3
a
"Metabolic
flexibility"
is
the
ability
of
an
organ
to
adapt
to
changes
in
energy
demand
and
fuel
management
f
rom
fasting
to
fed
states.
Hyperglycemia
and
hyperinsulinemia
with
potential
worsening
of
obesity
and
adiposopathy.
Positive
caloric
balance
and
adiposopathy
•
Energy
overflow
•
Increased
circulating
•
Free
fatty
acids
(FFAs)
•
Immunopathies
•
Endocrinopathies
Liver
Dysfunction
•
FFA
influx
and
fatty
liver
•
Metabolic
inflexibility
a
•
Hepatic
dysfunction
•
Insulin
resistance
•
Often
first
major
post-AT
organ
with
dysfunction
leading
to
metabolic
disease
Muscle
Dysfunction
•
FFA
influx
and
intramyocellular
lipids
(e.g.,
ceramides
and
diacylglycerol)
•
Metabolic
inflexibility
a
•
Insulin
resistance
(skeletal
muscle
responsible
for
up
to
90%
of
glucose
disposal;
often
first
major
post-adipose
organ
causing
metabolic
disease)
•
Hyperinsulinemia
•
Pancreatic
beta
cell
dysfunction
•
High
blood
sugar
•
High
blood
pressure
•
Dyslipidemia
•
Heart
disease
•
Cancer
Simplified
Mechanism
of
Obesity,
Insulin
Resistance,
and
Metabolic
Disease
