Download Fat Metabolism during One Hours Exercise on High and Low Doses

95
Bbchemistry of Ewrciw
l3COZenrichment (from [ 1-13C]palmitate) and 14C0,
specific activity (SA) (from [1-14C] acetate) were
measured over the last 20 min to determine the
recovery of label from acetate and to calculate
plasma FFA oxidation rates. Acetate directly enters
the TCA cycle and, under the present experimental
conditions, is completely oxidized; thus, the label in
acetate that is retained in the body will reflect label
fixation via exchange reactions in the TCA cycle and
also via labeled COz fixation by other mechanisms.
Since at rest there is no net use of intracellular fatty
acids, tracer estimates of plasma FFA oxidation
should approximate total fatty acid oxidation, if the
correction is valid. The fractional recovery of label
from acetate was 0.5920.12 (mean+SE). Total fatty
acid oxidation, calculated from indirect calorimetry
(IC), was 3.35 +- 0.29 pmol. kg-'. m i d . Isotopically
determined plasma FFA oxidation rates were 1.96 +0.16 (pc0.05 vs IC), and 3.34 2 0.24 pmol. kg-'.
min-'@=NS vs IC) when 1.0 (i.e; no correction), or
0.59 (i.e; the "acetate correction") were used as
correction factors, respectively.
We have also performed experimentsduring
exercise of moderate intensity to determine the
effect of label fixation on estimations of plasma and
intracellular fatty acid oxidation. [ 1-I3C] Palmitate
and [ 1-'4C]acetate were infused intravenously in 5
healthy volunteers during 1 hour of cycling at
402 10% V0,max. The fractional recovery of label
from acetate was 0.8620.03. Total fatty acid
oxidation, calculated from indirect calorimetry, was
10.721.9 pmol. kg-'. m i d . Without correction,
plasma FFA oxidation was 6.720.6pmol. kg". m i d ,
and intracellular fatty acid oxidation was 4.020.5
pmol. kg-'. m i d . When the "acetate correction
factor" (i.e; 0.86) was applied, plasma FFA oxidation
was 15% higher and intracellular fatty acid oxidation
was 25% lower. We conclude that the "acetate
correction factor" enables accurate determination of
plasma FFA oxidation using tracer techniques, and
failure to use this factor may result in a significant
overestimation of the oxidation of intramuscular
fatty acids during exercise.
drugs, change substrate metabolism during exercise'.
The effects of low and high doses of B, selective and
non selective drugs on exercise metabolism were
examined.
20 healthy subjects, male and female,
walked on a treadmill at 50% of their VOz max for
1 hr, 5 times, on each treatment, in random order:
Placebo
Metoprolol(50 mg)
(MP 50)
Metoprolol(100 mg)
(MP 100)
Propranolol(40 mg)
(Pr 40)
Propranolol(80 mg)
(Pr 80)
Energy expenditure and fat oxidation were
assessed by indirect calorimetry. Blood was drawn
via an intravenous cannula, and plasma assayed for
free fatty acids (FFA), glycerol, glucose, lactate and
ammonia.
All beta blockers reduced fat oxidation to
some degree (Table). Decreased fat oxidation
correlated with increased plasma ammonia (8 =
.924, p = .009), and increased leg effort (8 = .964,
p = .003). At 60 min of exercise, plasma ammonia
was significantlyhigher than placebo on Pr 40, Pr 80
and Mp 100 (p = <.0001 for all). On Mp 50, there
was no difference from placebo (p = .3274).
Increased plasma ammonia correlated with increased
leg effort (r2 = . 9 4 , p = .OW).
Plasma free fatty acids were lower than
placebo on all drug treatments (p = <.0001 ), but
there were no differences between drugs. It is
proposed that the additional inhibition of fat
oxidation with a non selective drug occurs in
intramuscular B, mediated lipolysis, rather than in
adipose lipolysis, as blockade of adipose FFA
release was maximal for all drug treatments.
Supported by NIH- grants DK-34817.and DK-46017. Labros S.
Sidossis was an "Alexander S. Onassis" Foundation Scholar.
Propranold
4Omg
106*'*
PmpnnokA
80mg
FAT METABOLISM DURING ONE
HOURS EXERCISE ON HIGH AND LOW
DOSES O F PROPRANOLOL,
METOPROLOL OR PLACEBO
A Head, S Maxwell, MJ Kendall. C.I.U., Q.E.
Hospital, Birmingham.
151
Beta-blockers, particularly non B, selective
Table: Heart rate (HR), fat oxidation and plasma free fatty acids
(FFA) during ihr treadmill exercise at 50% V
O
,
(N=20)
IFat
FFA
Treatment HR
s.d.
at Wmin
s.d
(pmoVl)
Placcbo
11
42.7
11.6
300.5
10
38.79
14.1
117.8"'
7
36.3..
13.7
152.88g' 169.6
8
31.2.V
9.3
134.1*** 114.4
8
29.5*'*##
10.9
111.0*** 84.0
134
s.d
217.4
Metropmld
Mmg
103***
Mctmpmld
100mg
97***
97***
79.5
Significantly lower than placebo +p= <.05, **p= <.01, '**p= C.001
Significantly lower than metoprolol 'p= <.O1,"p= <.OO1.
1. Clerow J, Leenen FH: Effects of beta blockade
on muscle metabolism during prolonged exercise. A
short review.Am J Hypertension 19881; 290s-294s