British Journal of Pharmacology,
Год журнала:
2024,
Номер
181(16), С. 2774 - 2793
Опубликована: Апрель 21, 2024
Abstract
Background
and
Purpose
White
adipose
tissue
(WAT)
is
involved
in
rheumatoid
arthritis
(RA).
This
study
explored
its
potential
as
an
antirheumatic
target.
Experimental
Approach
WAT
status
of
healthy
adjuvant‐induced
(AIA)
rats
were
compared.
The
contribution
to
RA
pathology
was
evaluated
by
pre‐adipocyte
transplant
experiments
dissecting
perirenal
fat
pads
AIA
rats.
impact
on
investigated
culturing
pre‐adipocytes.
Proteins
differentially
expressed
identified
the
UPLC/MS
2
method.
These
together
with
PPARγ
siRNA
agonist
used
treat
pre‐adipocytes
vitro.
medium
for
THP‐1
monocyte
culture.
Key
Results
Compared
controls,
smaller
but
secreted
more
leptin,
eNAMPT,
MCP‐1,
TNF‐α,
IL‐6.
rat
increased
levels
these
adipokines
recipients.
patients'
serum
induced
a
similar
secretion
change
impaired
differentiation
Adipectomy
eased
AIA‐related
immune
abnormalities
arthritic
manifestations.
Hepatokines
PON1,
IGFBP4,
GPIHBP1
among
differential
proteins
high
blood,
inflammatory
secretions
inhibited
expression
caused
impairment
pre‐adipocytes,
outcome
PPARγ‐silencing.
endowed
cells
ability
activate
monocytes,
which
can
be
abrogated
rosiglitazone.
Conclusion
Implications
Certain
hepatokines
potentiate
expedite
progression
inhibiting
PPARγ.
Targeting
this
signalling
or
abnormal
various
approaches
may
reduce
severity.
Journal of Hepatology,
Год журнала:
2023,
Номер
79(6), С. 1524 - 1541
Опубликована: Сен. 18, 2023
While
the
links
between
metabolic
dysfunction
associated
steatotic
liver
disease
(MASLD)
and
obesity,
insulin
resistance
are
widely
appreciated,
there
a
host
of
complex
interactions
other
endocrine
axes.
it
can
be
difficult
to
definitively
distinguish
direct
causal
relationships
those
attributable
increased
adipocyte
mass,
is
substantial
evidence
indirect
specific
dysregulation
severity
MASLD.
Strong
effects
exists
for
low
levels
growth
hormone,
sex
hormones,
thyroid
hormone
with
development
disease.
The
impact
steroid
e.g.
cortisol
dehydropepiandrosterone,
adipokines
much
more
divergent.
Thoughtful
assessment,
based
on
individual
risk
factors
findings,
also
management
non-insulin
axes
should
performed
in
evaluation
Multiple
therapeutic
pharmaceutical
targets
have
emerged
that
leverage
various
reduce
fibroinflammatory
cascade
steatohepatitis
(MASH).
Clinical and Molecular Hepatology,
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 19, 2024
As
the
rates
of
obesity
and
type
2
diabetes
(T2D)
continue
to
increase
globally,
so
does
prevalence
metabolic
dysfunction
associated
steatotic
liver
disease
(MASLD).
Currently,
38%
all
adults
7-14%
children
adolescents
have
MASLD.
By
2040,
MASLD
rate
for
is
projected
over
55%.
Although
many
with
will
not
develop
progressive
disease,
given
vast
number
patients
MASLD,
it
has
now
become
top
indication
transplant
in
United
States
those
hepatocellular
carcinoma
(HCC)
women.
However,
most
common
cause
mortality
among
remains
death
cardiovascular
diseases.
In
addition
outcomes
(cirrhosis
HCC),
increased
risk
developing
de-novo
T2D,
chronic
kidney
sarcopenia
extrahepatic
cancers.
Furthermore,
decreased
health
related
quality
life,
work
productivity,
fatigue
healthcare
resource
utilization
substantial
economic
burden.
Similar
other
lifestyle
interventions
heathy
diet
physical
activity
remain
cornerstone
managing
these
patients.
a
T2D
drugs
are
available
treat
co-morbid
Resmetirom
only
MASH-targeted
medication
that
was
recently
approved
by
Federal
Drug
Administration
use
stage
2-3
fibrosis.
The
following
review
provides
an
overview
epidemiology,
its
factors
demonstrates
without
further
global
initiatives,
may
increase.
Frontiers in Cell and Developmental Biology,
Год журнала:
2024,
Номер
12
Опубликована: Июль 16, 2024
Metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD),
previously
known
as
non-alcoholic
fatty
(NAFLD),
is
the
most
common
disorder
worldwide,
with
an
estimated
global
prevalence
of
more
than
31%.
steatohepatitis
(MASH),
formerly
(NASH),
a
progressive
form
MASLD
characterized
by
hepatic
steatosis,
inflammation,
and
fibrosis.
This
review
aims
to
provide
comprehensive
analysis
extrahepatic
manifestations
MASH,
focusing
on
chronic
diseases
related
cardiovascular,
muscular,
renal
systems.
A
systematic
published
studies
literature
was
conducted
summarize
findings
systemic
impacts
MASH.
The
focused
association
MASH
metabolic
comorbidities,
cardiovascular
mortality,
sarcopenia,
kidney
disease.
Mechanistic
insights
into
concept
lipotoxic
inflammatory
"spill
over"
from
MASH-affected
were
also
explored.
are
highly
associated
(50%-80%)
other
comorbidities
such
impaired
insulin
response,
type
2
diabetes,
dyslipidemia,
hypertriglyceridemia,
hypertension.
Furthermore,
90%
obese
patients
diabetes
have
Data
suggest
that
in
middle-aged
individuals
(especially
those
aged
45-54),
independent
risk
factor
for
plays
crucial
role
mediating
pathological
effects
observed.
Understanding
multifaceted
impact
heart,
muscle,
early
detection
stratification.
knowledge
timely
implementing
management
strategies
addressing
multi-organ
involvement
pathogenesis.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Май 10, 2024
Abstract
Lanifibranor,
a
pan-PPAR
agonist,
improves
liver
histology
in
patients
with
metabolic
dysfunction-associated
steatohepatitis
(MASH),
who
have
poor
cardiometabolic
health
(CMH)
and
cardiovascular
events
as
major
mortality
cause.
NATIVE
trial
secondary
exploratory
outcomes
(ClinicalTrials.gov
NCT03008070)
were
analyzed
for
the
effect
of
lanifibranor
on
IR,
lipid
glucose
metabolism,
systemic
inflammation,
blood
pressure
(BP),
hepatic
steatosis
(imaging
histological
grading)
all
original
analysis.
With
lanifibranor,
triglycerides,
HDL-C,
apolipoproteins,
insulin,
HOMA-IR,
HbA1c,
fasting
(FG),
hs-CRP,
ferritin,
diastolic
BP
improved
significantly,
independent
diabetes
status:
most
prediabetes
returned
to
normal
FG
levels.
Significant
adiponectin
increases
correlated
CMH
marker
improvement;
had
an
average
weight
gain
2.5
kg,
49%
gaining
≥2.5%
weight.
Therapeutic
benefits
similar
regardless
change.
Here,
we
show
that
effects
MASH
are
accompanied
improvement,
indicative
potential
clinical
benefits.
Hepatology Communications,
Год журнала:
2025,
Номер
9(2)
Опубликована: Янв. 29, 2025
The
prevalence
of
metabolic
dysfunction–associated
steatotic
liver
disease
(MASLD),
which
is
increasingly
being
recognized
as
a
leading
cause
chronic
pathology
globally,
increasing.
pathophysiological
underpinnings
its
progression,
currently
under
active
investigation,
involve
oxidative
stress.
Human
adipose
tissue,
an
integral
endocrine
organ,
secretes
array
adipokines
that
are
modulated
by
dietary
patterns
and
lifestyle
choices.
These
intricately
orchestrate
regulatory
pathways
impact
glucose
lipid
metabolism,
stress,
mitochondrial
function,
thereby
influencing
the
evolution
hepatic
steatosis
progression
to
steatohepatitis
(MASH).
This
review
examines
recent
data,
underscoring
critical
interplay
reactive
oxygen
species,
redox
signaling
in
adipokine-mediated
mechanisms.
role
various
regulating
onset
MASLD/MASH
through
dysfunction
endoplasmic
reticulum
stress
underlying
mechanisms
discussed.
Due
emerging
correlation
between
development
MASLD
positions,
these
potential
targets
for
innovative
therapeutic
interventions
management.
A
comprehensive
understanding
pathogenesis
instrumental
identifying
therapies
MASH.
