Beruflich Dokumente
Kultur Dokumente
Kevin JAcheson, Jean-Pierre Flail, PhD; PhD; Yves Schutz, PhD; Thierry and Eric J#{233}quier, MD The metabolic balance excesses ofcarbohydrate.
MJ [1994 65 kcal]
during
PhD;
Bessard,
MD;
Krishna
Anantharaman,
ABSTRACF
method was performed on three men to investigate Glycogen stores, which first depleted were by diet (3
decreasing to 5.70 1.03 MJ [1361 247 kcal], 15%
protein,
75%
fat,
10% carbohydrate)
and
exercise,
were
repleted
during
.
7 d carbohydrate
overfeeding (1 1% protein, 3% fat, and 86% carbohydrate) providing 15.2510 MJ 1 (3642 263 kcal) on the first day, increasing progressively to 20.64 1 .30 MJ (4930 3 1 1 kcal) on the last day of overfeeding. Glycogen depletion again was accomplished with 2 d of carbohydrate restriction (2.52 MJ/d [602 kcal/d], 85% protein, and 1 5% fat). Glycogen storage capacity in man is 15 g/kg bodyweight and can accommodate gain of -5#{174} before a g net lipid synthesis contributes to increasing body fat mass. When the glycogen stores are saturated, massive intakes ofcarbohydrate are disposed ofby high carbohydrate-oxidation rates and sub-
stantial
de novo
lipid
Am
synthesis
JClin
(1 50 g lipid/d
Nutr 1988;48:240-7.
using
-475
g CHO/d)
without
postabsorptive
hyperglycemia.
KEY rect WORDS calorimetry,
body
Carbohydrate composition
overfeeding,
glycogen stores,
de novo
lipid
synthesis,
mdi-
a liver weighing 1 .8 kg, one can estimate that .3 mol gjycosyl residues or almost 500 g of glycogen are stored It has long been known from studies involving carcass in the body. If the highest reported literature values (1, and organ analysis in animals that the composition of are extrapolated 3) to the whole body, then up to 4.3 mol the diet and its availability effect the organisms glycogen glycosyl residues or some 700 g of glycogen could be reserves. The work of Bergstrom et al (1) and Huitman stored in the body. and Nilsson (2) using muscle and liver biopsies provided Although it is known that this value can be increased direct measurements ofsuch changes in man. The high- markedly during glycogen loading, when muscle glycoest muscle glycogen levels were observed when glycogen gen levels can reach 2.4 g/lOO g wet muscle or more (1), stores are first depleted by sustained exercise followed by it is often believed that the glycogen stores are normally ingestion of a high-fat diet and then repleted by con-maintained within a relatively narrow range. However, sumption of a carbohydrate-rich diet, ie, the glycogen the capacity for storing large amounts dietary of carboloading technique (1). hydrate by conversion to glycogen is in fact considerable Skeletal muscles and liver are the principal sites for the (5-7). To assess the upper limit for glycogen storage in storage of glycogen in the body. Liver glycogen concen- man, we performed continuous metabolic balance studtrations vary with the diet with values in the range of 50500 mmol glycosyl residues/kg tissue in the postabsorpI From the Institute ofPhysiology, Faculty ofMedicine, University tive state (mean 270 mmol [44 g] glycosyl residues/kg Lausanne, Switzerland; the Nestl#{233} Research Center, Nesliver) (3). Liver glycogen varies appreciably during theofLausanne, tee Lausanne, Switzerland; and the Departday in relation to the patterns of eating and fasting (2). Ltd, Vers-chez-les-Blanc, ment of Biochemistry, University of Massachusetts, Medical Center, Glycogen concentrations in biopsy samples from the Worcester, MA. quadriceps femoris muscle were found to be in the range 2 Supported by the Nestl#{233} Switzerland. Co. of6O-l20 mmol glycosyl residues/kg with a mean of 85 3 Address reprint requests to KJ Acheson, Institute of Physiology, mmol (14 g) glycosyl residues/kg tissue (4). However, the University ofLausanne, Rue du Bugnon 7, CH-l005 Lausanne, Switglycogen concentration in skeletal muscle also depends zerland. upon the muscle group being investigated (4). For a 70- ReceivedJune 15, 1987. October 6, 1987. kg man with -40% ofhis weight as skeletal muscle and Accepted for publication Introduction 240
Am
JC/in
Nuir
l988;48:240-7.
Printed
in USA.
1988
American
Society forClinical
Nutrition
DISPOSAL massive
IN OVERFEEDING
241
ofcarbohydrates
and methods
were
ingested.
Subjects
Subjects
Three
healthy
swimmer
young at university
men, level,
and
sity
one of whom was a competition (21-22 y, 62-72 kg, 174-180 no family history ofdiabetes or obe-
The frozen sample was dried to constant weight to establish its water content. The residue was ground to a powder thatwas analyzed for nitrogen (10), extractable fat by the Soxlet method (1 1), and ash contents. Dietary protein was taken 6.25 be to x total N and the carbohydrate content was calculated by difference (ie, dry weight [weight protein + fat + ash]). Much of the excess carbohydrate was provided by sugared fruitjuices ofknown uniform composition and energy content. in the 20% duplicate sample but were cm, These were not included
-
analyzed
separately;
their
energy
contents
were
found
to agree
any
medication,
participated in
this study. The subjects were each given a detailed account the protocol, which had previously been reviewed and accepted by the institutes ethical committee, before they gave their consent to participate. Protocol
with those indicated by the manufacturers. The energy ofthe fruit juices was added to the gross energy values high-carbohydrate diets.
expenditure
low-carbohydrate diet, physical activity was a pedometer (Pedoboy #10, Barigo Barometer Schweninger, FRG). Heart rate was monitored using a portable heart-rate monitoring instru2 d on
the
high-fat,
but
The experiment
3 d the subjects
lasted
consumed
14 consecutive
a restricted
days.
diet,
During
first the
high
in fat and
in carbohydrate, and followed an exercise program. through this period the subjects were admitted into a respiration chamber in which respiratory exchange measurements
ment
(HRM,
Difa,
Breda,
Holland).
The
subjects
performed
At
various types of physical activity, ie, running and swimming, during this period to deplete their muscle glycogen stores. were to be continued for 10 d. After 36 h in the chamber the 2, each subject was admitted into an open-circuit diet was changed to a high-carbohydrate, low-fat diet that was the end ofday calorimeter chamber (12) where energy expenditure ingested for the following 7 d. During the last 2 d while still in indirect
the chamber,
the subjects
received
limited
amounts
of a high- was
measured
continuously
for the
next
10 d. Resting
meta-
with a ventilatedprotein diet (protein-sparing modified-fast [PSMF], 2.5 MJ bolic rate was measured for 1 h each morning hood system within the chamber (12). Each day the subjects or 600 kcal) essentially devoid of carbohydrate. The subjects for two 30-mm periods (beginning 1 at 30 and 1 1730) then left the respiration chamber but continued to consume walked (Quinton Inst Co. Seattle, WA) at 2 mph (3.22 the high-fat, low-carbohydrate diet restricted in amounts for a on a treadmill km/h), 5% slope in the morning and 2 mph (3.22 km/h), 10% further 2 d. slope in the afternoon. During the remainder ofthe day, spontaneous physical activity was allowed within the confines imEnergy intake posed by the chamber but strenuous physical exertion not was The diets were prepared by trained dieticians at the Institute permitted. of Physiology. The restricted high-fat, low-carbohydrate diet The subjects were allowed to leave the chambertwice a day consumed on days 1-3 and 1 3-14 provided --6.70 MJ (1600 for 30 mm after the resting metabolic rate measurements in kcal) composed of 1 5% protein, 75% fat, and 10% carbohythe morningand again in the afternoon at 1630 during which drate. During the overfeeding period (days 4-10 inclusive) the time the calibrations of the analyzers were verified and other high-carbohydrate, low-fat diet provided 1 5 MJ (3600 kcal, measurements were performed, eg, body weight, urine colleccomposed of 1 1% protein, 3% fat, and 86% carbohydrate) on tion, etc. day 4. Energy intake was then increased progressively each day while the composition was kept constant to provide 6.28 MJ Nutrient balances (1500 kcal) in excess ofthe previous days energy expenditure, were collected from day until 1 several days after the which was measured in the respiration chamber (8). By day 10 Stools test. At each change in the diet the subject consumed 1 g carthe energy intake had thus increased to -21 Mi(5000 kcal). Stools were weighed, frozen, freeze For the next (and last) 2 d in the respiration chamber, the sub- mine red as afecal marker. for N, fat, and ash, and carbohydrate was jects consumed a high-protein, low-calorie diet (PSMF, --2.5 dried, and analyzed by difference as described above. MJ or 600 kcal). The diet was then changed to the same re- calculated nutrient and metabolizable energy instricted high-fat, low-carbohydrate diet eaten on days 1-3 for Twenty-four-hour from the food tables (9). The 24-h gross the last 2 d ofthe experiment spent outside the chamber. Each takes were calculated energy intake was also determined on the basis of the direct food item consumed wasweighed to the nearest gram with a analysis of the 20% dried duplicate sample and corrected for Mettler PlO balance (Mettler, Greifensee, Switzerland) and its losses in the stool collections between the appearance intake was corrected for any residue left on the plate. Energy nutrients intake and dietary composition were calculated from food taofthe fecal markers. Urine was collected during the day (14 h) and the night (10 bles (9) with a desk-top computer (HP 9830, Hewlett Packard was tested for glucose (Gluketur-Test, Boehringer (Schweiz) AG, Schlieren, Switzerland). The factors 16.74, h) and 37.67, and 16.74 kJ/g (4, and 4 kcal) were used to calculate 9, Mannheim Gmbh, Mannheim, FRG) and total N was ana--
oxidation was calculated by summing energy contents ofprotein, fat, and carbohy- lyzed (10). Daily protein Twenty percent, by weight, of each food the urinary N excretions during the day and the night and mulitem (except for the sugared fruit juices) ere set aside and w tiplying this value by 6.25. Twenty-four-hour carbohydrate were calculated according to classical formupooled. At the end of each 24-h period, the pooled samples and fat oxidations were homogenized. An aliquot was immediately freeze dried las (13) from the nonprotein respiratory quotient. (Virtis automatic freeze-drier, Gardiner, NY) and the remainFrom a knowledge ofthe composition ofenergy entering the body, that oxidized, and that leaving the body in urine and feder was frozen and stored at -20 #{176}C.
242 TABLE
Bodyweight 1 changes
ACHESON
ET AL
Subject
Age
y
Height day 1
cm 180 175 173.5 176.2
Start
fat
Start
Start
PSMF
13
End PSMF
day kg 71.5 69.6 61.7 67.6 15 End kg 71.9 68.8 61.4 67.4 test
,
day kg
2
3
22 21 21 21.3
I
SD
S
3.4 low-carbohydrate
4.6 low-fat
5.4
ces (hair
and
cutaneous
losses
daily the
were
assumed
to be negligible),
drate
diet,
the
increase
over
the
preceding
days
energy
Blood
variables
Blood samples were at the beginning ofand periment. They were free fatty acids (16) on and blood urea N (19). phoresis (Readysystem AG, Bad-Zurzack, thyroid hormone concentrations were radioimmunoassay ARIA II (Becton burg, NY).
intake rose to 0.95 MJ (227 kcal). This pattern was slightly different when intake was based on the data obtamed by direct analysis, where on the fifth day of overfeeding (day 8) the additional energy was 1.94 MJ taken in the postabsorptive fasting state (464 kcal) and fell to 0 on the last day overfeeding of (day at regular intervals throughout the cx10). The food tables overestimated protein and carbohyanalyzed for glucose (14), insulin (15), drate intakes during each ofthe different diets except for the Dole extract (17), triglycerides (18), the 2 d on the low-energy, high-protein (PSMF) diet Lipoproteins were separated by electroSwitzerland)
analyzed
and Orange-
(days
1 1 and
12).
The
tables
overestimated
fat
intake
by automated
Dickinson,
during the low-energy high-fat, low-carbohydrate but considerably underestimated it during the bohydrate, low-fat diet by -40-80 g/d (670-1339
160-320 kcal/d).
diets high-carkJ/d;
The substrate balances calculated from substrates entering (direct analysis) and leaving the body are presented in Table 3. With the onset of carbohydrate Mean body weight decreased by 0.8 1.4 kg during there was a dramatic increase in carbohythe 3 d on the restricted, high-fat, low-carbohydrate diet overfeeding, drate oxidation (Fig 2) from 40 g/d (day 74 3) to 398 (Table 1). After the 7 d ofoverfeeding the high-carbohy 87 g/d (day 4). Thereafter carbohydrate utilization (ie, drate, low-fat diet (day 10), body weight had increased and that used for de novo lipid synthesis) inby 4.6 1 .3 kg (ie,5.6, 4.9, and 3.2 kg). During the 2 d oxidation creased progressively in response to the increase in caron the restricted high-protein, low-energy diet (600 kcal/ bohydrate ingestion, attaining 1010 37 g/d on the last d) 4.4 0.9 kg were lost. Two days later, ody b weights day of overfeeding. Concomitant with increase the in were the same as at the start of the overfeeding phase of utilization therewas a rapid suppression of the experiment (ie, 7 1 .3 and 7 1 .9, 68.6 and 68.8, 62.3carbohydrate lipid oxidation. and 61 .4 kg, respectively). After an initial decrease in protein oxidation at the beEnergy and nutrient intake ginning of carbohydrate overfeeding (from 104 12 to 82 7 g/d from day 4 to day 5), protein oxidation reThe composition ofthe diets over the l4-d experiment maimed relatively constant until the last 2 d of overfeedare presented in Table 2. From the ratio metabolizable of it increased in proportion with the protein in energy obtained from direct analysis and food tables, iting when the diet so that a positive N balance was maintained at can be seen that the food tables tended to overestimate g N during the last 5 d of overfeeding. energy intake with the high-fat, low-carbohydrate diet 3.8 As the diet passed from a hypocaloric high-fat, lowand underestimate during the high-carbohydrate, low-fat carbohydrate to a hypercaloric high-carbohydrate, lowoverfeeding and the high-protein low-energy diets. there was not only a large increase in When the high-carbohydrate, low-fat diet was initi- fat composition, oxidation but also in glycogen storage (339 ated, it was necessary to increase the energy intake by 8.8 carbohydrate each successive day the amount of carboMi (2100 kcal, food table data) to obtain a positive en- 82 g/d). With hydrate that was stored decreased even though the erg)1 balance of6.28 MJ (1 500 kcal) during first 24-h the amount that was ingested increased (Fig 2). After 4 d of period of overfeeding. On the second day an increase of overfeeding, the glycogen stores had become saturated 1 .54 MJ (370 kcal, food tables) was necessary to mainthat they had increased by -770 thin the same positive energy balance, the increment de- and it was calculated g. carbohydrate balance was maintained near creasing gradually to 0.42 MJ/d (100 kcal/d) over the Thereafter equilibrium. When the diet as devoid w of carbohydrate next 3 d (Fig 1). During the last 2 d ofthe high-carbohyResults
CARBOHYDRATE TABLE
Daily
DISPOSAL
IN OVERFEEDING
243
2
composition ofthe diet calculated by direct analysis and from food
(n = tables
3, 1
SD)
Nutrients Ingested
Day
excreted
direct
in eces from f
Available CHO g 139 129 2417 2013 2017 188 225 146 73 54 101 101 101 1610 Protein g 725 5016 4924 8218 934 1049 10214 11723 1226 12411 12610 12610 6420 6518 nu trients Fat g 1667 12848 1176 5619 9713 8124 7814 9423 10223 6923 102 112 11328 13521 from direct analysis5 CHO g 2918 4320 2816 73712 81378 84335 86858 93384 93245 98143 0 0 3314 497
nu trients
Fat g
Protein g
1 2 3 4 5 6 7 8 9 10 11 12 13 14
8612 636 759 10310 11616 12412 12513 13119 1312 13311 13610 13610 7722 7925
1728 13451 1283 6320 10411 8827 8516 9822 10522 7420 162 162 11829 14222
from
foodtablest CHO g 458 5912 472 83665 90089 94861 99468 98990 103874 107344 0 0 4314 6517
Metabolizable
Direct analysis/
food
energy
Day
Protein g
tables
%
1 2 3 4 5
6
7 8 9 10 11 12 13 14
S
798 708 694 1148 1245 1244 1273 12914 13810 14213 1124 1113 7519 7511
96 75 77 94
104 100
98 106 104 97 126 116 72 83
Nutrients
offood
and feces.
losses
+
t Available nutrients in foodusing Atwaters coefficients which allow for partial t From direct analysis, Metabolizable Energy Gross Energy (Fecal Energy
ineces (20). f
Urinary
Energy).
(days cipal
1 1 and 12), carbohydrate was still used as the prim- During the 6 d during which lipid synthesis exceeded energy substrate to the detriment of the glycogen fat oxidation, net de novo lipogenesis amounted to a tostores, which decreased by -7#{174}g during these 2 d. tal of -580 g. Because in addition to de novo lipogenesis The initial increase in the glycogen stores by 500 g some fat was provided in the diet (--85 g/d), the overall was accompanied by an increase in the mean 24-h non- fatgainwas-.l.l kg. protein respiratory quotient(Fig 3). The mean 24-h nonThe principal blood variables are presented in Table 4. The hypocaloric high-fat, low-carbohydrate diet caused protein respiratory quotient exceeded 1.00 (indicative of net de novo lipid synthesis) on day 2 of carbohydrate both plasma glucose and insulin concentrations to decrease and free fatty acids to increase. During carbohyoverfeeding; it continued to increase and reached a value of 1. 1 5 during the last 3 d of overfeeding when daily drate overfeeding plasma glucose rose initially but was at the control value obtained at the beginfat synthesis from glucose averaged 142 g/d. Even on day maintained 1 1 when no carbohydrate was present in the diet, the ning ofthe experiment by the rising plasma insulin conmean nonprotein respiratory quotient was still just centrations. Plasma triglycerides increased 10-fold dur> 1.00. ing carbohydrate overfeeding. This increase was realso
-
244
ACHESON
ET AL
1000
80o
Respiratory
Exchange
_I
600
0
>. I
g
C
C.)
400
200
FIG 2. Daily carbohydrate intake(and its disposal (oxidation, glycogen storage, and conversion tolipid)during 7 d ofprogressive bohydrate overfeeding(n 3).
-) =
car-
10
11
12
Days
protocol (PSMF = protein-sparing modified fast; HFLE = high-fat, low-energy diet [--7 MJ]) and the changes daily metabolizable energy intake -, energy expenditure D, positive energy balance 0, and negative energy balance U (n = 3, 1 SD).
FIG 1. Experimental
bodys During in
glycogen
stores
can
be
assumed
to
be
very
low.
in
the
lipoprotein
fractions
where
the very-low-density lipoproteins (VLDLS) increased from 20 to 70%. Blood urea was N decreased on the high-carbohydrate, low-fat diet, (end of day 2 of overfeeding), carbohydrate oxidation creased markedly on the hypocaloric high-protein diet, and storage became insufficient to dispose of all of the and returned to control concentrations at the end of the ingested carbohydrate. The excess was disposed of by experiment. Only very slight changes were observed in conversion to fat, ie, de novo lipogenesis. During the last the thyroid hormone concentrations and these can be cx. -
carbohydrate overfeeding the rate of glycogen storage was initially large, decreasing as the stores became saturated. The maximum increases in stored glycogem observed were 1 146, 629, and 654 g (in subjects 1,2, and 3, respectively) with a mean of 810 g. Saturation of it the glycogen stores occurred on day 4 of carbohydrate overfeeding for subjects 2 and 3 and on day 5 for subject 1 When the glycogen stores had increased by 500 g in-
plained
by the
short
duration
ofthe
experiment.
3 d ofoverfeeding,
total
carbohydrate
utilization
(ie,
oxi-
dation and glucose conversion to fat) was very that which was ingested. Within the limitations methods used, these results demonstrate that the drate balance was again achieved.
balance
subjects
(1 SD)
Substrate
Substra Day 1 2 3 4 5 6 7 8 9 10 11 12 13 14
S
te entering Fat 1667 12848 1176 5619 9713 8124 7814 9423 10223 6923 102 112 11328 13521
the system CHO 2918 4320 2816 73712 81378 84335 86858 93384 93245 98143 0 0 3314 497 Protein
Balance
Fat CHO
Protein 725 5016 4924 8218 934 1049 10214 11723 1226 12411 12610 12610 6420 6518
Negative
10116 10412 827 8217 8123 8823 1017 987 11511 1454 13721 1216
16446 4962 -3038 -4537 -8117 -14052 -13726 -14914 -4384 8420
7440 39887 62296 67798 79283 950158 962102 101037 49161 22359
-5231 -2329 1127 238 2216 2910 223 265 111 -207
-4741 743 12725 12628 16012 23566 23917 21820 5486 -7322
-4648 33982 19253 16674 7631 -18123 -3064 -296 -49161 -22359
values
represent
CARBOHYDRATE
DISPOSAL
IN
OVERFEEDING
245
exhaustion
445
C
and
he calculated
However,
values
by
ranging
using known
from
3 1 5 to
for
g carbohydrate.
values
the glycogen content of muscle and liver, he calculated that his subjects (mean body weight72 kg) should have had maximal values of 700 glycogen. g Bj#{246}rntorp and 0 Sj#{246}str#{246}m (22) came to the same conclusion using similar Ca a calculations but suggested that a further 100 g could be Cl, a, stored with 2 wk ofcarbohydrate overfeeding or by using C a, the glycogen-loading technique. Bergstrom et al (1) re0 ported values in the range 500-800 g in some of their a 5 subjects who followed the glycogen-loading technique. If z this glycogen was derived from muscle, as suggested by Olsson and Saltin (23), the addition of liver glycogen would increase their values to those observed in the presFIG 3. Average 24-h nonprotein respiratory quotients day 3 of a on ent study. high-fat, low-carbohydrate diet, during carbohydrate overfeeding, and Although the values reported in this study may seem for 2 d while on a PSMF devoid ofcarbohydrate. (n 3, i SD). surprising the metabolic balance data does agree with the observed body weight changes. At the end of the period after the glycogen stores had been reBy adding the negative carbohydrate balances at theoverfeeding slightly by the high rate oflipogenesis and carboend of the experiment, it was possible to obtain a value duced oxidation, body weight had increased by 4.6 kg for the amount of glycogen utilized. During this period hydrate and 700 g glycogen remained. Assuming that glycogen is 897, 89 1, and 752 g were utilized by subjects 1, 2, and 3, with two to four times its weight ofwater (23, 24), respectively. These results suggest that subjects 2 and stored 3 kg of the change in body weight can be achad not depleted their glycogen stores completely before --2. 1-3.5 for. Cumulative gains of body fat by de novo carbohydrate overfeeding began and that they still con- counted lipogenesis and from that which was provided in the diet tamed 100-200 at that time. g to 1. 1 kg fat. Thus with the 665 g increase in From these data it would seem that the glycogen stores amounted mass indicated by a gain of 1 33 g protein, we can maximally accommodate 800-900 g of carbohy- lean body can account for the 4.6 kg increase body in weight. In a drate and perhaps as much as 1-1 kg in trained 1 athmanner it is possible to account for 70% of the letes. These results are among the highest glycogen- similar lost during the2-d hypocaloric diet at the end of storage values reported in the literature. Hedman (21)weight the experiment. used respiratory-exchange measurements to calculate carbohydrate oxidation and hence glycogen depletion in Initially large glycogen storage (340 g/d) on the day 1 ofcarbohydrate overfeeding was observed during carbofour well-fed, trained cross-country skiers who skied to
0 = .
a,
measured during
(i 4 end
SD)
Day
Glucose (mmol/L) Insulin(pmol/L)
Free
high fat
4.0 0.4 507 984537
Day 6
5. 1 0.2 11536 321335 1.40.4 4.2 0.8
-
Day 9
4.9 0.2 13629 399434 5.30.8 4.7 0.8 5616 2811 164 4.2 2.53 87 3.5
Day
1 5 end
test
4.8 0.3 5714 687283 0.90.3 6.6 1.2
fatty acids
(imol/L)
Triglycerides
0.80.4 5.3 1.2 188 5910 234 6.9 1.4 1.86 0.38 11720 2.0 1.3 diet; high lipoprotein; CHO, HDL,
5.8 0.9 6824 2016 129 4.2 0.9 2.39 0.58 10036 2.7 1.4
6.4 0.9
-
T3 total (nmol/L)
T4total(nmol/L) TSH(mU/L)
2.22
0.27
9620 2.60.9
10.0
1.4
2.0.3 1 10
87 18 2.20.8
163 6410 208 7.0 1.5 2.29 0.46 101 13 2.2 1.0 fast; VLDL, T4, thyroxine; very-low-
fat diet; PSMF, protein-sparing modified BUN, blood nitrogen; urea T3, triodothyronine;
TSH,
thyroid
stimulatmng
hormone.
246
ACHESON
ET AL
hydrate refeeding after starvation (2) and after exhaus- is limited even during carbohydrate overfeeding, we tive exercise (25). The decreasing ability of the body to demonstrated that this pathway can readily dispose of store glycogen may be mediated by inhibition of glyco- nearly 500 g of glucose per day. Furthermore, the large gem synthetase activity with increasing glycogem concem- excess of carbohydrate entering the organism did not even cause excessive increases in circulating glucose contratioms (25, 26). We (6, 7) and others (5) demonstrated that humans centration. cam ingest relatively large amounts ofcarbohydrate withAs shown in Figure 1, the subjects energy expendiout initiating de novo lipid synthesis at rates exceeding tures increased markedly during the carbohydrate concomitant fat oxidation. These results are consistent overfeeding period. Because the experimental protocol with in vitro data demonstrating very low fatty acid syn- aimed at initially depleting their glycogen stores, the subthase activity in human liver and adipose tissue (27) even jects energy expenditure on day 3 is somewhat less than after the ingestion of a carbohydrate-rich diet for 3 d. their maintenance energy expenditure. The latter cam be However, these authors did observe elevated fatty acid estimated at 10 MJ/d (2400 kcal/d), ie, the observed ensynthase activities in certain situations where long-term ergy expenditure on day 3 (9.66 MJ/d) plus 10% of the deficit on that day (ie, 3.96 MJ X 10%0.4 MJ), fat-free diets were being received, eg, parenteral nutri- energy for the thermic effect ofthat amount of food. tion. It is precisely under such conditions that high rates to account of de novo lipid synthesis were observed with indirect By day 7 on the high-carbohydrate, low-fat diet, their 24h energy expenditures hadincreased by 3.5 MJ/d (840 calorimetry (28). By extrapolating from in vitro data, Bj#{246}rntorp and kcal/d). This 35% increase is one ofthe most substantial Sj#{246}str#{246}malso concluded (22) that de movo fatty acid syn- diet-induced increases in energy expenditure demonstrated in man. It is of interest to assess how much of thesis from carbohydrate is a quantitatively insignificant pathway in the whole human organism. They presumed this food-induced thermogenesis is due to the obligatory that it remained so even during carbohydrate overfeed- costs incurred for nutrient storage. Considering that fasting where excess carbohydrate would cause hyperglyceing blood glucose levels remained in the normal range occurred during the entire day, we mia and hyperinsulinemia and eventually glucose intol- and that lipogenesis erance. In the present study, postpramdial plasma glucose assumed that 80% of the carbohydrate consumed was and insulin concentrations were not measured during converted to glycogen before being used for energy proor lipogemesis. Carbohydrate stored as glycogem the carbohydrate overfeeding days but no glucosuria was duction the expenditure of 2 mol ATP per glucose moiever observed. However, fasting concentrations were requires measured every other morning. Fasting glycemia as w ety converted into glycogen plus 0.5 mol for the cost of normal (up to 5. 1 mmol/L) but insulin concentrations active transport in the gut and other phenomena, such rose from 50 7 to 144 50 pmol/L. as digestive enzyme synthesis andut motility g (3 1). BeIn addition to providing an assessment of the bodys cause glucose oxidation yields 36 mol ATP, the cost of maximal glycogem storage capacity, this study also demglycogen synthesis consumes 2.5/36 or 7% ofthe glucose stored as glycogem. The transformation ofglycogem into onstrates that de novo lipogemesis can become a major metabolic pathway for the disposal ofexcess glucose car- fatty acids, the subsequent esterification before export bons. This is not only evident from the respiratory cx-from the liver, and them triglyceride storage in adipose tissue consume additional ATP, estimated at 18%. Thus change data but also from the increases observed in of the glucose channelled into de plasma triglyceride concentrations and the proportion of-25% of the energy plasma VLDL. Because very little triglyceride was pro- novo lipogemesis can be expected to be needed for this process. vided in the diet at this time, it must have originated as newly formed triglyceride in the liver, which is the princiOfthe energy consumed in excess ofmaintenance en75% was retained and 25% dissipated. Such a high pal site ofde novo lipid synthesis in man (29). Our labo- ergy, ofenergy consumed in excess can only ratory and others (5, 27, 30) showed that de novo lipo- rate ofdissipatiom be about by conditions leading to the induction genesis does not contribute to increasing the body fat brought ofhigh rates ofcarbohydrate conversion into fat. Indeed, stores even when very large amounts of carbohydrate in daily energy expenditure was only 8% (500 g) are occasionally consumed. Glycogen storage fol- the increase the day 1 before lipogenesis became necessary for lowed by high subsequent rates ofglucose oxidation camduring of some of the excess carbohydrate calories easily accommodate the daily ingestion ofrelatively large the storage consumed. Subsequently, when the nonprotein respiraamounts of carbohydrate without there being a need to tory quotient became markedly > 1 .0, energy expendiconvert carbohydrate to fat. causing the dissipation of nearly 30% Our data suggest that glycogen stores must increase byture rose further, 500 g before appreciable de novo lipogenesis begins. ofthe calories consumed in excess. our findings indicate that the bodys glycogen Provided that massive amounts of carbohydrate con- Finally, filled under normal ad libitinue to be ingested, the glycogen stores become satu- stores are far from completely tum conditions. Ifthe glycogen stores are not limited by rated so that the only way of disposing of additional cxsaturation ofthe glycogen storage capacity, one cess carbohydrate is by fat synthesis in addition to maxi- physical mal use ofglucose for energy generation. Although it has can more readily envision that individual differences and responsiveness to food palatability and accessibility may been suggested that the capacity for de movo lipogenesis
=
CARBOHYDRATE
DISPOSAL
IN OVERFEEDING
6-phosphate
enzymic
247
of
influence to a considerable extent the range within which glycogen stores are spontaneously maintained. In turn this will affect the relative contributions that glucose and 15. free fatty acids tend to make to the metabolic fuel mix used for energy generation and the conditions for which 16. the steady state of body weight maintenance tends to be achieved (32). 0
17.
Herbert
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Dole VP, Meinertz H. Microdetermination of long chain fatty We thank the dieticians Fiona Hunter, Carolyne Summerbell, and acids in plasma and tissues. J Biol Chem l960;235:2595-9. Nicole Baudat; A Beccarelli, J Braissant, D Kock, and K Rocafi for 18. Bucolo 0, David H. Quantitative determination ofserum triglyctheir technical assistance; and Dr J Frei, Dr T Lemarchand, E Temler, erides by the use ofenzymes. Gin Chem 1973; 19:476-82. and D Penseyres for the blood analyses. 19. Technicon. Technicon autoanalyser methodology. Simultaneous
glucose/BUN
20. Southgate
Method
DAT, Durnin
N-l6b.
JVOA.
Tarrytown,
Calorie
NY: Technicon,
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1967.
An cx-
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