Nature Metabolism,
Год журнала:
2023,
Номер
5(3), С. 385 - 397
Опубликована: Март 6, 2023
Abstract
Depriving
cells
of
nutrients
triggers
an
energetic
crisis,
which
is
resolved
by
metabolic
rewiring
and
organelle
reorganization.
Primary
cilia
are
microtubule-based
organelles
at
the
cell
surface,
capable
integrating
multiple
signalling
cues,
but
their
precise
sensory
function
not
fully
understood.
Here
we
show
that
primary
respond
to
nutrient
availability
adjust
length
via
glutamine-mediated
anaplerosis
facilitated
asparagine
synthetase
(ASNS).
Nutrient
deprivation
causes
elongation,
mediated
reduced
mitochondrial
function,
ATP
AMPK
activation
independently
mTORC1.
Of
note,
glutamine
removal
replenishment
necessary
sufficient
induce
ciliary
elongation
or
retraction,
respectively,
under
stress
conditions
both
in
vivo
vitro
restoring
ASNS-dependent
glutamate
generation.
Ift88-mutant
lacking
glutamine-dependent
during
stress,
due
expression
activity
ASNS
base
cilia.
Our
data
indicate
a
role
for
responding
to,
possibly
sensing,
cellular
levels
stress.
Clinical Journal of the American Society of Nephrology,
Год журнала:
2020,
Номер
15(4), С. 577 - 584
Опубликована: Фев. 21, 2020
Autosomal
dominant
polycystic
kidney
disease
is
characterized
by
progressive
development
and
enlargement
of
cysts,
leading
to
ESKD.
Because
the
kidneys
are
under
high
metabolic
demand,
it
not
surprising
that
mounting
evidence
suggests
a
defect
exists
in
vitro
animal
models
autosomal
disease,
which
likely
contributes
cystic
epithelial
proliferation
subsequent
cyst
growth.
Alterations
include
defective
glucose
metabolism
(reprogramming
favor
aerobic
glycolysis),
dysregulated
lipid
amino
acid
metabolism,
impaired
autophagy,
mitochondrial
dysfunction.
Limited
supports
cellular
also
humans
with
disease.
There
notable
overlapping
features
pathways
among
obesity,
and/or
Both
dietary
pharmacologic-based
strategies
targeting
abnormalities
being
considered
as
therapies
slow
progression
attractive,
particularly
given
slowly
nature
Dietary
daily
caloric
restriction,
intermittent
fasting,
time-restricted
feeding,
ketogenic
diet,
2-deoxy-glucose
well
alterations
nutrient
availability.
Pharmacologic-based
AMP-activated
kinase
activators,
sodium
cotransporter-2
inhibitors,
niacinamide,
thiazolidenediones.
The
results
from
initial
clinical
trials
upcoming
anxiously
awaited
within
scientific
communities.
continues
be
need
for
additional
mechanistic
studies
better
understand
role
translation
trials.
Beyond
single-intervention
focused
on
reprograming
great
potential
combining
metabolic-focused
therapeutic
approaches
compounds
other
signaling
cascades
altered
such
tolvaptan.
Cellular Signalling,
Год журнала:
2019,
Номер
67, С. 109495 - 109495
Опубликована: Дек. 6, 2019
Autosomal
Dominant
Polycystic
Kidney
Disease
(ADPKD)
is
a
slowly
progressive
disease
characterized
by
the
relentless
growth
of
renal
cysts
throughout
life
affected
individuals.
Early
evidence
suggested
that
epithelia
lining
share
neoplastic
features,
leading
to
definition
PKD
as
"neoplasm
in
disguise".
Recent
work
from
our
and
other
laboratories
has
identified
profound
metabolic
reprogramming
PKD,
similar
one
reported
cancer
consistent
with
increased
proliferation.
Multiple
lines
suggest
aerobic
glycolysis
(a
Warburg-like
effect)
present
disease,
along
dysfunctions
such
an
increase
pentose
phosphate
pathway,
glutamine
anaplerosis
fatty
acid
biosynthesis,
while
oxidation
oxidative
phosphorylation
(OXPHOS)
are
decreased.
In
addition
glutamine,
amino
acid-related
pathways
appear
altered,
including
asparagine
arginine.
The
precise
origin
alterations
not
entirely
clear,
but
two
hypotheses
can
be
formulated,
mutually
exclusive.
First,
polycystins
have
been
recently
shown
regulate
directly
mitochondrial
function
structure
either
regulating
Ca2+
uptake
mitochondria
at
Mitochondria
Associated
Membranes
(MAMs)
Endoplasmic
Reticulum,
or
direct
translocation
small
fragment
protein
into
matrix
mitochondria.
One
alternative
possibility
ADPKD
secondary
de-regulation
proliferation,
driven
multiple
signaling
which
include
mTORC1
AMPK
among
most
relevant.
While
mechanisms
underlying
these
novel
will
need
further
investigation,
it
evident
they
offer
great
opportunity
for
interventions
disease.
Atherosclerosis
is
a
chronic
inflammatory
disease
that
can
cause
acute
cardiovascular
events.
Activation
of
the
NOD-like
receptor
family,
pyrin
domain
containing
protein
3
(NLRP3)
inflammasome
enhances
atherogenesis,
which
links
lipid
metabolism
to
sterile
inflammation.
This
study
examines
impact
an
endogenous
metabolite,
namely
ketone
body
3-hydroxybutyrate
(3-HB),
on
mouse
model
atherosclerosis.
It
found
daily
oral
administration
3-HB
significantly
ameliorate
Mechanistically,
reduce
M1
macrophage
proportion
and
promote
cholesterol
efflux
by
acting
macrophages
through
its
G-protein-coupled
109a
(Gpr109a).
3-HB-Gpr109a
signaling
promotes
extracellular
calcium
(Ca2+)
influx.
The
elevation
intracellular
Ca2+
level
reduces
release
from
endothelium
reticulum
(ER)
mitochondria,
thus
inhibits
ER
stress
triggered
store
depletion.
As
NLRP3
be
activated
stress,
inhibit
activation
inflammasome,
triggers
increase
inhibition
efflux.
concluded
nutritional
supplementation
attenuates
atherosclerosis
in
mice.
