The effects of hypergravity (centrifugation) on body composition were investigated. Hypogravitational and hypergravitational aspects were reflected in the research effort. A list of publications is provided

Pitts, G. C.

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	 (HAS A-CR-175393) RAT BODY SIZE, COMPOSITION 	 N84-20126
AND GRUWTH AT HTPO- AND HYPERGRAVITY Fioal
Report ( Virginia Univ.) 8 p HC A02/MF A01
	CSCL Q6C	 Unclas
G3/51 18676
FINAL REPORT
NSG - 2225
A Research Grant From NASA
'S	 to
Ab
^^ a U---ersity of Virginia
O
for the period
April 1977 to July 1983
titled
Rat body size, composition and growth at hypo- and hypergravity
by
X/m, . q"e,
Grover C. Pitts
Department of Physiology
School of Medicine
University of Virginia
Charlottesville, VA 22908
July 15, 1983
1INTRODUCTION
At the time of the initiation of this grant (1977) the Division of Life
Sciences of NASA waa deeply concerned with testing the possibility that
hypokinesia might be a useful simulation of weightlessness in the rat.
Consequently the original title of this grant was "Mammalian body size,
composition and growth as influenced by hypokinesia" and approximately the
first year was devoted to an evaluation of the influence on body composition
of cage restraint as a form of hypokinesia. Some of the results of these
early efforts are included in Publication No. 11. We soon realized that
hypokinesia was a poor simulator of weightlessness in its effects on rat body
composition. With the approval of our NASA monitor and funding officials we
returned to the other respect of our proposal, the effects of hypergr&7ity
(centrifugation) on body composition.
In 1979 we were given an opportunity to study the effects on rat body
composition of weightlessness on a Soviet Cosmos mission. This study was
funded primarily by Contract NAS2 - 10195 but much of the processing of data
and write-up was supported by the present research grant. The present title
of the grant reflects both the hypogravitational and hypergravitational
aspects of the total research effort.
ACHIEVEMENTS
Note on cost effectiveness: Many federal programs are evaluated as yield per
dollar invested. This principal is not directly applicable to scientific
research since while the quantitative yield (number of papers, or journal
pages) is readily apparent, the quality of the yield usually becomes apparent
+fir
2only in retrospect at a later date.
	 However, the present grant is an extreme
case.	 The four years of funding (1977 to 1981 with no-cost extensions to
1983) totaled $101,000 and each year 35% was deducted as overhead.
	 This left
$16,412 for each of the four grant years available to the investigator.
	 While
this level of funding is appropriate for library research, by careful
husbandry and "scrounging" we were able to do laboratory research involving
certrifugation at a distant site.
	 Dollar efficiency is rarely an important
t
consideration in scientific research, but certainly in this case NASA received
a bargain.
i
Publications:
1.	 Pitts, Grover C. Physiological regulation of body energy storage.
Metabolism 27:469-478, 1978.
	 This is a "spin-off" paper in basic science,
i
only indirectly related to gravitational physiology.
	 It presents evidence F
that while the energy storage in adipose tissue appears to be regulated, the,. :t
^:	 I
regulatory mechanism provides scope for wide variations in the midrange.
2. Pitts, G.C. and J. Oyama. Rat growth during chronic centrifugation. Life
Sci. Space Res. 17 : 225-229, 1979. This study revealed that rats chronically
centrifuged at 4.2g starting at the age of weaning followed a lower growth
curve and achieved a smaller mature mass than controls at terrestrial gravity.
Most body components contributed proportionately to this difference in total
mass. All changes in the centrifuged group returned to control levels during z
57 days of retirement to terrestrial gravity.
3. Donald, Patillo, Grover C. Pitts and Stephen L. Pohl. Body weight and
composition in laboratory rats: effects of diets with high or low protein
concentrations. Science 211 : 185-186, 1981. This is another spin-off paper in
basic science only indirectly related to gravitational physiology. Rats on
III
e	
^
3high levels of dietary protein deposited more body fat than those on lower
levels.
4. Pace, Nello, D.F. Rahlmann, A.H. Smith and Grover C. Pitts. Effects of
the Cosmos 1129 Soviet paste diet on body composition in the growing rat.
Environmental Physiology Laboratory, University of Caifornia, Berkeley.
Report EPL 81-1. In a study of the effects on rat growth of the Soviet paste
diet Grindeland, Yang, Madsen and Reil of Ames Research Center reported that
the diet did not support optimal growth and suggested the desirability of body
composition studies. The present authors volunteered to do such studies and
make the results available to all of the American investigators planning rat
studies on Cosmos 1129. This report is the result of that study. We foun,-
that the group on the Soviet diet was 10% lower in total body mess, 13% higher
in resting metabolic rate, 50% higher in body fat and 16% lower in fat-free
body mass. It was difficult to establish the dietary factors responsible but
some possibilities were discussed.
5. Pitts, G.C. and J. Oyama. Response of rat body composition to 	
E-
simultaneous exercise and centrifugation at 3.148. Pflugers Archiv - European
Journal of Physiology 391 Supplement:R66, 1981. This is a separately printed
abstract of the paper which follows.
6. Pitts, G.C. and J. Oyama. Response of rat body composition to
simultaneous exercise and centrifugation at 3.14g. The Physiologist. 24
Supplement:S95-S96, 1981. Muscles contracting against increased loads may 	 r
show increases in mass (hypertrophy). Nevertheless, rats subjected to such 	 .!
load increases by centrifugation show a decrease in muscle mass. Since rats	 +
may protect themselves against exposure to such increased loads by lying down 	
Y
most of the time, we decided to look for the load effect in animals
volitionally running in a runniing wheel while centrifuged. Controls were
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4severely restrained by small cages during centrifugation. The two groups were
statistically identical. If the load effect were present but concealed by
opposing factors, our statistical treatment should have revealed it. Probably
there is no load factor operating in the centrifuged rat.
7. Pnce, Bello, Grover C. Pitts, Arthur H. Smith, D.F. Rahlmann, Arkad, i S.
Ushakov and Tamara A. Smirnova. Body composition data from the rat subjects
of Cosmos 1129 Experiment K-316. Environmental Physiology Laboratory,
University of California, Berkeley. Report EPL 82-1, 1982. In this report
full results of the body composition analyses on rats used in Cosmos 1129,
Experiment K-316 are presented in complete detail whic;i is not permitted in
the physiological press.
8. Pitts, Grover C. Effects of chronic acceleration on body composition.
The Physiologist, 25 Supplement:S13-S16, 1982. This is an invited paper for
the Symposium on Gravitational Physiology at the Fourth Annual Meeting of the
IUPS Commission on Gravitational Physiology. It is a short review of my
contributions to the effects on rat body composition of centrifugation and
weightlessness.
9. Pitts, G.C., A.S. Ushakov, N. Pace, A.H. Smith, D.F. Rahlmann, and T.A.
Smirnova. Effects of weightlessness on body composition in the rat. Am. J.
Physiol. 244 (Regulatory Integrative Comp. Physiol. 13):R332-R337, 1983. This
is the definitive report for the physiological community of our results on
body composition of rats exposed to 18.5 days of weightlessness on Cosmos
1129. The results included 1) a reduced fraction of total body water, 2) a
net shift of body water from skin to viscera, 3) a marked diminution in
fraction of extracellular water in the fat-free body, 4) a marked reduction in
fraction of bone mineral, 5) no change in the quantity of stored fat or
adrenal masses, and
	
a net increase in total muscle mass.
1	 .
5
10. Pitts, Grover C. Distribution of fluids in the body of the centrifuged
rat. The Physiologist. In press. This is to be presented at the Fifth
Annual Meeting of the IUPS Commission on Gravitational Physiology, Moscow,
USSR. It demonstrates that centrifugation throughout the period of rapid
growth causes some changes in the masses of fluids and solids in the rat.
However, all such changes are reversible upon retiring from the centrifuge to
terrestrial gravity.
11. Pitts, Grover C. Body composition in the rat: interactions of exercise,
age and sex. Am. J. Physiol. Submitted for publication. This is a
contribution to basic science indirectly related to gravitational physiology.
It is demonstrated that an exercise regimen initiated at 7 weeks of age or
younger results in a change in the fat-free body mass -:n either sex. But the
fat-free body mass increases in females and decreases in males. Exercise
initiated at 11 weeks of age or older has no effect on the fat-free body mass.
12. Pitts, Grover C. Muscle and bone masses as a function of body size in
the rat. Manuscript in preparation. With increasing body size muscle mass
changes much more rapidly than does skeleton mass.
13. Pitts, Grover C. A theory of the regulation of catch-up growth.
Manuscript in preparation. Some rather complex mechanisms for the control of
catch-up growth have been proposed. This manuscript will propose a much
simpler mechanism based on whether or not the perturbing mechanism causes loss
of cells.
Significant contributions:
1. In the rat eating a balanced diet ad libitum it is very difficult to
perturb the fat-free body mass. Indeed centrifugation is the only factor we
have found which will do so in the adult. However, all of these body
composition effects of centrifugation are reversible upon retirement to
6terrestrial gravity, oven in rats which have been centrifuged for
approximately one year starting at weaning (Publ. 2, 8, 10 and earlier
publications).
2. Contrary to expectations total .vans of skeletal muscle in the rat is
reduced as a consequence of chronic acceleration (2, 8 and earlier
publications).
3. Contrary to expectations total mass of skeletal muscle in the rat appears
to be increased as a result of weightlessness. The evidence is good but this
needs to be corroborated. (7, 8 and 9).
4. It is generally acknowledged that overload (as in centrifugation) will
cause skeletal muscles to increase in mass (hypertrophy). Contribution number
2 shows that we observed the reverse. Our efforts to show that the
hypertrophic response to overload was actually present but concealed by
opposing influences were to no avail. Apparently centrifugation does not
result in an overload response. (6).
5. While masses of many body components change as a result of centrifugation
during growth, the only change associated with centrifugation per se is the
gain in mass of fat-free skin (2, 8 and 10).
6. The effects of gravity on mammals are a function of body size and a vriori
there was reason to believe that rats were too small to respond to the - lg
in weightlessness. We showed that rats did respond to weightlessness. The
changes seen included: a reduction in total body water, shifts in fluid
compartments, a reduction in bone mineral and an increase in total skeletal
musculature (7 and 9).
7. Our analysis of the changes in body fat content in mammals suggests that
the regulation of body fat content is such as to protect the body from very
low and very high values but allows considerable variation throughout the
7midrange (Publication 1).
8. Rats on diets containing high levels of protein deposit more fat than
those on isocaloric diets containing low levels of protein. Tais is contrary
to generally accepted nutritional beliefs. (Publication 3).
9. Mass of the fat-free body compartment in the rat may be altered by
exercise and diet in animals 7 weeks of age and younger. At 11 weeks of age
and older the regulatory mechanism protecting the fat-free body mass against
perturbation has apparently matured and fat-free body mass remains constant in
the face of such perturbations. (Publication 11).
10. There is a striking sex difference in the response of young rate (7 weeks
of age and younger) to a daily exercise regimen. In exercising males the
fat-free body compartment grows more slowly than in unexercised controls and
in females, more rapidly. In both sexes exercise decreases body fatness.	 R
(Publication 11).	 gl
WPENDIX
Reprints of publications 1 through 9 attached hereto.


Rat body size, composition and growth at hypo- and hypergravity

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