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The metabolic profile was analyzed during constant fluctuating thermal regimes the beetles had daily pulses at higher temperatures that enabled them to recover and compared with con-stant

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tropical beetles exposed to fluctuating thermal regimes

L Lalouette1, V Kosˇta´l2, H Colinet3, D Gagneul4,5and D Renault1

1 UMR CNRS 6553, Universite´ de Rennes 1, Rennes, France

2 Institute of Entomology, Biology Centre AS CR, C ˇ eske´ Budejovice, Czech Republic

3 Unite´ d’Ecologie et de Bioge´ographie, Centre de Recherche sur la Biodiversite´, Universite´ catholique de Louvain, Louvain-la-Neuve, Belgium

4 UMR CNRS 6026, Universite´ de Rennes 1, Rennes, France

5 Department of Plant Biology, Michigan State University, East Lansing, MI, USA

Environmental stress deleteriously affects every aspect

of an ectotherm’s biological function because it

dis-rupts homeostasis, and is of sufficient magnitude to

impose geographical limits on where animal life can

occur, even if the other environmental parameters are

permissive [1,2] As arthropods’ development and

sur-vival are intimately linked to environmental

tempera-tures, these organisms have evolved a diversity of

morphological, physiological and behavioural

adapta-tions [3] Several authors have contributed to the

increased knowledge of arthropods’ cold-hardiness over the past years [4–7], but studies were usually per-formed under controlled conditions by measuring organisms’ cold-tolerance at low but constant tempera-tures Fluctuating thermal regimes (FTRs) are, how-ever, typical in natural habitats, and yearly active species may exploit intermittent periods of favourable temperatures in order to feed, develop and repair low temperature injuries (chill injuries, i.e damage caused

by low temperatures without formation of ice crystals)

Keywords

amino acid; fluctuating thermal regime;

insect; polyol; sugar

Correspondence

D Renault, UMR CNRS 6553, University of

Rennes 1 Baˆt 14A, 263 Avenue du Gal

Leclerc, CS 74205, 35042 Rennes Cedex,

France

Fax: +33 2 23235046

Tel: +33 2 23236627

E-mail: david.renault@univ-rennes1.fr

Website: http://ecobio.univ-rennes1.fr

(Received 13 November 2006, revised 26

January 2007, accepted 1 February 2007)

doi:10.1111/j.1742-4658.2007.05723.x

Environmental stress deleteriously affects every aspect of an ectotherm’s biological function Frequent exposure of terrestrial insects to temperature variation has thus led to the evolution of protective biochemical and phy-siological mechanisms However, the phyphy-siological mechanisms underlying the positive impact of fluctuating thermal regimes (FTRs) on the fitness and survival of cold-exposed insects have not been studied We have thus investigated the metabolic changes in adults of the beetle Alphitobius diaperinus in order to determine whether FTRs trigger the initiation of a metabolic response involving synthesis of protective compounds, such as free amino acids (FAAs) and polyols The metabolic profile was analyzed during constant fluctuating thermal regimes (the beetles had daily pulses at higher temperatures that enabled them to recover) and compared with con-stant cold exposure and untreated controls The increase of several essential amino acids (Lys, Iso, Leu, Phe and Trp) in cold-exposed beetles supports the conclusion that it results from the breakdown of proteins Some FAAs have been shown to have cryoprotective properties in insects, but the rela-tionship between FAAs, cold tolerance and survival has not yet been well defined Instead of considering FAAs only as a part of the osmo- and cryo-protective arsenal, they should also be regarded as main factors involved in the multiple regulatory pathways activated during cold acclimation Under FTRs, polyol accumulation probably contributes to the increased duration

of survival in A diaperinus

Abbreviations

FAA, free amino acid; FM, fresh mass; FTR, fluctuating thermal regime; HSP, heat shock protein.

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Such species may also set up physiological processes of

cold-hardening that is cued by the low temperature

but requires a stay at higher temperature for effective

expression [8]

In most species tested to date, survival rates were

con-siderably increased when insects were exposed to FTRs,

compared with those maintained under constant low

temperatures Indeed, the short bouts at a higher

tem-perature may reset the physiological state of the insects

towards the initial value [6,8–10] However, few studies

attempted to investigate the physiological and

biochemi-cal responses of insects subjected to thermal

fluctua-tions, and thus the mechanisms underlying the relative

increase of cold tolerance in insects exposed to FTRs

are poorly understood Recently, Kosˇta´l et al [11]

found that constant cold-exposed bugs of Pyrrhocoris

apterus and beetles of Alphitobius diaperinus failed to

maintain specific ion concentrations outside and inside

the cells, or across epithelia Under FTRs, however, the

primary ion pumping systems, P- and V-type ATPases,

were allowed to re-establish the ion gradients across cell

membranes and epithelia during the ‘warm’ periods [11]

The impaired function of ion pumping systems, together

with the inability to prevent⁄ restrict ion leakage down

the electrochemical gradient, led to the reduction or

unbalance of metabolites transfer This then results in

the depletion of energetic substances in cells, or in the

accumulation of potentially toxic waste substances [3]

Thermal stress strongly impacts on metabolite

con-centrations [4,12,13] Thus, metabolite changes that

occur downstream of changes in transcript or protein

levels give a good picture of the overall integrated

response of an organism [14,15] The free amino acid

(FAA) pool, which is at the centre of metabolic activity

during a variety of stress responses [16], is particularly

affected by thermal stress, and can thus indicate

chan-ges in gene and protein expression, like heat shock

pro-teins (HSPs) Indeed, it was recently found that FTRs

significantly increase the expression of HSPs during

high temperature pulses [17, L Lalouette, H Colinet,

D Siaussat & D Renault, unpublished data]

More-over, several amino acids, like Pro, Gly, Ala, and Leu,

were identified as responsive to cold stress during

con-stant cold exposure [18] They were either directly

corre-lated with stress tolerance (a causal relationship

between Pro levels and stress tolerance was found

[3,19]), or with the changes in levels of stress hormones

during thermal stress [20] However, despite their

pre-dominant role in several metabolic pathways, amino

acids were never investigated in insects exposed

to FTRs Other than amino acids, the importance of

polyols and sugars, like glycerol and trehalose, has

been emphasized regularly during insect cold

acclimation [21] However, the few studies that have attempted to investigate polyol levels in insects subjec-ted to FTRs are contradictory Indeed, cycling thermal regimes were found to increase glycerol amounts in the gall fly [22], whereas it did not differ significantly between cyclic and constant temperature regimes in the beet armyworm [23]

In the present study, we investigated the impact of cold exposure and associated metabolic changes in a year-round active beetle, A diaperinus, introduced in temperate regions from the Ivory Coast (Africa)

A diaperinus was a convenient model because it is highly chill-susceptible during cold exposures, but exhibits strong recovery capacities during the pulses at

a ‘warm’ temperature under FTRs [9] Contrasted meta-bolic responses should therefore be obtained between chilled beetles and ones that were allowed to recover daily Moreover, relatively extensive knowledge on the cold-hardiness ecology and physiology of A diaperinus has been gathered [9,11–13,24]: these studies demon-strated that its survival was progressively reduced when the temperature dropped below 8C In a more recent work, we found that beetles kept at a constant tempera-ture of 0C quickly died, whereas the effects of chilling were reversed completely when insects were kept in FTRs (5C ⁄ 22 h and 20 C ⁄ 2 h) [9] Thus, we wanted

to determine whether FTRs trigger the initiation of a metabolic response involving synthesis of protective compounds such as FAAs, polyols or HSPs The simul-taneous measurement of a large number of metabolites, relevant because the overall effect of the thermal stress

is assessed [15], was thus investigated in beetles kept under FTRs, and compared to constant cold-exposed beetles, and untreated controls

Results

Survival Lethal time for 50% of the population (Lt50) of the beetles exposed at constant 0C was 5.95 ± 0.65 days After 10 days of FTR (0C alternating with 20 C on

a 12 h basis), no mortality was observed The experi-ment was stopped after 3 weeks, and it was not possi-ble to determine the Lt50 for these beetles Longer exposures to such experimental conditions would encounter mortality unrelated to cold

Amino acids Several differences were found in metabolic profiles between insects exposed to constant temperatures and fluctuating thermal regimes

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The total FAA pool was significantly higher in control

beetles [73.19 ± 2.18 nmolÆmg)1 fresh mass (FM)]

than in constant cold-exposed (0Cc) (56.72 ± 3.31

nmolÆmg)1 FM) and 20CF0 (20C/12 hr[20 CF0]

fluctuating with 0C/12 hr[0 CF20]) ones (51.56 ±

2.35 nmolÆmg)1 FM) (P < 0.05); the total amount of

FAA was significantly higher in 0CF20 beetles

(72.58 ± 4.58 nmolÆmg)1 FM) than in 0Cc and

20CF0ones (P < 0.05)

Pro was the main amino acid found, whatever the

experimental conditions (Fig 1A,B) It is, however,

interesting to notice that it represented 35% of the

total FAA pool in beetles exposed at a constant

tem-perature of 0C, 50% of the total FAA pool at

alter-nating temperature (20CF0, 0CF20) (Fig 1A) and

>50% of the total FAA pool in control beetles Gln

and Ala were also found in high amounts in the whole

body of A diaperinus Levels of five essential amino

acids (Lys, Iso, Leu, Phe and Trp) were increased

sig-nificantly when the beetles were cold exposed (Fig 1B) No significant difference was found for Val between the four distinct thermal treatments (control,

0Cc, 0CF20and 20CF0)

Control beetles exhibited the lowest amounts of Glu and Lys, and the highest levels of Asn⁄ Ser and Arg⁄ Thr (Fig 1A,B) Gln was significantly lower in control and 0Cc beetles (P < 0.05), whereas an opposite conclusion was found with Pro (significantly higher in control and 0Ccbeetles)

Amino acid profiles in 0Ccversus 0CF20

beetles The level of several FAA differed between the 0 Cc and 0CF20 thermal treatments Ala, Gln and Pro accounted for most of the observed quantitative differ-ence; Ala and Pro being highly accumulated in the

0CF20 beetles (10.03 ± 2.14 and 37.21 ± 3.12 nmo-lÆmg)1 FM, respectively) compared with the 0Cc bee-tles (5.79 ± 1.39 and 20.78 ± 1.39 nmolÆmg)1 FM, respectively; P < 0.05) (Fig 1A) Although it was two times lower in 0Ccbeetles, Ala content was not signi-ficantly different from 0CF20 beetles (P > 0.05) Levels of Glu and Gln had opposite patterns and were significantly lower in 0CF20 than in 0Cc beetles (6.02 ± 0.66 versus 15.06 ± 1.46 nmolÆmg)1 FM, respectively, for Gln, P < 0.05) (Fig 1A) Lys was also significantly higher in 0CF20beetles (P < 0.05)

Amino acid profiles in 0CF20versus 20CF0 beetles

Several differences were observed in the amounts of amino acids between 0CF20 and 20CF0 beetles (Fig 1A,B) On the 14 amino acids detected, nine differed significantly (P < 0.05) Gln was the only amino acid that was found in significantly lower amounts in 0CF20 beetles (6.02 ± 0.66 versus 11.06 ± 0.76 nmolÆmg)1 FM) The levels of four essential amino acids (Arg⁄ Thr, Lys, Leu, Phe) and four nonessential amino acids (Asn⁄ Ser, Gly, Ala, Pro) were significantly higher in 0CF20, explaining the dif-ference observed in the total FAA pool between these two thermal treatments Again, the most important differences were recorded for Pro and Ala, which were very highly significantly reduced in 20CF0

It is interesting to notice that Gln and Ala had an opposite pattern, with the highest level in 0 Cc, the lowest level in 0CF20 and an intermediate level in

20CF0 beetles for Gln, the highest amounts in

0CF20, the lowest amounts in 20CF0and an inter-mediate situation in 0Cc beetles for Ala (Fig 1A)

Fig 1 Free amino acid body contents in A diaperinus kept at

con-stant 20 C (control), constant 0 C, and FTR (20 C ⁄ 12 h: 20 C F0 ,

and 0 C ⁄ 12 h: 0 C F20 ) (A) Nonessential amino acids, and (B)

essential amino acids Values are mean ± SE (n ¼ 7) Bars with

dif-ferent letters indicate significant differences between FAA

(P < 0.05).

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Moreover, both Ala and Pro had similar patterns in

these three thermal treatments

Sugars and polyols

Data are presented in Fig 2 Glycerol and glucose had

opposite patterns: glycerol was highly significantly

accumulated in 0CF20beetles, whereas glucose

exhib-ited the lowest amounts in these beetles (P < 0.05)

For trehalose, a trend appeared: it was detected in

lower amounts in beetles subjected to FTRs than in

control ones, whereas myo-inositol seems to be

slightly accumulated in 0CF20 beetles Mannitol was

not detected in control beetles, whereas small amounts

were found in 0CF20(0.022 ± 0.002 nmolÆmg)1FM)

and 20CF0 beetles (0.018 ± 0.003 nmolÆmg)1 FM)

Arabinitol was only detected in 0CF20beetles, but in

low amounts (0.019 ± 0.001 nmolÆmg)1 FM) No

sig-nificant differences were found for sorbitol and ribitol

(Fig 2)

Discussion

Cold survival

Though animals are regularly exposed to

thermo-vari-able environments, survival of insects subjected to

thermal fluctuating regimes had rarely been

investi-gated until some recent studies [8–10,26] When the

adults of A diaperinus were exposed to the FTRs of

0C (12 h) ⁄ 20 C (12 h), their survival was consider-ably improved (no mortality after 10 days) in compar-ison with the exposure to the constant low temperature of 0C The effect of chilling could have been mitigated simply by the significant reduction (12 h daily) of the exposure time to the low tempera-ture However, after 10 days of FTRs, the beetles had spent 5 days at 0C in total, whereas the mortality was already >30% at the same time in the constant cold-exposed beetles In earlier studies, a similar phe-nomenon was observed in several insect species [8,10,26–28], demonstrating that the positive effect of FTRs on the insect cold tolerance emerges as a general phenomenon

Literature on the physiological mechanisms underly-ing the positive impact of FTRs on the survival of cold-exposed insects is scarce Very recently, we found that the haemolymph concentrations of magnesium and sodium ions in adults of A diaperinus were either maintained relatively constant or decreased slightly during both constant cold exposure and FTRs [11] The extracellular concentration of potassium ions increased with significantly higher rates in the insects exposed to constant low temperatures than in those exposed to FTRs, and returned toward normal [K+] during the warm ‘recovery’ periods of the FTRs We speculated that this mechanism could slow down the rate of the ion homeostasis disturbance and, as a con-sequence, reduce the chill injury and delay the occur-rence of prefreeze mortality [11]

Fig 2 Polyol and sugar body contents in the adult beetle A diaperinus kept at con-stant 20 C (control), and fluctuating thermal regimes (20 C ⁄ 12 h: 20 C F0 , and

0 C ⁄ 12 h: 0 C F20 ).Values are mean ± SE (n ¼ 6) Bars with different letters indicate significant differences between FAA (P < 0.05).

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Cold exposure and associated metabolic changes

Generally, cold stress is associated with an increase in

the levels of several FAA during the first days in most

species tested to date, resulting in an increase of the

total FAA pool [13,19] Even though no significant

increase of the FAA pool was recorded in 7-day

cold-exposed beetles, our results demonstrate that protein

catabolism occurred: five essential amino acids, Lys,

Iso, Leu, Phe and Trp, were accumulated Even if

interconversions and other metabolic alterations may

occur, it was demonstrated that removal of one of

each of the essential amino acids quickly resulted in

the death of the insects [29] For instance, Tenebrionid

species supplied with a Lys- and Trp-deficient diet

were incapable to sustain growth unless it was

supple-mented with both amino acids [30] The significant

accumulation of Lys, but also Iso, Leu and Trp found

in this study, and the inability to synthesize most

essential amino acids thus supports the conclusion that

it results from the breakdown of proteins

Under FTRs, the FAA pool was significantly

reduced during warm recovery periods Indeed, energy

supplies depleted during cold exposure, as observed in

A diaperinus [12], can be regenerated during the pulse

of high temperature [31] Recent proteomic data

dem-onstrated that several proteins involved in energy

pro-duction⁄ conversion are up-regulated under FTRs

(L Lalouette, H Colinet, D Siaussat & D Renault,

unpublished data) Moreover, it has been shown in

many insects that the HSP transcripts are up-regulated

during recovery from cold shock [32], and it was

recently found that FTRs significantly increase the

expression level of HSPs [17] HSPs are synthesized

during the pulses at high temperature, consuming the

FAA pool This assumption is supported by recent

proteomic studies showing significant up-regulations

of HSPs under FTRs (L Lalouette, H Colinet,

D Siaussat & D Renault, unpublished data)

As previously shown in several other insect species,

Pro was detected in remarkably high concentrations

Causal relationships between increased proline levels

and stress tolerance were also investigated, and a

posit-ive correlation was found with the insects’ cold

accli-mation [19], i.e Pro may stabilize either membranes or

proteins [3] However, the significant decrease of Pro

amounts recorded in cold-exposed beetles demonstrates

a reduced role of this amino acid in A diaperinus cold

acclimation Pro is an important energy substrate to

maintain ATP levels [4]: the energy yield from partial

oxidation of Pro to Ala is only slightly lower in

com-parison with lipids [33] A large accumulation of Ala

that occurred after the insects were cold exposed

(0Cc and 0CF20), which prompted a search for potential sources of the amino group, is thus an inter-esting result A partial involvement of the fermentative glycolysis in cold-exposed beetles, which would have led to increased amounts of Ala, was excluded Indeed, lactate was not detected in either these beetles or the

0CF20ones (data not presented) Moreover, a partial reliance on anaerobiosis would have resulted in a quicker depletion of glucose and glycogen amounts, because this type of respiration is less efficient in gen-erating ATP [15]

Ala accumulation suggests that it is derived from the singularly large stores of free Pro In that process, Pro is first oxidized to d-pyrolline-5-carboxylate which,

in turn, can be oxidized to Glu Transamination gave rise to Ala and a-ketoglutarate Such an increase in Ala contents is necessary to shuttle the amino group derived from the conversion of Pro to alpha-Ketoglu-tarate (a-KG) in flight muscle back to body fat [34] Oxidation of the keto acid in the citric acid cycle pro-duces ATP and results in the formation of malate, which is first converted to pyruvate and then to Ala When adult A diaperinus were warm exposed, Ala was reconverted back to pyruvate in the muscle, which is then a source of carbon atoms for gluconeogenesis This result is supported by the significantly higher amount of glucose found in 20CF0 beetles More-over, Pro is a well-known precursor in glucose and gly-cogen de novo synthesis [4] The present reduced level

of Pro in 20CF0beetles and the concomitant increase

of glucose indicates a use of Pro for glucose synthesis during daily warmer periods

Gln is of interest because it has been shown to play

an important role in several physiological processes During cold exposures, proteins and amino acids can serve as an important energy source via conversion to Krebs’ cycle intermediates and subsequent oxidation to

CO2 However, an important by-product of amino acid oxidation is ammonia (here we use ammonia to refer

to both NH3 and NH4+, or a combination of the two) Ammonia can be fixed on Glu to yield Gln, which accumulates in large amounts in cold-exposed beetles A diaperinus can then utilize the nitrogen of the amide group of two Gln molecules to synthesize one uric acid molecule Indeed, most terrestrial insects are uricotelic animals (i.e they excrete uric acid), and the synthesis of Gln as a chemical compound to hide the free ammonia for posterior excretion by glutami-nase activity is the strategy used by several insects [34] Hazel et al [35] also showed that Gln levels can modulate the secretion of ions and water by isolated Malpighian tubules of Rhodnius prolixus (Hemiptera: Reduviidae) and Drosophila melanogaster (Diptera:

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Drosophilidae) Secreted fluid pH and Na+

concentra-tion increase and K+ concentration decreases in

response to Gln These findings are interesting, as Gln

levels were significantly lower in 0CF20 beetles, and

we previously demonstrated in A diaperinus that the

extracellular concentrations of potassium ions

increased during cold periods Potassium ion

concen-trations returned to normal during the pulse at high

temperature under FTRs [11]

Adult insects of different species usually respond to

environmental stresses, e.g exposure to low

tempera-tures, with a neurohormonal stress reaction involving

the metabolism of juvenile hormone, dopamine (DA),

octopamine (OA) and ecdysteroids [20,36] Tyr plays

an important role in that process, as a precursor of

several stress hormones in insects (including DA, OA

and tyramine [15,20]) It was demonstrated in

Drosophila species that heat exposures induce a rise in

the DA level [37] and a concomitant decrease of Tyr

amounts Thus, the reduced level of Tyr recorded in

stressed adults of A diaperinus might be related to an

increased hormone synthesis, like DA This hypothesis

must be tested in further studies

Other than amino acids, the importance of polyols

and sugars such as glycerol and trehalose has been

emphasized regularly during insect cold acclimation

[21] Glycerol and trehalose are usually highly

signifi-cantly accumulated during cold exposures, and have

been shown to play an important role in protecting

protein and membrane integrity during exposures to

various environmental stresses [3] However, no

signifi-cant accumulation of trehalose was observed in

cold-exposed adults of A diaperinus Trehalose that can be

converted back to glycogen may therefore relate to

energy storage functions Moreover, the decrease in

glucose levels revealed that both trehalose and glucose

are involved in the synthesis of glycerol when adults of

A diaperinus are subjected to cold stress Because a

direct correlation between the accumulation of polyols

and an increase of Lt50 in the bug P apterus has

already been observed [21], the distinct pattern

recor-ded for glycerol between constant cold exposure and

FTR may contribute to extended survival times in the

cold-exposed insects under FTR

The slight, but nonsignificant, accumulation of the

other polyols (myo-inositol, ribitol and sorbitol), and

the synthesis of arabinitol in cold-exposed beetles may

be related to their cold acclimation [18] Indeed,

relat-ively low concentrations of sugars and polyols (with

negligible colligative effects) are sufficient to enhance

survival at subzero temperatures Accumulation of

myo-inositol has been documented in a few species of

arthropods [38] In Harmonia axyridis (Coleoptera:

Coccinellidae), large amount of myo-inositol are accu-mulated during winter Its content synchronizes sea-sonally with supercooling capacity, lower lethal temperature and chilling tolerance [39], suggesting that myo-inositol may play some role in the control of cold tolerance in this beetle In Aulacophora nigripennis (Coleoptera: Chrysomelidae), a high level of chill toler-ance occurs only when myo-inositol is accumulated [40] Our data revealed changes in several specific metab-olites that are likely to be related to the thermal stress

We found that breakdown of proteins occurred within the first days of cold exposure The synthesis of Gln,

an amino acid than can hide the free ammonia for posterior excretion, and the reduced FAA pool found

in ‘warm-exposed’ beetles during FTRs, demonstrate that FAA serves as an important energy source More-over, protein synthesis, like HSPs (L Lalouette,

H Colinet, D Siaussat & D Renault, unpublished data), occurred during the warm recovery periods, con-suming the FAA pool Some FAAs have been shown

to have cryoprotective properties in insects [3], but the relationship between FAAs, cold tolerance and survival has not yet been well defined Instead of considering FAA only as a part of the osmo- and cryoprotective arsenal, they should also be regarded as main actors involved in the multiple regulatory pathways activated during cold acclimation [41] In conclusion, FTRs trig-ger the initiation of a metabolic response involving the synthesis of protective compounds such as polyols and HSPs that probably contribute to the increased dur-ation of survival in A diaperinus

Experimental procedures

Rearing and acclimation conditions

Adult A diaperinus (Coleoptera: Tenebrionidae) were origin-ally collected from poultry house litter at Mohon (Morbi-han, France, 231¢56 W, 483¢14 N; altitude: 60 m) in February 2005 The insects were then reared in darkness at

20C and supplied with water and food ad libitum, consist-ing of moistened bran and dry dog food All the insects used for this study were between 2 and 3 months old at the begin-ning of the experiment Adult beetles were then used ran-domly, either for survival experiments or biochemical assays

To investigate the duration of survival, and changes in amino acid, polyol and sugar levels, beetles were kept either

at constant or cycling low temperatures In all experiments, beetles were maintained in the darkness and supplied with water but without food It has previously been observed that beetles enter in chill-coma and are thus not able to feed [9,12] A short starvation period has a minor impact

on the survival and biochemistry of the beetles [24]

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The survival of A diaperinus has already been investigated

and discussed in previous studies [9,24], where the same

population of insects was subjected to similar constant

tem-peratures and FTRs In the present work, longer recovery

periods were used during FTRs, in order to obtain

contras-ted metabolic responses between cold- (chilled) and

warm-exposed beetles

Groups of 10 beetles were transferred to Petri dishes To

avoid potential cold-shock, the insects were exposed at

15C for 48 h before being used for the survival

experi-ments Batches of beetles were randomly assigned to each

one of the following two thermal treatments (Fig 3): (a)

Constant low temperature: 10 Petri dishes were kept at

0C; and (b) fluctuating thermal regime: the beetles were

exposed 12 h at 20C cycling with 12 h at 0 C (n ¼ 10

Petri dishes) The cycling temperature regime started at

20C

One Petri dish per treatment was removed at daily

inter-vals, and the survival was assessed as the number of beetles

that showed limb movement after 2 days of recovery at

25C

Metabolite analysis

Groups of 50 beetles were placed in Petri dishes Two series

of experiments were performed as follows (Fig 3): (a)

Con-stant low temperature: three Petri dishes were kept at 0C

(0Cc), and the Petri dishes were removed from the

incuba-tor after 7 days; and (b) fluctuating thermal regime: beetles

were exposed 12 h at 20C interrupted by a daily transfer

to 0C for 12 h The cycling temperature regime started at

20C Two Petri dishes were removed from the incubators

after 7 days The first Petri dish was removed at the end of

the 12 h)20 C cycle, just before the temperature started

dropping to 0C (20 CF0) The second Petri dish was

removed 12 h later at the end of the 12 h)0 C cycle, just

before the temperature started rising to 20C (0 CF20)

Once removed, the insects were immediately pooled (n¼

3 per sample) and weighed (FM) using a Mettler

micro-balance accurate to 0.01 mg The beetles were then frozen

in liquid nitrogen and then stored at )80 C until the amino acid assays were performed Metabolites were also analyzed in control beetles reared at 20C in darkness; food was removed 2 days before sampling the insects as described in previous studies [12,13] For each experimental condition, 6–8 samples were analyzed

Amino acids

Amino acids were extracted from fresh material as des-cribed by Renault et al [13] Groups of three animals were homogenized in 1.5 mL of 70% ethanol and Fontainebleau sand, before adding 1.5 mL of 40% ethanol The homogen-ate was centrifuged for 10 min at 4500 g and 4C (Sigma 2-16 K, angle rotor 10· 20, Sigma-Aldrich Co.), and the supernatant collected The first pellet was re-suspended in 1.5 mL of 70% ethanol and centrifuged for 10 min at

4500 g and 4C (Sigma 2-16 K, angle rotor 10 · 20, Sigma-Aldrich Co.), and the supernatant collected The sec-ond pellet was re-suspended in 1.5 mL ultrapure water and centrifuged for 10 min at 4500 g and 4C (Sigma 2-16 K, angle rotor 10· 20, Sigma-Aldrich Co.) The combined supernatant (n¼ 3) was pooled in a balloon flask and dried

by evaporation using a rota-vapour system The insoluble residue was re-suspended in 1 mL of ultrapure water Free amino acids were assayed as described by Bouche-reau et al [25] Amino acids were characterized and quanti-fied by HPLC after precolumn derivatization with 6-aminoquinolyl-N-hydroxysuccinimidylcarbamate (using a Waters Accq-Tag amino acid analysis system; Waters Cor-poration, Milford, MA, USA) and reversed-phase liquid chromatographic separation (see [25] for a full description

of the method) Aliquots (10 lL) of the crude aqueous extracts were assayed using the procedure optimized by Bouchereau et al [25]

Sugars and polyols

Once removed from the incubator, the weighed beetles (n¼ 1 per sample) were homogenized with 0.4 mL of 70% (v⁄ v) ethanol The concentration of polyols was measured

by capillary gas chromatography (Varian 3400, Palo Alto,

Fig 3 Experimental design of the protocol used to determine the impact of cold exposure and associated metabolic changes in adults of

A diaperinus Batches of beetles were exposed at constant low temperature (0 C c ) and fluctuating thermal regime (20 C ⁄ 12 h: 20 C F0 , alternating with 0 C ⁄ 12 h: 0 C F20 ).

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CA, USA) as their o-methyloxime trimethysilyl derivates.

Identity of revealed component was established against

authentic standards and by mass spectrometry (Kratos,

Manchester, UK) The protocol was fully described earlier

by Kosˇta´l & Simek [5]

Statistical analyses

Values are given as the means ± se Lethal times for 50%

of the population (Lt50) were computed using probit

analy-sis for each temperature ancovas were performed to

remove the effects of body size Tukey’s tests were used for

post hoccomparisons The data were logarithmically

trans-formed, which improved their fit to a normal distribution

When the data did not follow normal distribution,

nonpar-ametric tests (Mann–Whitney: median comparison) were

conducted These statistical analyses were performed using

minitabTM (version 13) for Windows (Minitab Inc, 2000,

Paris, France)

Acknowledgements

This paper is publication number BRC 111 of the

Bio-diversity Research Centre of the Universite´ Catholique

de Louvain

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