Gut microbiota of patients insusceptible to olanzapine-induced fatty liver disease relieves hepatic steatosis in rats
AJP Gastrointestinal and Liver Physiology,
Год журнала:
2025,
Номер
328(2), С. G110 - G124
Опубликована: Янв. 21, 2025
Patients
who
were
less
inclined
to
have
olanzapine-induced
fatty
liver
had
different
gut
microbiota
profiles
than
did
those
in
the
susceptible
cohort.
Lachnospiraceae,
Ruminococcaceae,
Oscillospiraceae,
Butyricicoccaceae,
and
Christensenellaceae
enriched
patients
prone
disease
caused
by
olanzapine.
Fecal
treatment
(FMT)
with
these
fecal
samples
promoted
short-chain
acid
(SCFA)
production,
which
attenuated
circulating
leptin
inhibited
FASN
ACC1,
thereby
suppressing
lipid
synthesis
liver,
ultimately
leading
alleviation
of
hepatic
steatosis.
Язык: Английский
Metabolic effects of atypical antipsychotics: Molecular targets
Journal of Neuroendocrinology,
Год журнала:
2023,
Номер
35(12)
Опубликована: Окт. 4, 2023
Abstract
Atypical
antipsychotics
(AAPs)
are
commonly
prescribed
drugs
in
the
treatment
of
schizophrenia,
bipolar
disorder
and
other
mental
diseases
with
psychotic
traits.
Although
use
AAPs
is
associated
beneficial
effects
these
patients,
they
also
undesired
metabolic
side
effects,
including
syndrome
(MetS).
MeS
defined
by
presence
abnormalities
such
as
large
waist
circumference,
dyslipidemia,
fasting
hyperglycemia
elevated
blood
pressure,
which
predispose
to
type
2
diabetes
(T2D)
cardiovascular
disease.
In
this
review,
molecular
cellular
mechanisms
involved
induced
described.
These
complex
have
multiple
targets
significantly
affect
activities
several
hormones
neuromodulators.
Additionally,
all
relevant
organs,
namely
liver,
pancreas,
adipose
tissue,
skeletal
muscle
intestine,
central
peripheral
nervous
system
well.
A
better
understanding
linking
MetS
responsible
for
clinically
different
distinct
needed.
This
knowledge
will
help
development
novel
less
adverse
well
adjuvant
therapies
patients
receiving
AAPs.
Язык: Английский
Farrerol alleviates insulin resistance and hepatic steatosis of metabolic associated fatty liver disease by targeting PTPN1
Journal of Cellular and Molecular Medicine,
Год журнала:
2024,
Номер
28(18)
Опубликована: Сен. 1, 2024
Metabolic
associated
fatty
liver
disease
(MAFLD)
is
the
most
common
chronic
worldwide,
characterized
by
excess
lipid
deposition.
Insulin
resistance
(IR)
serves
as
a
fundamental
pathogenic
factor
in
MAFLD.
However,
currently,
there
are
no
approved
specific
agents
for
its
treatment.
Farrerol,
novel
compound
with
antioxidant
and
anti-inflammatory
effects,
has
garnered
significant
attention
recent
years
due
to
hepatoprotective
properties.
Despite
this,
precise
underlying
mechanisms
of
action
remain
unclear.
In
this
study,
network
pharmacology
approach
predicted
protein
tyrosine
phosphatase
non-receptor
type
1
(PTPN1)
potential
target
farrerol's
liver.
Subsequently,
administration
farrerol
improved
insulin
sensitivity
glucose
tolerance
MAFLD
mice.
Furthermore,
alleviated
accumulation
binding
PTPN1
reducing
dephosphorylation
receptor
(INSR)
HepG2
cells
Thus,
phosphoinositide
3-kinase/serine/threonine-protein
kinases
(PI3K/AKT)
signalling
pathway
was
active,
leading
downstream
reduction.
Overall,
study
demonstrates
that
alleviates
hepatic
steatosis
targeting
PTPN1.
Язык: Английский
Estrogens prevent the hypothalamus-periphery crosstalk induced by olanzapine intraperitoneal treatment in female mice: Effects on brown/beige adipose tissues and liver
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease,
Год журнала:
2024,
Номер
1870(5), С. 167227 - 167227
Опубликована: Май 11, 2024
Olanzapine
(OLA)
is
a
highly
obesogenic
second-generation
antipsychotic
(SGA).
Recently
we
demonstrated
that,
contrarily
to
OLA
oral
treatment,
intraperitoneal
(i.p.)
administration
resulted
in
weight
loss
and
absence
of
hepatic
steatosis
wild-type
(WT)
protein
tyrosine
phosphatase
1B
(PTP1B)-deficient
(KO)
male
mice.
This
protection
relied
on
two
central-peripheral
axes
connecting
hypothalamic
AMPK
with
brown/inguinal
white
adipose
tissue
(BAT/iWAT)
uncoupling
protein-1
(UCP-1)
JNK
fatty
acid
synthase
(FAS).
Herein,
addressed
i.p.
treatment
effects
WT
PTP1B-KO
female
Contrarily
our
previous
results
females
receiving
orally,
the
did
not
induce
gain
or
hyperphagia.
Molecularly,
failed
diminish
phospho-AMPK
elevate
BAT
UCP-1
energy
expenditure
(EE)
despite
preservation
iWAT
browning.
Conversely,
ovariectomized
mice
reduced
phospho-AMPK,
increased
BAT/iWAT
EE,
induced
as
occurred
males.
Pretreatment
neurons
17β-estradiol
(E
Язык: Английский
Vitamin D Receptor Activation Attenuates Olanzapine‐Induced Dyslipidemia in Mice Through Alleviating Hepatic Endoplasmic Reticulum Stress
Advanced Biology,
Год журнала:
2023,
Номер
7(12)
Опубликована: Авг. 10, 2023
Abstract
The
involvement
of
vitamin
D
(VD)
signaling
in
atypical
antipsychotics
(AAPs)‐induced
metabolic
disturbances
has
been
previously
established.
This
study
aims
to
elucidate
the
role
VD
maintaining
endoplasmic
reticulum
(ER)
homeostasis
and
its
impact
on
AAPs‐induced
adverse
effects.
Female
C57BL/6
mice
receive
either
calcitriol
or
vehicle
one
week
prior
co‐treatment
with
olanzapine
(OLZ)
for
an
additional
four
weeks.
Metabolic
parameters,
hepatic
ER
homeostasis,
SREBPs
pathway
are
assessed
through
biochemical
assays
protein
expression
profiling.
HepG2
cells
transfected
receptor
(VDR)
siRNA
VDR
knockdown.
OLZ‐treated
exposed
examine
effects
unfolded
response
(UPR)
pathways.
activation
by
reduces
OLZ‐induced
stress,
leading
decreased
activity
lipid
accumulation.
Conversely,
knockdown
diminishes
protective
against
stress
activation.
resulted
sustained
UPR
activation,
elevated
cleaved
levels,
increased
These
findings
highlight
essential
beneficial
side
Targeting
resolve
is
likely
applicable
therapeutic
strategy
disturbances.
Язык: Английский