Cell Metabolism,
Journal Year:
2024,
Volume and Issue:
36(6), P. 1184 - 1203
Published: April 1, 2024
Futile
cycles
are
biological
phenomena
where
two
opposing
biochemical
reactions
run
simultaneously,
resulting
in
a
net
energy
loss
without
appreciable
productivity.
Such
state
was
presumed
to
be
aberration
and
thus
deemed
an
energy-wasting
"futile"
cycle.
However,
multiple
pieces
of
evidence
suggest
that
utilities
emerge
from
futile
cycles.
A
few
established
functions
control
metabolic
sensitivity,
modulate
homeostasis,
drive
adaptive
thermogenesis.
Yet,
the
physiological
regulation,
implication,
pathological
relevance
most
remain
poorly
studied.
In
this
review,
we
highlight
abundance
versatility
propose
classification
scheme.
We
further
discuss
energetic
implications
various
their
impact
on
basal
rate,
bona
fide
tentative
pathophysiological
implications,
putative
drug
interactions.
Journal of Hepatology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 1, 2025
The
liver
acts
as
a
central
metabolic
hub,
integrating
signals
from
the
gastrointestinal
tract
and
adipose
tissue
to
regulate
carbohydrate,
lipid,
amino
acid
metabolism.
Gut-derived
metabolites,
such
acetate
ethanol
non-esterified
fatty
acids
white
(WAT),
influence
hepatic
processes,
which
rely
on
mitochondrial
function
maintain
systemic
energy
balance.
Metabolic
dysregulation
obesity,
insulin
resistance,
type
2
diabetes
disrupt
these
pathways,
leading
dysfunction-associated
steatotic
disease
(MASLD)
steatohepatitis
(MASH).
This
review
explores
fluxes
within
gut-adipose
tissue-liver
axis,
focusing
pivotal
role
of
de
novo
lipogenesis
(DNL),
dietary
substrates
like
glucose
fructose,
changes
in
during
MASLD
progression.
It
highlights
contributions
resistance
impaired
dynamics
lipid
accumulation.
Further
understanding
how
interplay
between
substrate
flux
gastro-intestinal
integrates
with
intersects
structural
functional
alterations
mitochondria
will
be
important
identify
novel
therapeutic
targets
advance
treatment
MASH.
BioEssays,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 19, 2025
ABSTRACT
Adipose
tissue
(AT)
inflammation,
a
hallmark
of
the
metabolic
syndrome,
is
triggered
by
overburdened
adipocytes
sending
out
immune
cell
recruitment
signals
during
obesity
development.
An
AT
landscape
persistent
throughout
weight
loss
and
regain
constitutes
an
immune‐obesogenic
memory
that
hinders
long‐term
management.
Lipid‐associated
macrophages
(LAMs)
are
emerging
as
major
players
in
diseased,
inflamed
tissues
may
be
key
contributors
to
obesogenic
AT.
Our
previous
study
found
LAM
abundance
increases
with
via
intermittent
fasting
(IF)
obese
mice,
which
driven
adipocyte
p53
signalling.
However,
specific
causing
accumulation
under
IF
remain
unknown.
In
this
piece,
we
hypothesise
on
range
adipocyte‐secreted
can
harbor
immune‐attractive
features
upon
fasting/refeeding
cycles.
We
highlight
possible
mechanisms
including
death
signalling,
matrikines,
other
damage‐associated
molecular
patterns
(DAMPs),
well
adipo(‐cyto)kines,
lipid
mediators,
metabolites,
extracellular
vesicles,
epigenetic
rewiring.
Finally,
consider
how
advances
gleaned
from
preclinical
models
might
translatable
management
humans.
Thus,
provide
vantage
points
driving
monocyte
recruitment,
polarisation
towards
LAMs,
retention,
harness
therapeutic
potential
modulating
levels
impacting
disease.
Proceedings of the National Academy of Sciences,
Journal Year:
2025,
Volume and Issue:
122(8)
Published: Feb. 20, 2025
While
it
is
known
that
endocannabinoids
(eCB)
modulate
multiple
neuronal
functions,
the
molecular
mechanism
governing
their
release
and
transport
remains
elusive.
Here,
we
propose
an
"on-demand
release"
model,
wherein
formation
of
microvesicles,
a
specific
group
extracellular
vesicles
(EVs)
containing
eCB,
2-arachidonoylglycerol
(2-AG),
important
step.
A
coculture
model
system
combines
reporter
cell
line
expressing
fluorescent
eCB
sensor,
G
protein-coupled
receptor-based
(GRAB)eCB2.0,
cells
revealed
neurons
EVs
2-AG,
but
not
anandamide,
in
stimulus-dependent
process
regulated
by
protein
kinase
C,
Diacylglycerol
lipase,
Adenosinediphosphate
(ADP)
ribosylation
factor
6
(Arf6),
which
was
sensitive
to
inhibitors
facilitated
diffusion.
vesicle
contained
approximately
2,000
2-AG
molecules.
Accordingly,
hippocampal
eCB-mediated
synaptic
plasticity
modulated
Arf6
inhibitors.
The
supported
mathematical
analysis,
offers
cohesive
framework
for
understanding
trafficking
at
level
suggests
microvesicles
carrying
signaling
lipids
membrane
regulate
functions
parallel
canonical
vesicles.
Advanced Materials,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 2, 2025
Higher
and
richer
nutrient
requirements
are
typical
features
that
distinguish
tumor
cells
from
AU:
cells,
ensuring
adequate
substrates
energy
sources
for
cell
proliferation
migration.
Therefore,
deprivation
strategies
based
on
targeted
technologies
can
induce
impaired
viability
in
which
more
sensitive
than
normal
cells.
In
this
review,
nutrients
required
by
related
metabolic
pathways
introduced,
anti-tumor
developed
to
target
described.
addition
the
nutritional
characteristics
of
other
microenvironment
(including
macrophages,
neutrophils,
natural
killer
T
cancer-associated
fibroblasts)
new
also
summarized.
conclusion,
recent
advances
targeting
blockade
reviewed,
challenges
prospects
these
discussed,
theoretical
significance
optimizing
clinical
application
nutrition
strategies.
Lipids,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 31, 2025
Abstract
Poor
sleep
is
linked
to
an
increased
risk
of
metabolic,
cardiovascular,
psychiatric,
and
neurodegenerative
diseases,
highlighting
its
emergence
as
a
public
health
concern.
Previous
studies
demonstrated
the
harmful
effects
trans
fatty
acids
(TFAs)
on
human
health.
However,
association
between
TFAs
outcomes
still
not
well‐established.
The
current
study
aimed
investigate
relationship
plasma
elaidic
acid,
major
TFA,
complaints.
participants
from
US
National
Health
Nutrition
Examination
Survey
(NHANES)
(2009–2010)
were
included.
concentration
acid
(18:1n‐9t)
was
determined
using
gas
chromatography/mass
spectrometry
(GC/MS)
method.
outcome
defined
based
following
questionnaire:
“Ever
told
doctor
had
trouble
sleeping?”
by
have
disorder?”.
Participants
classified
having
complaints
if
they
ever
or
been
about
sleeping.
investigated
multivariable
logistic
regressions,
restricted
cubic
spline
(RCS),
subgroup
analysis.
A
total
2068
included,
561
whom
suffered
(RCS)
regression
analysis
revealed
nonlinear
(inverted
L‐shaped)
level
(
p
=
0.044),
with
inflection
point
9.598
μmol/L.
In
group
low
(≤9.598
μmol/L),
there
positive
prevalence
(OR
1.28;
95%
CI:
1.06–1.54,
0.01).
When
more
than
μmol/L,
correlation
statistically
significant.
Results
robust
when
analyses
stratified
sex,
age,
race,
marital
status,
education
level,
family
income,
BMI
(all
for
interaction
>0.05).
results
in
adults
≤9.598
μmol.
Given
that
TFA
content
has
considerably
declined
recent
years,
detrimental
impact
quality
deserves
attention.
Aging Cell,
Journal Year:
2024,
Volume and Issue:
23(12)
Published: Aug. 23, 2024
Abstract
Adipose
thermogenesis
has
been
actively
investigated
as
a
therapeutic
target
for
improving
metabolic
dysfunction
in
obesity.
However,
its
applicability
to
middle‐aged
and
older
populations,
which
bear
the
highest
obesity
prevalence
United
States
(approximately
40%),
remains
uncertain
due
age‐related
decline
thermogenic
responses.
In
this
study,
we
effects
of
chronic
stimulation
using
β3‐adrenergic
(AR)
agonist
CL316,243
(CL)
on
systemic
metabolism
adipose
function
aged
(18‐month‐old)
C57BL/6JN
mice.
Sustained
β3‐AR
treatment
resulted
reduced
fat
mass,
increased
energy
expenditure,
fatty
acid
oxidation
mitochondrial
activity
depots,
improved
glucose
homeostasis,
favorable
adipokine
profile.
At
cellular
level,
CL
uncoupling
protein
1
(UCP1)‐dependent
brown
tissue
(BAT).
white
(WAT)
glycerol
lipid
de
novo
lipogenesis
(DNL)
turnover
suggesting
activation
futile
substrate
cycle
lipolysis
reesterification
UCP1‐independent
manner.
Increased
was
also
associated
with
simultaneous
upregulation
proteins
involved
metabolism,
oxidation,
WAT.
Further,
dose‐dependent
impact
inflammation
observed,
particularly
subcutaneous
WAT,
potential
mismatch
between
supply
oxidation.
These
findings
indicate
that
activates
distinct
mechanisms
increase
expenditure
BAT
WAT
improve
Considering
people
lose
aging,
cycling
presents
novel
strategy
dysfunction.
