Abstract
Background
Metabolic
disorders
have
become
one
of
the
global
medical
problems.
Due
to
complexity
its
pathogenesis,
there
is
still
no
effective
treatment.
Bile
acids
(BAs)
and
gut
microbiota
(GM)
been
proved
be
closely
related
host
metabolism,
which
could
important
targets
for
metabolic
disorders.
Zhi-Kang-Yin
(ZKY)
a
traditional
Chinese
medicine
(TCM)
formula
developed
by
research
team
according
theory
TCM
has
shown
improve
metabolism
in
clinic.
However,
underlying
mechanisms
are
unclear.
Aim
study
This
aimed
investigate
potential
beneficial
effect
ZKY
on
metabolism.
Methods
High-fat
diet
(HFD)-fed
mice
were
treated
with
without
ZKY.
The
glucose
lipid
metabolism-related
indexes
measured.
BA
profile,
GM
composition
hepatic
transcriptome
then
investigated
analyze
changes
BAs,
GM,
gene
expression.
Moreover,
relationship
between
BAs
was
identified
functional
quantification
ex
vivo
fermentation
experiment.
Results
reduced
weight
gain
levels
both
liver
serum,
attenuated
steatosis
improved
tolerance
HFD-fed
mice.
profile
detection
showed
that
changed
increased
proportion
unconjugated
non-12-OH
BAs.
Hepatic
transcriptomic
analysis
revealed
fatty
acid
biosynthesis
pathways
regulated.
In
addition,
significantly
structure
upregulated
copy
number
bacterial
bile
salt
hydrolase.
Meanwhile,
directly
promoted
growth
Bifidobacterium
,
well-known
hydrolase
-
producing
genus.
co-culture
experiment
demonstrated
group
mediated
ZKY-shifted
led
expression
genes
associated
degradation
liver.
Conclusion
Our
indicated
improving
modulation
GM-BAs
axis,
especially,
upregulating
abundance
hydrolase-expression
bacteria
increasing
indicates
axis
might
an
pathway
The
identification
of
mechanisms
to
store
glucose
carbon
in
the
form
glycogen
rather
than
fat
hepatocytes
has
important
implications
for
prevention
nonalcoholic
fatty
liver
disease
(NAFLD)
and
other
chronic
metabolic
diseases.
In
this
work,
we
show
that
glycogenesis
uses
its
intermediate
metabolite
uridine
diphosphate
(UDPG)
antagonize
lipogenesis,
thus
steering
both
mouse
human
toward
storing
as
glycogen.
underlying
mechanism
involves
transport
UDPG
Golgi
apparatus,
where
it
binds
site-1
protease
(S1P)
inhibits
S1P-mediated
cleavage
sterol
regulatory
element-binding
proteins
(SREBPs),
thereby
inhibiting
lipogenesis
hepatocytes.
Consistent
with
mechanism,
administration
is
effective
at
treating
NAFLD
a
model
organoids.
These
findings
indicate
potential
opportunity
ameliorate
disordered
metabolism
liver.
Medicinal Research Reviews,
Год журнала:
2023,
Номер
44(2), С. 568 - 586
Опубликована: Окт. 30, 2023
Abstract
Nonalcoholic
fatty
liver
disease,
also
called
metabolic
dysfunction‐associated
steatotic
is
the
most
common
disease
worldwide
and
has
no
approved
pharmacotherapy.
Due
to
its
beneficial
effects
on
regulation,
inflammation
suppression,
cell
death
prevention,
fibrogenesis
inhibition,
farnesoid
X
receptor
(FXR)
widely
accepted
as
a
promising
therapeutic
target
for
nonalcoholic
steatosis
(NASH)
or
steatohepatitis
(MASH).
Many
FXR
agonists
have
been
developed
NASH/MASH
therapy.
Obeticholic
acid
(OCA)
pioneering
frontrunner
agonist
first
demonstrating
success
in
clinical
trials.
Unfortunately,
OCA
did
not
receive
regulatory
approval
NASH
pharmacotherapy
because
moderate
benefits
outweigh
safety
risks,
which
may
cast
shadow
over
FXR‐based
drug
development
NASH/MASH.
This
review
summarizes
milestones
of
discuss
limitations,
including
hepatoprotection
undesirable
side
dyslipidemia,
pruritus,
cholelithiasis,
toxicity
risk,
depth.
More
importantly,
we
provide
perspectives
therapy
NASH/MASH,
hoping
support
successful
bench‐to‐clinic
transition.
Abstract
The
gut
microbiota
plays
a
critical
role
in
maintaining
human
health,
influencing
wide
range
of
physiological
processes,
including
immune
regulation,
metabolism,
and
neurological
function.
Recent
studies
have
shown
that
imbalances
composition
can
contribute
to
the
onset
progression
various
diseases,
such
as
metabolic
disorders
(e.g.,
obesity
diabetes)
neurodegenerative
conditions
Alzheimer's
Parkinson's).
These
are
often
accompanied
by
chronic
inflammation
dysregulated
responses,
which
closely
linked
specific
forms
cell
death,
pyroptosis
ferroptosis.
Pathogenic
bacteria
trigger
these
death
pathways
through
toxin
release,
while
probiotics
been
found
mitigate
effects
modulating
responses.
Despite
insights,
precise
mechanisms
influences
diseases
remain
insufficiently
understood.
This
review
consolidates
recent
findings
on
impact
immune‐mediated
inflammation‐associated
conditions.
It
also
identifies
gaps
current
research
explores
potential
advanced
technologies,
organ‐on‐chip
models
microbiome–gut–organ
axis,
for
deepening
our
understanding.
Emerging
tools,
single‐bacterium
omics
spatial
metabolomics,
discussed
their
promise
elucidating
microbiota's
disease
development.
Journal of Advanced Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 1, 2024
Inflammatory
bowel
disease
(IBD)
is
a
global
with
limited
therapy.
It
reported
that
sedanolide
exerts
anti-oxidative
and
anti-inflammatory
effects
as
natural
phthalide,
but
its
on
IBD
remain
unclear.
In
this
study,
we
investigated
the
impacts
of
dextran
sodium
sulfate
(DSS)-induced
colitis
in
mice.
The
mice
were
administered
or
vehicle
followed
by
DSS
administration,
after
which
symptoms,
inflammation
levels,
intestinal
barrier
function
evaluated.
Transcriptome
analysis,
16S
rRNA
sequencing,
targeted
metabolomics
analysis
bile
acids
lipids
performed.
Sedanolide
protected
from
DSS-induced
colitis,
suppressed
inflammation,
restored
weakened
epithelial
barrier,
modified
gut
microbiota
decreasing
salt
hydrolase
(BSH)-expressing
bacteria.
downregulation
BSH
activity
increased
ratio
conjugated/unconjugated
(BAs),
thereby
inhibiting
farnesoid
X
receptor
(FXR)
pathway.
roles
FXR
pathway
verified
using
an
FXR-specific
agonist
(fexaramine)
germ-free
mice,
respectively.
Furthermore,
identified
key
effector
ceramide,
regulated
sphingomyelin
phosphodiesterase
3
(SMPD3).
protective
ceramide
(d18:1/16:0)
against
demonstrated
vitro
human
cell
line
Caco-2.
could
reshape
flora
influence
BA
composition,
thus
FXR-SMPD3
to
stimulate
synthesis
ultimately
alleviated
Overall,
our
research
revealed
indicated
may
be
clinical
treatment
for
colitis.
Additionally,
lipid
was
shown
mediate
sedanolide,
providing
new
insight
into
associations
between
metabolites.
Cell Death Discovery,
Год журнала:
2024,
Номер
10(1)
Опубликована: Май 15, 2024
Abstract
Ferroptosis
is
a
novel
form
of
lipid
peroxidation-driven,
iron-dependent
programmed
cell
death.
Various
metabolic
pathways,
including
those
involved
in
and
iron
metabolism,
contribute
to
ferroptosis
regulation.
The
gut
microbiota
not
only
supplies
nutrients
energy
the
host,
but
also
plays
crucial
role
immune
modulation
balance.
In
this
review,
we
explore
pathways
associated
with
impact
on
host
metabolism.
We
subsequently
summarize
recent
studies
influence
regulation
by
discuss
potential
mechanisms
through
which
affects
ferroptosis.
Additionally,
conduct
bibliometric
analysis
relationship
between
context
chronic
kidney
disease.
This
can
provide
new
insights
into
current
research
status
future
microbiota.
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Март 21, 2024
Non-alcoholic
fatty
liver
disease
(NAFLD)
is
the
most
common
chronic
disease,
resulting
in
a
huge
medical
burden
worldwide.
Accumulating
evidence
suggests
that
gut
microbiome
and
bile
acids
play
pivotal
roles
during
development
of
NAFLD.
Patients
with
NAFLD
exhibit
unique
signatures
intestinal
marked
by
priority
Gram-negative
bacteria,
decreased
ratio
Frontiers in Endocrinology,
Год журнала:
2024,
Номер
15
Опубликована: Июль 4, 2024
Non-alcoholic
fatty
liver
disease
(NAFLD)
is
a
prevalent
and
significant
global
public
health
issue.
Nonalcoholic
steatohepatitis
(NASH)
represents
an
advanced
stage
of
NAFLD
in
terms
pathology.
However,
the
intricate
mechanisms
underlying
progression
from
to
NASH
remain
elusive.
Ferroptosis,
characterized
by
iron-dependent
cell
death
distinguished
other
forms
based
on
morphological,
biochemical,
genetic
criteria,
has
emerged
as
potential
participant
with
pivotal
role
driving
progression.
Nevertheless,
its
precise
mechanism
remains
poorly
elucidated.
In
this
review
article,
we
comprehensively
summarize
pathogenesis
NAFLD/NASH
ferroptosis
while
highlighting
recent
advances
understanding
mechanistic
involvement
NAFLD/NASH.