NAD+ prevents chronic kidney disease by activating renal tubular metabolism
JCI Insight,
Год журнала:
2025,
Номер
10(5)
Опубликована: Март 9, 2025
Chronic
kidney
disease
(CKD)
is
associated
with
renal
metabolic
disturbances,
including
impaired
fatty
acid
oxidation
(FAO).
Nicotinamide
adenine
dinucleotide
(NAD+)
a
small
molecule
that
participates
in
hundreds
of
metabolism-related
reactions.
NAD+
levels
are
decreased
CKD,
and
supplementation
protective.
However,
both
the
mechanism
how
protects
from
as
well
cell
types
involved,
poorly
understood.
Using
mouse
model
Alport
syndrome,
we
show
nicotinamide
riboside
(NR),
an
precursor,
stimulated
PPARα
signaling
restored
FAO
proximal
tubules,
thereby
protecting
CKD
sexes.
Bulk
RNA-sequencing
showed
pathways
were
mice
activated
by
NR
These
transcriptional
changes
confirmed
orthogonal
imaging
techniques
biochemical
assays.
Single-nuclei
RNA
sequencing
spatial
transcriptomics,
first
their
kind
to
our
knowledge
mice,
tubule
cells.
Finally,
also
report,
for
time
knowledge,
sex
differences
at
level
this
model.
In
summary,
data
herein
identify
nephroprotective
they
demonstrate
benefit
localizes
Язык: Английский
Nicotinamide riboside activates renal metabolism and protects the kidney in a model of Alport syndrome
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 29, 2024
ABSTRACT
Chronic
kidney
disease
(CKD)
is
associated
with
renal
metabolic
disturbances,
including
impaired
fatty
acid
oxidation
(FAO).
Nicotinamide
adenine
dinucleotide
(NAD
+
)
a
small
molecule
that
participates
in
hundreds
of
metabolism-related
reactions.
NAD
levels
are
decreased
CKD,
and
supplementation
protective.
However,
both
the
mechanism
how
protects
from
as
well
cell
types
involved,
poorly
understood.
Using
mouse
model
Alport
syndrome,
we
show
nicotinamide
riboside
(NR),
an
precursor,
stimulates
peroxisome
proliferator-activated
receptor
alpha
signaling
restores
FAO
proximal
tubules,
thereby
protecting
CKD
sexes.
Bulk
RNA-sequencing
shows
pathways
mice
activated
by
NR
These
transcriptional
changes
confirmed
orthogonal
imaging
techniques
biochemical
assays.
Single
nuclei
spatial
transcriptomics,
first
their
kind
mice,
tubule
cells.
Finally,
also
report,
for
time,
sex
differences
at
level
this
model.
In
summary,
identify
nephroprotective
demonstrate
cells
substantially
contribute
to
benefit.
Язык: Английский