Molecular Metabolism,
Journal Year:
2024,
Volume and Issue:
91, P. 102067 - 102067
Published: Nov. 14, 2024
Infiltration
of
adipocytes
into
the
pancreatic
parenchyma
has
been
linked
to
impaired
insulin
secretion
in
individuals
with
increased
genetic
risk
T2D
and
prediabetic
conditions.
However,
study
this
ectopic
fat
depot
limited
by
lack
suitable
vitro
models.
Here,
we
developed
a
novel
3D
model
functionally
mature
human
adipose
tissue
organoids
aggregating
tissue-derived
stromal
vascular
fraction
(SVF)
cells
differentiating
them
over
19
days.
These
carry
biological
properties
situ
fat,
presenting
levels
adipogenic
markers
comparable
native
improved
lipolytic
anti-lipolytic
response
compared
conventional
2D
cultures.
The
harbour
small
population
immune
cells,
mimicking
vivo
environment.
Furthermore,
they
express
GIPR,
allowing
investigation
incretin
effects
fat.
In
accordance,
GIP
dual
GLP1R/GIPR
agonist
tirzepatide
stimulate
lipolysis
but
had
distinct
on
expression
proinflammatory
cytokines.
This
organoid
is
valuable
tool
metabolic
impact
signalling
tissue,
revealing
potential
therapeutic
targets
incretins
beyond
islets.
donor-specific
memory
these
enables
examination
fat-islet
crosstalk
donor-related
context.
Diabetes Obesity and Metabolism,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 26, 2024
Abstract
Obesity
is
a
chronic
condition
demanding
effective
treatment
strategies,
among
which
pharmacotherapy
plays
critical
role.
As
glucagon‐like
peptide‐1
(GLP‐1)
agonist
approved
by
the
Food
and
Drug
Administration
(FDA)
for
long‐term
weight
management
in
adults
with
obesity,
liraglutide
semaglutide
have
great
loss
effect
through
reducing
food
intake
delaying
gastric
emptying.
The
emergence
of
unimolecular
polypharmacology,
utilizes
single
molecules
to
simultaneously
target
multiple
receptors
or
pathways,
marked
revolutionary
improvement
GLP‐1‐based
obesity
pharmacotherapy.
dual
tirzepatide
activates
both
GLP‐1
glucose‐dependent
insulinotropic
polypeptide
(GIP)
has
shown
enhanced
potency
compared
conventional
mono
agonist.
Furthermore,
emerging
data
suggests
that
GLP‐1/glucagon
(GCG)
agonist,
as
well
GLP‐1/GIP/GCG
triple
may
offer
superior
efficacy
over
This
review
summarizes
comprehensive
mechanisms
underlying
pronounced
advantages
GLP‐1/GIP
GLP‐1/GCG
reduction
obese
without
type
2
diabetes.
A
deeper
understanding
these
multitargeting
agonists
will
provide
insights
their
clinical
application
guide
development
new
drugs
treatment.
Expert Opinion on Pharmacotherapy,
Journal Year:
2024,
Volume and Issue:
unknown, P. 1 - 19
Published: Dec. 4, 2024
Introduction
Tirzepatide
is
a
once-weekly
dual
agonist,
acting
on
glucagon-like
peptide-1
(GLP-1)
and
glucose-dependent
insulinotropic
polypeptide
(GIP)
receptors.
It
approved
at
the
same
doses
(5,
10
15
mg)
for
both
type
2
diabetes
(T2D)
chronic
weight
management.
Trends in Endocrinology and Metabolism,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 1, 2024
Obesity
is
a
major
global
health
issue
with
various
metabolic
complications.
Both
bariatric
surgery
and
dieting
achieve
weight
loss
improve
whole-body
metabolism,
but
vary
in
their
ability
to
maintain
these
improvements
over
time.
Adipose
tissue
skeletal
muscle
metabolism
are
crucial
regulation,
obesity
linked
mitochondrial
dysfunction
both
tissues.
The
impact
of
versus
on
adipose
remains
be
elucidated.
Understanding
the
molecular
pathways
that
modulate
following
holds
potential
for
identifying
novel
therapeutic
targets
management.
This
narrative
review
summarizes
current
knowledge
diet-induced
muscle,
sheds
light
respective
effects.
Journal of Diabetes Investigation,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 30, 2024
There
are
several
physiological
and
pharmacological
actions
of
glucagon-like
peptide-1
glucose-dependent
insulinotropic
polypeptide/gastric
inhibitory
polypeptide
for
the
regulation
blood
glucose
bodyweight.
Molecular Metabolism,
Journal Year:
2024,
Volume and Issue:
91, P. 102067 - 102067
Published: Nov. 14, 2024
Infiltration
of
adipocytes
into
the
pancreatic
parenchyma
has
been
linked
to
impaired
insulin
secretion
in
individuals
with
increased
genetic
risk
T2D
and
prediabetic
conditions.
However,
study
this
ectopic
fat
depot
limited
by
lack
suitable
vitro
models.
Here,
we
developed
a
novel
3D
model
functionally
mature
human
adipose
tissue
organoids
aggregating
tissue-derived
stromal
vascular
fraction
(SVF)
cells
differentiating
them
over
19
days.
These
carry
biological
properties
situ
fat,
presenting
levels
adipogenic
markers
comparable
native
improved
lipolytic
anti-lipolytic
response
compared
conventional
2D
cultures.
The
harbour
small
population
immune
cells,
mimicking
vivo
environment.
Furthermore,
they
express
GIPR,
allowing
investigation
incretin
effects
fat.
In
accordance,
GIP
dual
GLP1R/GIPR
agonist
tirzepatide
stimulate
lipolysis
but
had
distinct
on
expression
proinflammatory
cytokines.
This
organoid
is
valuable
tool
metabolic
impact
signalling
tissue,
revealing
potential
therapeutic
targets
incretins
beyond
islets.
donor-specific
memory
these
enables
examination
fat-islet
crosstalk
donor-related
context.
