bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 19, 2024
Abstract
Obesity
is
a
global
health
crisis
that
contributes
to
morbidity
and
mortality
worldwide.
Obesity’s
comorbid
association
with
variety
of
diseases,
from
metabolic
syndrome
neurodegenerative
disease,
underscores
the
critical
need
better
understand
pathobiology
obesity.
Adipose
tissue,
once
seen
as
an
inert
storage
depot,
now
recognized
active
endocrine
organ,
regulating
systemic
homeostasis.
Recent
studies
spotlight
theranostic
utility
extracellular
vesicles
(EVs)
novel
biomarkers
drivers
including
obesity-related
complications.
Adipose-derived
EVs
(ADEVs)
have
garnered
increased
interest
for
their
roles
in
diverse
however
robust
isolation
characterization
protocols
human,
cell-specific
EV
subsets
are
limited.
Herein,
we
directly
address
this
technical
challenge
by
establishing
multiparametric
analysis
framework
leverages
bulk
single
characterization,
mRNA
phenotyping
proteomics
human
ADEVs
paired
visceral
adipose
cultured
mature
adipocyte
conditioned
media,
plasma
obese
subjects
undergoing
bariatric
surgery.
Importantly,
rigorous
at
tissue
level
identified
top
‘adipose
liquid
biopsy’
candidates
were
validated
circulating
same
patient.
In
summary,
our
study
paves
way
toward
cell-specific,
studying
obesity-driven
disease.
Cell,
Год журнала:
2024,
Номер
187(16), С. 4129 - 4143
Опубликована: Июль 26, 2024
Obesity
causes
significant
morbidity
and
mortality
globally.
Research
in
the
last
three
decades
has
delivered
a
step-change
our
understanding
of
fundamental
mechanisms
that
regulate
energy
homeostasis,
building
on
foundational
discoveries
mouse
models
metabolic
disease.
However,
not
all
findings
made
rodents
have
translated
to
humans,
hampering
drug
discovery
this
field.
Here,
we
review
how
studies
mice
humans
informed
current
framework
for
discuss
their
challenges
limitations,
offer
perspective
human
may
play
an
increasingly
important
role
disease
identification
therapeutic
targets
future.
Experimental & Molecular Medicine,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 13, 2025
Abstract
Hepatic
endoplasmic
reticulum
(ER)
stress
is
implicated
in
the
development
of
steatosis
and
its
progression
to
nonalcoholic
steatohepatitis
(NASH).
The
ER
liver
can
sustain
metabolic
function
by
activating
defense
mechanisms
that
delay
or
prevent
fatty
disease
(NAFLD).
However,
precise
which
response
protects
against
NAFLD
remain
largely
unknown.
Recently,
activin
E
has
been
linked
diseases
such
as
insulin
resistance
NAFLD.
physiological
conditions
regulatory
driving
hepatic
Inhbe
expression
(which
encodes
E)
well
role
require
further
investigation.
Here
we
found
increased
under
prolonged
fasting
conditions,
was
mediated
ATF4,
determined
promoter
analysis
a
mouse
model.
Consistently,
positive
correlation
between
INHBE
ATF4
levels
relation
status
confirmed
using
public
human
datasets.
To
investigate
steatosis,
assessed
fluxes
lipid
metabolism
an
-knockout
These
mice
displayed
lean
phenotype
but
developed
severe
high-fat
diet.
deficiency
resulted
lipolysis
adipose
tissue,
leading
acid
influx
into
liver.
Conversely,
overexpression
ameliorated
suppressing
tissue
through
ALK7–Smad
signaling.
In
conclusion,
serves
hepatokine
prevents
liver,
thereby
protecting
Circulation Research,
Год журнала:
2025,
Номер
136(11), С. 1476 - 1493
Опубликована: Май 22, 2025
Cardiovascular-kidney-metabolic
syndrome
is
a
progressive
disorder
driven
by
perturbed
interorgan
crosstalk
among
adipose,
liver,
kidney,
and
heart,
leading
to
multiorgan
dysfunction.
Capturing
the
complexity
of
human
cardiovascular-kidney-metabolic
pathophysiology
using
conventional
models
has
been
challenging.
Multi-organ-on-a-chip
platforms
offer
versatile
means
study
underlying
signaling
at
different
stages
bolster
clinical
translation.