The lipostat, hyperphagia and catch-up growth

M Jobling & S J S Johansen

NFH, University of Tromsù, 9037 Tromsù, Norway

Correspondence: M Jobling, NFH, University of Tromsù, 9037 Tromsù, Norway

Abstract

The hypothesis that long-term energy intake is

matched to energy expenditure arose during the

1950s, and this formed the basis of the lipostatic

model for the control of food intake in mammals.

This gave rise to an additional hypothesis that body

weight varies little over adult life because body fat, a

variable related to body mass, is regulated. There is

now a large body of evidence that adipose tissue

plays a role in the regulation of feeding and body

weight in mammals, and the study of the mechan-

isms by which the brain monitors the signals arising

from the adipose tissue is currently a major area of

research. After a period of nutritional restriction, a

number of compensatory responses are invoked,

and these result in hyperphagia, rapid weight

increase and the repletion of energy reserves.

However, the extent to which animals recover lost

body weight has been reported to vary between

studies. It is hypothesized that the rate at which

animals replete their lipid reserves during catch-up

growth may in¯uence the hyperphagic response

and, hence, whether or not there is complete

recovery of body weight. Preliminary tests carried

out using some data collected in studies of catch-up

growth in salmonids appear to provide support for

the model, but more experimental studies are

needed to provide rigorous testing.

The lipostat

The concept that body weight and adipose mass are

subject to negative feedback control arose about

50 years ago, when it was hypothesized that long-

term (weeks±months) energy intake was actively

matched to energy expenditure. When the energy

balance (the difference between energy intake and

expenditure) of animals was changed experimen-

tally, the changes in body weight induced by such

interventions resulted in the activation of compen-

satory responses that eventually returned body

weight to a value close to the original. For example,

a period of imposed food restriction resulted in

weight loss but, when food was made available

again, the animals overate, i.e. became hyperpha-

gic, until body weight returned to a level similar to

that before restriction. Thus, it was considered that,

although body weight sensu stricto may not be

regulated, a variable, or set of variables, correlated

to body weight must be regulated.

These observations set the stage for Kennedy's

lipostatic model for the control of food intake and

body composition (Kennedy 1953). It was hypothe-

sized that humoral signals generated in proportion

to adipose mass (size of lipid reserves) provide input

(feedback) to the areas of the brain that control

feeding and energy expenditure. In this regulatory

process, there may be alterations in food intake,

spontaneous activity, metabolism, metabolic ef®-

ciency and thermogenesis. Although there is gen-

eral agreement that these responses are co-

ordinated by the brain, the way in which the brain

monitors body adiposity and invokes the compen-

satory responses are still not completely understood,

and a variety of signalling mechanisms have been

proposed (Hervey 1969; Weigle 1994; Cabanac &

Richard 1996; Matson, Wiater & Weigle 1996;

Friedman 1998). In his lipostatic model, Kennedy

(1953) proposed that a change in energy balance

suf®cient to alter adiposity elicited a compensatory

change in food intake as a result of the change in

the amount of negative feedback. Thus, after a

period of food restriction, the negative feedback

signals that inhibit feeding are reduced because of

fat loss. The result is elevated food intake that is

R

# 1999 Blackwell Science Ltd 473

Aquaculture Research, 1999, 30, 473±478

maintained until the level of fat and, hence, the

negative feedback signals return to normal.

Evidence that one such negative feedback signal

was a circulating factor came from parabiosis

studies. In parabiosis, two animals are physically

joined to one another so that they share a cross-

circulation of blood. When normal, lean rats were

joined to rats rendered obese by hypothalamic

lesions, the normal rats reduced their food intake

and would starve to death if not separated from

their obese partners (Hervey 1959). This provided

strong evidence that a circulating, `satiety' factor

from the lesioned, obese rat was affecting the

normal rat. In other words, the obese rat seemed

to secrete a circulating endocrine signal that crossed

over to the normal, lean partner and inhibited its

food intake, but the hypothalamic lesion had

rendered the obese animal unresponsive to the

circulating signal, so that it continued to feed and

accumulate body fat. Later, it was shown that when

rats with diet-induced obesity were parabiosed with

normal, non-obese rats, the food intake of the

normal rats decreased, and there was a reduction in

the body fat of these animals. These changes were

attributed to an energy-stabilizing, satiety factor

carried in the circulation from the obese to the

normal rat (Nishizawa & Bray 1980). Similar

changes were also demonstrated when tube-fed

obese rats were parabiosed with normal partners

(Harris & Martin 1984). The results of these

experiments led to the conclusion that the regula-

tion of both food intake and body energy reserves in

the form of fat was probably mediated by a blood-

borne factor that acted at the level of the

hypothalamus. Evidence is now accumulating in

favour of the hypothesis that an `adipose tissue

factor' (ob protein or leptin) may play a role in the

co-ordination of ingestive behaviour and energy

balance in mammals, but this factor is not seen as

working in isolation (Matson et al. 1996; Blum

1997; Friedman 1998; Hossner 1998; Schwartz &

Seeley 1997).

Catch-up growth

It is now widely accepted that adipose tissue mass

in¯uences ingestive behaviour and food intake in

mammals (Weigle 1994; Matson et al. 1996; Blum

1997; Schwartz & Seeley 1997; Friedman 1998;

Hossner 1998), and there is also evidence that the

size of the body fat stores may have an in¯uence on

feeding in salmonid ®shes (Metcalfe & Thorpe 1992;

Jobling & Miglavs 1993; Shearer, Silverstein &

Plisetskaya 1997). Furthermore, the responses of

®sh after a period of nutritional restriction seem to

resemble those observed in mammals: hyperphagia,

rapid growth and the repletion of energy reserves

(Broekhuizen, Gurney, Jones & Bryant 1994;

Jobling 1994). Thus, ®sh will usually consume

more food and grow faster than expected after a

period of fasting, compensating for lost growth and

returning body mass to a level that approaches that

of conspeci®cs that have had continuous access to

food (Broekhuizen et al. 1994; Jobling 1994). The

extent to which fasted ®sh display hyperphagia on a

return to adequate feeding conditions may be

related to the degree to which their energy reserves

were depleted during fasting, and there may be an

inverse relationship between post-fast food intake

and the size of the lipid depots (Jobling & Miglavs

1993).

Hervey (1969) hypothesized that the long-term

stability of body weight in adult mammals was

mediated through the regulation of a variable

correlated to body mass. Broekhuizen et al. (1994)

extended this hypothesis in a two-compartment

model in which tissues could be broadly divided into

reserves (fat depots and the mobilizable parts of the

musculature) and structural components (skeleton,

circulatory and nervous tissue): it was proposed that

it is the balance between these two components that

is regulated, and that shifts in the balance would

invoke compensatory changes. Thus, it was en-

visaged that the responses observed in animals

undergoing catch-up growth could be related to a

monitoring of the `instantaneous nutritional state',

as re¯ected in the ratio of reserves to structural

tissues. In most animals, the fat depots represent the

easily mobilized energy reserves, and the lean body

mass (LBM) incorporates the structural tissues, so

the ratio fat:LBM may comply with an indicator of

nutritional state (although it must be borne in mind

that LBM will also include a mobilizable compo-

nent).

Among ®sh species, catch-up or compensatory

growth has been reported for salmonids, cyprinids,

pleuronectids, gadoids and centrarchids (e.g.

Weatherley & Gill 1987; Miglavs & Jobling 1989a;

Bejda, Phelan & Studholme 1992; Russell &

Wootton 1992; Broekhuizen et al. 1994; Jobling,

Melùy, dos Santos & Christiansen 1994; Bull &

Metcalfe 1997; Hayward, Noltie & Wang 1997;

Nicieza & Metcalfe 1997), but responses have been

inconsistent. In other words, recovery of lost body

L

474 # 1999 Blackwell Science Ltd, Aquaculture Research, 30, 473±478

Hyperphagia and catch-up growth M Jobling & S J S Johansen Aquaculture Research, 1999, 30, 473±478

weight has been reported to be partial in some cases,

whereas complete catch-up has been reported in

others (Fig. 1), and a few cases of `overcompensa-

tion' have also been observed. The lipostatic model

for the negative feedback control of body adiposity

(Kennedy 1953) might be able to contribute to an

explanation of these apparently disparate results.

For example, in animals that repleted their body

lipid reserves rapidly during catch-up growth, there

would be both a rapid ablation of hyperphagia

resulting from the increase in the negative feedback

signals arising from the accumulating adipose tissue

mass and a rapid restoration of the fat:LBM ratio.

The net result would be an incomplete recovery of

body weight, relative to fully fed controls. On the

other hand, if lipid accumulation took place more

slowly during catch-up, the hyperphagic response

would be of longer duration, and changes in

fat:LBM would occur gradually, enabling a complete

restoration of body weight. In cases of a very slow

repletion of lipid reserves, body weight `overcom-

pensation' might be predicted because the imbal-

ance in the fat:LBM ratio would remain for a

prolonged period.

Test of the model

A test of this model requires information about the

changes in both body mass and tissue composition

that occur in animals that are undergoing catch-up

growth. Such information is available from studies

of compensatory growth in Arctic char Salvelinus

alpinus L. (Miglavs & Jobling 1989a,b). Juvenile,

hatchery-reared char (initial weight » 8.5 g) were

either provided with full rations for 16 weeks or

feed-restricted for 8 weeks and then provided with

full rations for 8 weeks. Samples were taken for

proximate body composition analysis at the start of

the experiment. Fully fed controls were sampled at

the end of the experiment, and samples of feed-

restricted ®sh were taken after 8 and 16 weeks

(Miglavs & Jobling 1989a,b).

The fully fed controls increased in body mass from

» 8.5 to » 54 g during the 16-week trial and, at

8 weeks, weighed » 20 g. Adiposity of these ®sh

increased during the course of the study, the ratio of

body fat to lean body mass (fat:LBM) increasing

from 0.063 at the start to 0.079 after 16 weeks on

full rations (Fig. 2).

For the ®rst 8 weeks, the feed-restricted ®sh were

fed a ration that was close to maintenance. They

increased slightly in weight (from » 8.5 to » 9.5 g),

but there was a fall in the fat:LBM from the initial

0.063 to 0.047 after 8 weeks on restricted rations

R

Figure 1 Growth of `normal' animals (idealized growth

curve) and deviations from the idealized growth curve

during periods of restricted feeding and catch-up, recovery

or compensatory, growth. A feeding restriction is imposed

at time point A, and animals are returned to full, or ad

libitum, feeding at point B. After the return to full feeding,

growth rate is initially rapid, but then slows. The recovery

of body weight may be either complete or partial.

Figure 2 Changes in body weight and composition of

juvenile Arctic char Salvelinus alpinus L. during 16 weeks

of full feeding (full: sampling at 0 and 16 weeks) or

8 weeks on a restricted ration followed by 8 weeks on full

rations (restricted: sampling at 0, 8 and 16 weeks). LBM,

lean body mass. Recalculated from data in Miglavs &

Jobling (1989a,b).

# 1999 Blackwell Science Ltd, Aquaculture Research, 30, 473±478 475

Aquaculture Research, 1999, 30, 473±478 Hyperphagia and catch-up growth M Jobling & S J S Johansen

(Fig. 2). After the introduction of full feeding, these

®sh became hyperphagic and displayed marked

increases in growth rate (Miglavs & Jobling

1989a). The hyperphagia had ablated by the end

of the trial, and growth rates had also declined to

levels similar to those of the fully fed controls

(Miglavs & Jobling 1989a). However, the body

weights of these ®sh were only » 35 g, so the

compensatory responses had resulted in a partial

recovery of body weight in comparison with the

fully fed controls (Fig. 2).

Comparison of proximate body compositions of

the two groups of ®sh at the end of the trial revealed

similarities in adiposity (fat percentage: 7.4 vs.

7.2%) and fat:LBM (0.079 vs. 0.078) (Fig. 2), which

would have been predicted if lipostatic control of

feed intake were important in governing the growth

of feed-restricted ®sh during the recovery phase.

Additional, albeit circumstantial, evidence for the

idea of the involvement of lipostatic mechanisms in

the regulation of feeding and growth may be

provided by data obtained in a study of seasonal

lipid dynamics of wild, anadromous char

(Jùrgensen, Johansen & Jobling 1997).

Anadromous char undertake annual feeding migra-

tions to the sea during the summer months and

spend 40±50 days in sea water before returning to

fresh water to overwinter.

Char from the north Norwegian population

examined by Jùrgensen et al. (1997) increased

substantially in body weight during the summer

(immature ®sh from about 300 to 600 g; maturing

®sh from 500 to 800 g), and the weight of body lipid

increased approximately ®vefold (Jùrgensen et al.

1997). Fish that were descending to the sea in

spring were lipid depleted (fat:LBM of 0.021 in

males and 0.024 in females) (Fig. 3), and lipid stores

were repleted during the course of the summer.

Analysis of the body composition of char re-entering

fresh water at the end of the summer revealed that

the fat:LBM ratio of both males (0.063) and females

(0.072) (Fig. 3) was within the range of those of

fully fed, hatchery-reared juvenile char (0.063±

0.079) (Fig. 2). Thus, even though circumstantial,

this evidence seems to suggest that the wild,

anadromous char ceased feeding in the sea and re-

entered fresh water once their lipid reserves were

repleted.

Preliminary results of a study carried out on post-

smolt Atlantic salmon Salmo salar L. (initial weight

» 75 g) reveal changes in body composition that

may occur in ®sh undergoing complete compensa-

tion after a period of feed restriction (S J S Johansen,

M Ekli & M Jobling, pers. comm.). Fully fed ®sh were

fed in excess throughout the 16-week trial. For the

®rst 8 weeks, the restricted group was fed half the

ration predicted to support maximum growth and,

during the second half of the trial, these ®sh were

given an unlimited feed supply.

During the restriction phase, the increase in body

weight of the feed-restricted ®sh was only 65% of

that of the fully fed controls. There were differences

between the groups in both LBM (controls 157 g;

restricted 126 g) and proximate chemical composi-

tion (fat:LBM of controls 0.080; restricted 0.066)

(Fig. 4).

By the end of the trial, the ®sh in both groups

weighed » 275 g. In other words, during the

recovery period, the restricted group had increased

growth rate and fully compensated for the poorer

growth during the ®rst half of the trial. The

differences in LBM seen at the end of the feed-

restriction phase had disappeared (LBM controls

252 g; restricted 258 g), and differences in relative

lipid content had been reduced (fat:LBM controls

0.094; restricted 0.087).

Taken together, these observations indicate that

feed restriction results in ®sh with a lower fat

content and suggest that the rate at which body fat

is accumulated may have some regulatory role

during catch-up growth. This seems to be in

accordance with the lipostatic model. On the other

hand, there are some reports that ®sh with fully

L

Figure 3 Body weights and compositions of wild,

anadromous male and female Arctic char Salvelinus

alpinus L. during spring descent to sea water (Descend)

and during the return to fresh water in late summer

(Ascend). LBM, lean body mass. Recalculated from data

in Jùrgensen, Johansen & Jobling (1997).

476 # 1999 Blackwell Science Ltd, Aquaculture Research, 30, 473±478

Hyperphagia and catch-up growth M Jobling & S J S Johansen Aquaculture Research, 1999, 30, 473±478

repleted lipid reserves continue to display catch-up

growth (Bull & Metcalfe 1997; Nicieza & Metcalfe

1997), something that would con¯ict with the

lipostatic model. However, in these latter studies,

lipid content was not monitored directly, but was

estimated using a series of morphometric measure-

ments (Simpson, Metcalfe & Thorpe 1992). When

®sh are undergoing catch-up growth and are

envisaged to be depositing reserves and structural

tissues differently from individuals that are growing

normally, it is open to question whether biometry

will provide an adequate assessment of the size of

the body lipid reserves. Thus, the evidence may be

equivocal, and further tests are required.

Conclusions

The size of the body lipid reserves in¯uences feed

intake in mammals via negative feedback signals to

the central nervous system, and this forms the basis

of the lipostatic model for the regulation of ingestive

behaviour, body weight and body composition. The

size of the body fat stores may have an in¯uence on

feeding in salmonid ®shes, and there is some

evidence for lipostatic involvement in the regulation

of the hyperphagic response seen in ®sh that are

undergoing catch-up growth after a period of

nutritional deprivation. Although a model incorpor-

ating lipostatic regulation would seem to offer a

simple and attractive explanation for the changes in

feed intake and growth observed in ®sh undergoing

catch-up growth, more rigorous testing of the model

is required via studies in which changes in feed

intake, body mass and tissue composition are

examined simultaneously.

References

Bejda A.J., Phelan B.A. & Studholme A.L. (1992) The effect

of dissolved oxygen on the growth of young-of-the-year

winter ¯ounder, Pseudopleuronectes americanus.

Environmental Biology of Fishes 34, 321±327.

Blum W.F. (1997) Leptin: the voice of the adipose tissue.

Hormone Research 48 (Suppl. 4), 2±8.

Broekhuizen N., Gurney W.S.C., Jones A. & Bryant A.D.

(1994) Modelling compensatory growth. Functional

Ecology 8, 770±782.

Bull C.D. & Metcalfe N.B. (1997) Regulation of hyperpha-

gia in response to varying energy de®cits in over-

wintering juvenile Atlantic salmon. Journal of Fish

Biology 50, 498±510.

Cabanac M. & Richard D. (1996) The nature of the

ponderostat: Hervey's hypothesis revived. Appetite 26,

45±54.

Friedman J.M. (1998) Leptin, leptin receptors and the

control of body weight. Nutrition Reviews 56, S38±S46.

Harris R.B.S. & Martin R.J. (1984) Speci®c depletion of

body fat in parabiotic partners of tube-fed obese rats.

American Journal of Physiology 247, R380±R386.

Hayward R.S., Noltie D.B. & Wang N. (1997) Use of

compensatory growth to double hybrid sun®sh growth

rates. Transactions of the American Fisheries Society 126,

316±322.

Hervey G.R. (1959) The effects of lesions in the hypotha-

lamus in parabiotic rats. Journal of Physiology 145,

336±352.

Hervey G.R. (1969) Regulation of energy balance. Nature

223, 629±631.

Hossner K.L. (1998) Cellular, molecular and physiological

aspects of leptin: potential application in animal

production. Canadian Journal of Animal Science 78,

463±472.

Jobling M. (1994) Fish Bioenergetics. Chapman & Hall,

London.

Jobling M. & Miglavs I. (1993) The size of lipid depots ± a

factor contributing to the control of food intake in Arctic

R

Figure 4 Body weight and composition of post-smolt

Atlantic salmon Salmo salar L. during 16 weeks of full

feeding (control: sampling on 23 July and 18 September)

or 8 weeks on a restricted ration followed by 8 weeks on

full rations (restricted: sampling at the end of the

restriction phase on 23 July and on 18 September). LBM,

lean body mass. Unpublished data from S J S Johansen,

M Ekli & M Jobling.

# 1999 Blackwell Science Ltd, Aquaculture Research, 30, 473±478 477

Aquaculture Research, 1999, 30, 473±478 Hyperphagia and catch-up growth M Jobling & S J S Johansen

charr, Salvelinus alpinus? Journal of Fish Biology 43,

487±489.

Jobling M., Melùy O.H., dos Santos J. & Christiansen B.

(1994) The compensatory growth response of the

Atlantic cod: effects of nutritional history. Aquaculture

International 2, 75±90.

Jùrgensen E.H., Johansen S.J.S. & Jobling M. (1997)

Seasonal patterns of growth, lipid deposition and lipid

depletion in anadromous Arctic charr. Journal of Fish

Biology 51, 312±326.

Kennedy G.C. (1953) The role of depot fat in hypothalamic

control of food intake in the rat. Proceedings of the Royal

Society B 140, 578±592.

Matson C.A., Wiater M.F. & Weigle D.S. (1996) Leptin and

the regulation of body adiposity. Diabetes Reviews 4,

488±508.

Metcalfe N.B. & Thorpe J.E. (1992) Anorexia and defended

energy levels in over-wintering juvenile salmon. Journal

of Animal Ecology 61, 175±181.

Miglavs I. & Jobling M. (1989a) Effects of feeding regime on

food consumption, growth rates and tissue nucleic acids

in juvenile Arctic charr, Salvelinus alpinus, with parti-

cular reference to compensatory growth. Journal of Fish

Biology 34, 947±957.

Miglavs I. & Jobling M. (1989b) The effects of feeding

regime on proximate body composition and patterns of

energy deposition in juvenile Arctic charr, Salvelinus

alpinus. Journal of Fish Biology 35, 1±11.

Nicieza A.G. & Metcalfe N.B. (1997) Growth compensation

in juvenile Atlantic salmon: responses to depressed

temperature and food availability. Ecology 78, 2385±

2400.

Nishizawa Y. & Bray G.A. (1980) Evidence for a

circulating ergostatic factor: studies on parabiotic rats.

American Journal of Physiology 239, R344±R351.

Russell N.R. & Wootton R.J. (1992) Appetite and growth

compensation in the European minnow, Phoxinus

phoxinus (Cyprinidae), following short periods of food

restriction. Environmental Biology of Fishes 34, 277±

285.

Schwartz M.W. & Seeley R.J. (1997) The new biology of

weight regulation. Journal of the American Dietetic

Association 97, 54±58.

Shearer K.D., Silverstein J.T. & Plisetskaya E.M. (1997)

Role of adiposity in food intake control of juvenile

chinook salmon (Oncorhynchus tshawytscha).

Comparative Biochemistry and Physiology A 118, 1209±

1215.

Simpson A.L., Metcalfe N.B. & Thorpe J.E. (1992) A simple

non-destructive biometric method for estimating fat

levels in Atlantic salmon, Salmo salar. Aquaculture and

Fisheries Management 23, 23±29.

Weatherley A.H. & Gill H.S. (1987) The Biology of Fish

Growth. Academic Press, London.

Weigle D.S. (1994) Appetite and the regulation of body

composition. FASEB Journal 8, 302±310.

L

478 # 1999 Blackwell Science Ltd, Aquaculture Research, 30, 473±478

Hyperphagia and catch-up growth M Jobling & S J S Johansen Aquaculture Research, 1999, 30, 473±478