Effects of 17,18-Epoxyeicosatetraenoic Acid and Epoxydocosapentaenoic Acid Combined with Soluble Epoxide Hydrolase Inhibitor t-TUCB on Brown Adipogenesis and Mitochondrial Respiration
Nutrients,
Год журнала:
2025,
Номер
17(6), С. 936 - 936
Опубликована: Март 7, 2025
Background/Objectives:
17,18-epoxyeicosatetraenoic
acid
(17,18-EEQ)
and
19,20-epoxydocosapentaenoic
(19,20-EDP)
are
bioactive
metabolites
produced
from
eicosapentaenoic
(EPA)
docosahexaenoic
(DHA),
respectively,
by
CYP450s.
These
unstable
quickly
metabolized
auto-oxidation,
esterification,
β-oxidation,
or
hydrolysis
soluble
epoxide
hydrolase
(sEH).
17,18-EEQ
19,20-EDP
combined
with
a
potent
sEH
inhibitor
t-TUCB
differentially
activated
brown
adipose
tissue
in
diet-induced
obesity.
In
the
current
study,
we
investigated
whether
these
n-3
epoxy
fatty
acids
directly
promote
adipocyte
differentiation
their
thermogenic
capacities.
Methods:
Murine
preadipocytes
were
treated
during
post
differentiation.
Brown
marker
protein
expression
mitochondrial
respiration
measured.
addition,
activation
of
PPARγ
suppression
NFκB
reporter
alone
assessed,
roles
evaluated
knockdown
GW9662.
Results:
promoted
adipogenesis
uncoupling.
Moreover,
t-TUCB,
both
epoxides
improved
respiration,
but
only
significantly
increased
uncoupling
(and
heat
production)
differentiated
adipocytes.
may
be
required
for
effects
on
not
function
Conclusions:
The
results
demonstrate
that,
also
promotes
thermogenesis
Together,
suggest
potentials
tested
epoxides,
especially
t-TUCB.
Translational
studies
human
functions
warranted.
Язык: Английский
Inkretine als Grundlage der Adipositastherapie
Deleted Journal,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 10, 2025
Obesity
represents
an
immense
challenge
for
patients
and
physicians
due
to
its
numerous
comorbidities
complications.
For
a
long
time,
safe
effective
pharmacological
treatment
remained
wishful
thinking.
Bariatric
surgery
was
considered
the
only
option
sustained
weight
loss;
however,
with
advent
of
incretin-based
treatment,
initially
introduced
as
highly
component
anti-diabetic
research
began
focus
on
complex
gastroenteropancreatic
endocrine
system,
including
central
hunger
satiety
regulation.
This
shift
driven
by
discovery
remarkable
side
effect:
placebo-controlled
reduction.
Subsequent
groundbreaking
developments
based
long-acting
peptides,
administration
which
could
be
reduced
from
twice
daily
in
earlier
forms
once
weekly,
now
enables
significant
reduction
over
20%,
tolerable
safety
profile.
article
provides
illustrative
overview
corresponding
associations
highlights
this
milestone
obesity
treatment.
Язык: Английский
Glucagon-like peptide-1 receptor agonists for major neurocognitive disorders
Journal of Neurology Neurosurgery & Psychiatry,
Год журнала:
2025,
Номер
unknown, С. jnnp - 335593
Опубликована: Апрель 10, 2025
Disease-modifying
treatments
for
major
neurocognitive
disorders,
including
Alzheimer’s
disease,
Parkinson’s
disease
and
other
cognitive
deficits,
are
among
the
main
unmet
needs
in
modern
medicine.
Glucagon-like
peptide-1
receptor
agonists
(GLP-1RAs),
currently
licensed
treatment
of
type
2
diabetes
mellitus
obesity,
offer
a
novel,
multilayered
mechanism
intervention
neurodegeneration
through
intermediate,
aetiology-agnostic
pathways,
likely
involving
metabolic,
inflammatory
several
relevant
neurobiological
processes.
In
vitro
animal
studies
have
revealed
promising
signals
neuroprotection,
with
preliminary
supportive
evidence
emerging
from
recent
pharmacoepidemiological
investigations
clinical
trials.
this
article,
we
comprehensively
review
that
investigate
impact
GLP-1RAs
on
various
aetiologies
impairment
dementia
syndromes.
Focusing
human
studies,
highlight
how
brain
energy
homeostasis,
neurogenesis,
synaptic
functioning,
neuroinflammation
cellular
stress
responses,
pathological
protein
aggregates,
proteostasis,
cerebrovascular
system
blood-brain
barrier
dynamics
may
underlie
GLP-1RA
putative
neuroprotective
effects.
We
then
report
appraise
observational
investigations,
trials
pooled
analyses.
Finally,
discuss
current
challenges
perspectives
ahead
research
implementation
care
people
their
individual
penetrance
potential,
need
response
biomarkers
stage-based
indications,
possible
non-specific
effects
health,
profile
terms
adverse
events
unwanted
effects,
lack
long-term
data
efficacy
safety,
issues
surrounding
cost
availability
treatment.
Язык: Английский