfolded
protein
response
(UPR),
and
lipid
homeostasis
remains
limited,
there
is
increasing
evidence
that
dysregulation
either
or
profoundly
affects
other.
Most
research
regarding
UPR
signaling
in
human
diseases
has
focused
on
causes
consequences
disrupted
folding.
The
itself
consists
very
complex
pathways
function
to
not
only
maintain
homeostasis,
but
just
as
importantly,
modulate
biogenesis
allow
adjust
promote
cell
survival.
Lipid
known
activate
many
aspects
UPR,
complexity
this
a
major
barrier.
disequilibrium
lipotoxicity
are
be
important
contributors
numerous
pathologies,
including
insulin
resistance,
liver
disease,
cardiovascular
diseases,
neurodegenerative
cancer.
Despite
their
medical
significance
continuous
research,
however,
mechanisms
synthesis
during
stress
conditions,
impact
fate
decisions,
remain
poorly
understood.
Here
we
summarize
view
connections
altered
metabolism,
UPR.
Maternal
obesity
and
over/undernutrition
can
have
a
long-lasting
impact
on
offspring
health
during
critical
periods
in
the
first
1000
days
of
life.
Children
born
to
mothers
with
reduced
immune
responses
stimuli
which
increase
susceptibility
infections.
Recently,
maternal
western-style
diets
(WSD),
high
fat
simple
sugars,
been
associated
skewing
neonatal
cell
development,
recent
evidence
suggests
that
dysregulation
innate
immunity
early
life
has
long-term
consequences
metabolic
diseases
behavioral
disorders
later
Several
factors
contribute
abnormal
tolerance
or
trained
immunity,
including
changes
gut
microbiota,
metabolites,
epigenetic
modifications.
Critical
knowledge
gaps
remain
regarding
mechanisms
whereby
these
fetal
postnatal
especially
precursor
stem
cells
bone
marrow
liver.
Components
microbiota
are
transferred
from
consuming
WSD
their
understudied
identifying
cause
effect
adaptive
development
needs
be
refined.
Tools
single-cell
RNA-sequencing,
analysis,
spatial
location
specific
liver
for
understanding
system
programming.
Considering
vital
role
function
plays
health,
it
will
important
understand
how
control
developmental
programming
immunity.
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Фев. 6, 2024
The
global
prevalence
of
type
2
diabetes
mellitus
(T2DM)
and
Alzheimer’s
disease
(AD)
is
rapidly
increasing,
revealing
a
strong
association
between
these
two
diseases.
Currently,
there
are
no
curative
medication
available
for
the
comorbidity
T2DM
AD.
Ceramides
structural
components
cell
membrane
lipids
act
as
signal
molecules
regulating
homeostasis.
Their
synthesis
degradation
play
crucial
roles
in
maintaining
metabolic
balance
vivo
,
serving
important
mediators
development
neurodegenerative
disorders.
Abnormal
ceramide
metabolism
disrupts
intracellular
signaling,
induces
oxidative
stress,
activates
inflammatory
factors,
impacts
glucose
lipid
homeostasis
metabolism-related
tissues
like
liver,
skeletal
muscle,
adipose
tissue,
driving
occurrence
progression
T2DM.
connection
changes
levels
brain,
amyloid
β
accumulation,
tau
hyper-phosphorylation
evident.
Additionally,
regulates
survival
apoptosis
through
related
signaling
pathways,
actively
participating
Regulatory
enzymes,
their
metabolites,
pathways
impact
core
pathological
molecular
mechanisms
shared
by
AD,
such
insulin
resistance
response.
Consequently,
may
become
potential
therapeutic
target
intervention
paper
comprehensively
summarizes
discusses
role
its
metabolites
pathogenesis
well
latest
progress
treatment
with
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
174, С. 116585 - 116585
Опубликована: Апрель 13, 2024
Emerging
research
into
metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD)
up
until
January
2024
has
highlighted
the
critical
role
of
cuproptosis,
a
unique
cell
death
mechanism
triggered
by
copper
overload,
in
disease's
development.
This
connection
offers
new
insights
MASLD's
complex
pathogenesis,
pointing
to
accumulation
as
key
factor
that
disrupts
lipid
metabolism
and
insulin
sensitivity.
The
identification
cuproptosis
significant
contributor
MASLD
underscores
potential
for
targeting
copper-mediated
pathways
novel
therapeutic
approaches.
promising
avenue
suggests
managing
levels
could
mitigate
progression,
offering
fresh
perspective
on
treatment
strategies.
Further
investigations
how
influences
are
essential
unraveling
detailed
mechanisms
at
play
identifying
effective
interventions.
focus
copper's
health
opens
possibility
developing
targeted
therapies
address
underlying
causes
MASLD,
moving
beyond
symptomatic
tackle
root
problem.
exploration
context
exemplifies
importance
understanding
metal
homeostasis
diseases
represents
step
forward
quest
more
treatments.
direction
lights
path
innovative
management
reversal.
This
open
question
research
article
highlights
mitochondria-associated
endoplasmic
reticulum
(ER)
membranes
(MAMs),
which
have
emerged
as
crucial
cellular
structures
that
challenge
our
traditional
understanding
of
organelle
function.
review
the
critical
importance
MAMs
a
frontier
in
cell
biology
with
far-reaching
implications
for
health,
disease
and
ageing.
serve
dynamic
communication
hubs
between
ER
mitochondria,
orchestrating
essential
processes
such
calcium
signalling,
lipid
metabolism
stress
responses.
Recent
has
implicated
MAM
dysfunction
wide
array
conditions,
including
neurodegenerative
diseases,
metabolic
disorders,
cardiovascular
diseases
cancer.
The
significant
lack
biological
knowledge
behind
function
emphasizes
need
to
study
these
enigmatic
subcellular
sites
greater
detail.
Key
questions
include
mechanisms
controlling
formation
disassembly,
full
complement
MAM-associated
proteins
how
contribute
decision-making
ageing
processes.
Advancing
through
interdisciplinary
approaches
cutting-edge
technologies
promises
reveal
new
insights
into
fundamental
signalling
pathways
potentially
lead
innovative
therapeutic
strategies
range
diseases.
As
such,
represents
potential
transform
life
human
health.
