Unravelling the determinants of human health in French Polynesia: the MATAEA project.

Background: French Polynesia is a French overseas collectivity in the Southeast Pacific, comprising 75 inhabited islands across five archipelagoes. The human settlement of the region corresponds to the last massive migration of humans to empty territories, but its timeline is still debated. Despite their recent population history and geographical isolation, inhabitants of French Polynesia experience health issues similar to those of continental countries. Modern lifestyles and increased longevity have led to a rise in non-communicable diseases (NCDs) such as obesity, diabetes, hypertension, and cardiovascular diseases. Likewise, international trade and people mobility have caused the emergence of communicable diseases (CDs) including mosquito-borne and respiratory diseases. Additionally, chronic pathologies including acute rheumatic fever, liver diseases, and ciguatera, are highly prevalent in French Polynesia. However, data on such diseases are scarce and not representative of the geographic fragmentation of the population. Objectives: The present project aims to estimate the prevalence of several NCDs and CDs in the population of the five archipelagoes, and identify associated risk factors. Moreover, genetic analyses will contribute to determine the sequence and timings of the peopling history of French Polynesia, and identify causal links between past genetic adaptation to island environments, and present-day susceptibility to certain diseases. Methods: This cross-sectional survey is based on the random selection of 2,100 adults aged 18-69 years and residing on 18 islands from the five archipelagoes. Each participant answered a questionnaire on a wide range of topics (including demographic characteristics, lifestyle habits and medical history), underwent physical measurements (height, weight, waist circumference, arterial pressure, and skin pigmentation), and provided biological samples (blood, saliva, and stool) for biological, genetic and microbiological analyses. Conclusion: For the first time in French Polynesia, the present project allows to collect a wide range of data to explore the existence of indicators and/or risk factors for multiple pathologies of public health concern. The results will help health authorities to adapt actions and preventive measures aimed at reducing the incidence of NCDs and CDs. Moreover, the new genomic data generated in this study, combined with anthropological data, will increase our understanding of the peopling history of French Polynesia. Clinical trial registration: https://clinicaltrials.gov/, identifier: NCT06133400.

Branched-Chain and Aromatic Amino Acids in Relation to Fat Mass and Fat-Free Mass Changes among Adolescents: A School-Based Intervention.

Plasma levels of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) are considered early metabolic markers of obesity and insulin resistance (IR). This study aimed to assess changes in plasma concentrations of BCAA/AAA and HOMA-IR2 (homeostasis model assessment of IR) after intervention-induced modifications in fat mass (FM) and fat-free mass (FFM) among French Polynesian adolescents. FM, FFM, plasma levels of BCAA and AAA, HOMA-IR2 were recorded at baseline and post intervention among 226 adolescents during a 5-month school-based intervention on diet and physical activity. Participants were divided into two subgroups according to their college attendance status which determined their intervention adherence: externs/half-residents (n = 157) and residents (n = 69). Four ordinal categories of body composition changes post-intervention were created for the analysis (FMgain/FFMlost < FMgain/FFMgain < FMlost/FFMlost < FMlost/FFMgain). After 5 months, changes in BCAA (p−trend < 0.001) and AAA (p−trend = 0.007) concentrations were positively associated with ordinal categories of body composition. HOMA-IR2 significantly decreased with FMlost (−0.40; 95% CI, −0.60 to −0.20) and increased with FMgain (0.23; 95% CI, 0.11 to 0.36). Our results suggest that FM loss is associated with a decrease in concentrations of obesity and IR metabolic markers which is more substantial when FM loss is accompanied with FFM gain.

Tetrodotoxin Poisoning in Mainland France and French Overseas Territories: A Review of Published and Unpublished Cases.

Tetrodotoxin is one of the most potent neurotoxins in the aquatic world. This review of published and unpublished reports aims to describe the poisoning cases that have occurred in mainland France and overseas territories. Six articles were included, with 13 poisoning events, individuals or collective (number (n) = 53 patients). Moreover, 13 unpublished poisoning events from toxicovigilance networks were found (n = 17). All cases happened in overseas territories: French Guyana (n = 7), New Caledonia (n = 11), Reunion (n = 35) and French Polynesia (n = 17). The median age was 36 years. The most frequent signs were neurological (81.8%), digestive (54.5%) and general (52.3%). Three cases of dysgueusia and nine cases of urogenital discomfort were observed in French Polynesia. Twelve severe cases were reported, including seven deaths. Only three events (11.5%) were documented by a tetrodotoxin assay. Two families of fish accounted for 91.6% of the poisonings: 33.3% due to the Diodontidae family and 58.3% to the Tetraodontidae family. Although rare, information and collection campaigns on tetrodotoxin poisoning are, therefore, essential.

A systematic prioritization approach for identifying suitable pearl oyster restocking zones following a mass mortality event in Takaroa Atoll, French Polynesia.

Oyster farming for black pearl production is central in French Polynesia. It is the second source of national income and provides substantial job opportunities, notably in remote atolls. However, this sector has been undermined by successive crises, such as mass-mortalities of wild and farmed oyster stocks that have impacted entire lagoons. An option to revive the activity consists of reintroducing oysters in strategic benthic locations selected to maximize reproduction and dispersal of larvae throughout the lagoon, hence promoting recolonization and spat collection for farming. For Takaroa, a Tuamotu atoll recently impacted by mortalities, a systematic prioritization approach identified these restocking sites, using environmental and socio-economic criteria such as: location of suitable habitats for oyster settlement, larval connectivity estimated from hydrodynamic circulation model, farming waste accumulation, and opportunity cost to fishers and farmers who lose access to restocking areas. This approach provides managers with a portfolio of restocking options.

Deep-Water Fish Are Potential Vectors of Ciguatera Poisoning in the Gambier Islands, French Polynesia.

Ciguatera poisoning (CP) cases linked to the consumption of deep-water fish occurred in 2003 in the Gambier Islands (French Polynesia). In 2004, on the request of two local fishermen, the presence of ciguatoxins (CTXs) was examined in part of their fish catches, i.e., 22 specimens representing five deep-water fish species. Using the radioactive receptor binding assay (rRBA) and mouse bioassay (MBA), significant CTX levels were detected in seven deep-water specimens in Lutjanidae, Serranidae, and Bramidae families. Following additional purification steps on the remaining liposoluble fractions for 13 of these samples (kept at -20 °C), these latter were reanalyzed in 2018 with improved protocols of the neuroblastoma cell-based assay (CBA-N2a) and liquid chromatography tandem mass spectrometry (LC-MS/MS). Using the CBA-N2a, the highest CTX-like content found in a specimen of Eumegistus illustris (Bramidae) was 2.94 ± 0.27 µg CTX1B eq. kg-1. Its toxin profile consisted of 52-epi-54-deoxyCTX1B, CTX1B, and 54-deoxyCTX1B, as assessed by LC-MS/MS. This is the first study demonstrating that deep-water fish are potential ciguatera vectors and highlighting the importance of a systematic monitoring of CTXs in all exploited fish species, especially in ciguatera hotspots, including deep-water fish, which constitute a significant portion of the commercial deep-sea fisheries in many Asian-Pacific countries.

Screening for Predictors of Chronic Ciguatera Poisoning: An Exploratory Analysis among Hospitalized Cases from French Polynesia.

Ciguatera poisoning is a globally occurring seafood disease caused by the ingestion of marine products contaminated with dinoflagellate produced neurotoxins. Persistent forms of ciguatera, which prove to be highly debilitating, are poorly studied and represent a significant medical issue. The present study aims to better understand chronic ciguatera manifestations and identify potential predictive factors for their duration. Medical files of 49 patients were analyzed, and the post-hospitalization evolution of the disease assessed through a follow-up questionnaire. A rigorous logistic lasso regression model was applied to select significant predictors from a list of 37 patient characteristics potentially predictive of having chronic symptoms. Missing data were handled by complete case analysis, and a survival analysis was implemented. All models used standardized variables, and multiple comparisons in the survival analyses were handled by Bonferroni correction. Among all studied variables, five significant predictors of having symptoms lasting ≥3 months were identified: age, tobacco consumption, acute bradycardia, laboratory measures of urea, and neutrophils. This exploratory, hypothesis-generating study contributes to the development of ciguatera epidemiology by narrowing the list from 37 possible predictors to a list of five predictors that seem worth further investigation as candidate risk factors in more targeted studies of ciguatera symptom duration.

Evidence for the Range Expansion of Ciguatera in French Polynesia: A Revisit of the 2009 Mass-Poisoning Outbreak in Rapa Island (Australes Archipelago).

Ciguatera poisoning (CP) results from the consumption of seafood contaminated with ciguatoxins (CTXs). This disease is highly prevalent in French Polynesia with several well-identified hotspots. Rapa Island, the southernmost inhabited island in the country, was reportedly free of CP until 2007. This study describes the integrated approach used to investigate the etiology of a fatal mass-poisoning outbreak that occurred in Rapa in 2009. Symptoms reported in patients were evocative of ciguatera. Several Gambierdiscus field samples collected from benthic assemblages tested positive by the receptor binding assay (RBA). Additionally, the toxicity screening of ≈250 fish by RBA indicated ≈78% of fish could contain CTXs. The presence of CTXs in fish was confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS). The potential link between climate change and this range expansion of ciguatera to a subtropical locale of French Polynesia was also examined based on the analysis of temperature time-series data. Results are indicative of a global warming trend in Rapa area. A five-fold reduction in incidence rates was observed between 2009 and 2012, which was due in part to self-regulating behavior among individuals (avoidance of particular fish species and areas). Such observations underscore the prominent role played by community outreach in ciguatera risk management.

Taxonomy and toxicity of a bloom-forming Ostreopsis species (Dinophyceae, Gonyaulacales) in Tahiti island (South Pacific Ocean): one step further towards resolving the identity of O. siamensis.

Among dinoflagellates responsible for benthic harmful algal blooms, the genus Ostreopsis primarily described from tropical areas has been increasingly reported from subtropical and temperate areas worldwide. Several species of this toxigenic genus produce analogs of palytoxin, thus representing a major threat to human and environmental health. The taxonomy of several species needs to be clarified as it was based mostly on morphological descriptions leading in some cases to ambiguous interpretations and misidentifications. The present study aims at reporting a benthic bloom that occurred in April 2019 in Tahiti island, French Polynesia. A complete taxonomic investigation of the blooming Ostreopsis species was realized using light, epifluorescence and field emission electron microscopy and phylogenetic analyses inferred from LSU rDNA and ITS-5.8S rDNA regions. Toxicity of a natural sample and strains isolated from the bloom was assessed using both neuroblastoma cell-based assay and LC-MS/MS analyses. Morphological observations showed that cells were round to oval, large, 58.0-82.5 µm deep (dorso-ventral length) and 45.7-61.2 µm wide. The cingulum was conspicuously undulated, forming a 'V' in ventral view. Thecal plates possessed large pores in depressions, with a collar rim. Detailed observation also revealed the presence of small thecal pores invisible in LM. Phylogenetic analyses were congruent and all sequences clustered within the genotype Ostreopsis sp. 6, in a subclade closely related to sequences from the Gulf of Thailand and Malaysia. No toxicity was found on the field sample but all the strains isolated from the bloom were found to be cytotoxic and produced ostreocin D, a lower amount of ostreocins A and B and putatively other compounds. Phylogenetic data demonstrate the presence of this species in the Gulf of Thailand, at the type locality of O. siamensis, and morphological data are congruent with the original description and support this identification.

Modeling the time-lag effect of sea surface temperatures on ciguatera poisoning in the South Pacific: Implications for surveillance and response.

Ciguatera poisoning (CP), arising from ciguatoxins produced by toxic dinoflagellate Gambierdiscus, is one of the most common food-borne diseases in the South Pacific. Climate change as well as its related events have been hypothesized to a higher abundance and wider presence of toxic dinoflagellates, hence a higher risk of the disease. Yet existing studies assessing the relationship between climate factors and CP are limited or based on old data. In this study, we used prewhitened cross-correlation analysis and auto-regressive integrated moving-average (ARIMA) modeling to develop predictive models of monthly CP incidence in Cook Islands and French Polynesia, two ciguatera-endemic regions in the South Pacific, utilizing the latest epidemiological data. Results reveal the significant time-lagged associations between the monthly CP incidence rate and several indicators relating to sea surface temperature (SST). In particular, SST anomaly is proven to be a strong positive predictor of an increased ciguatera incidence for both countries. If these time-lags can be supported by more investigations, it will allow health authorities to take appropriate actions, to limit or avoid an epidemic risk, especially on high-risk climate scenarios.

Ostreopsis lenticularis Y. Fukuyo (Dinophyceae, Gonyaulacales) from French Polynesia (South Pacific Ocean): A revisit of its morphology, molecular phylogeny and toxicity.

To date, the genus Ostreopsis comprises eleven described species, of which seven are toxigenic and produce various compounds presenting a major threat to human and environmental health. The taxonomy of several of these species however remains controversial, as it was based mostly on morphological descriptions leading, in some cases, to ambiguous interpretations and even possible misidentifications. The species Ostreopsis lenticularis was first described by Y. Fukuyo from French Polynesia using light microscopy observations, but without genetic information associated. The present study aims at revisiting the morphology, molecular phylogeny and toxicity of O. lenticularis based on the analysis of 47 strains isolated from 4 distinct locales of French Polynesia, namely the Society, Australes, Marquesas and Gambier archipelagos. Observations in light, epifluorescence and field emission scanning electron microscopy of several of these strains analyzed revealed morphological features in perfect agreement with the original description of O. lenticularis. Cells were oval, not undulated, 60.5-94.4 µm in dorso-ventral length, 56.1-78.2 µm in width, and possessed a typical plate pattern with thecal plates showing two sizes of pores. Phylogenetic analyses inferred from the LSU rDNA and ITS-5.8S sequences revealed that the 47 strains correspond to a single genotype, clustering with a strong support with sequences previously ascribed to Ostreopsis sp. 5. Clonal cultures of O. lenticularis were also established and further tested for their toxicity using the neuroblastoma cell-based assay and LCMS/MS analyses. None of the 19 strains tested showed toxic activity on neuroblastoma cells, while LCMS/MS analyses performed on the strains from Tahiti Island (i.e. type locality) confirmed that palytoxin and related structural analogs were below the detection limit. These findings allow to clarify unambiguously the genetic identity of O. lenticularis while confirming previous results from the Western Pacific which indicate that this species shows no toxicity, thus stressing the need to reconsider its current classification within the group of toxic species.

Toxicological Investigations on the Sea Urchin Tripneustes gratilla (Toxopneustidae, Echinoid) from Anaho Bay (Nuku Hiva, French Polynesia): Evidence for the Presence of Pacific Ciguatoxins.

The sea urchin Tripneustes gratilla (Toxopneustidae, Echinoids) is a source of protein for many islanders in the Indo-West Pacific. It was previously reported to occasionally cause ciguatera-like poisoning; however, the exact nature of the causative agent was not confirmed. In April and July 2015, ciguatera poisonings were reported following the consumption of T.gratilla in Anaho Bay (Nuku Hiva Island, Marquesas archipelago, French Polynesia). Patient symptomatology was recorded and sea urchin samples were collected from Anaho Bay in July 2015 and November 2016. Toxicity analysis using the neuroblastoma cell-based assay (CBA-N2a) detected the presence of ciguatoxins (CTXs) in T.gratilla samples. Gambierdiscus species were predominant in the benthic assemblages of Anaho Bay, and G.polynesiensis was highly prevalent in in vitro cultures according to qPCR results. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses revealed that P-CTX-3B was the major ciguatoxin congener in toxic sea urchin samples, followed by 51-OH-P-CTX-3C, P-CTX-3C, P-CTX-4A, and P-CTX-4B. Between July 2015 and November 2016, the toxin content in T.gratilla decreased, but was consistently above the safety limit allowed for human consumption. This study provides evidence of CTX bioaccumulation in T.gratilla as a cause of ciguatera-like poisoning associated with a documented symptomatology.

Tectus niloticus (Tegulidae, Gastropod) as a Novel Vector of Ciguatera Poisoning: Clinical Characterization and Follow-Up of a Mass Poisoning Event in Nuku Hiva Island (French Polynesia).

Ciguatera fish poisoning (CFP) is the most prevalent non-bacterial food-borne form of poisoning in French Polynesia, which results from the consumption of coral reef fish naturally contaminated with ciguatoxins produced by dinoflagellates in the genus Gambierdiscus. Since the early 2000s, this French territory has also witnessed the emergence of atypical forms of ciguatera, known as ciguatera shellfish poisoning (CSP), associated with the consumption of marine invertebrates. In June 2014, nine tourists simultaneously developed a major and persistent poisoning syndrome following the consumption of the gastropod Tectus niloticus collected in Anaho, a secluded bay of Nuku Hiva Island (Marquesas Archipelago, French Polynesia). The unusual nature and severity of this event prompted a multidisciplinary investigation in order to characterize the etiology and document the short/long-term health consequences of this mass-poisoning event. This paper presents the results of clinical investigations based on hospital medical records, medical follow-up conducted six and 20 months post-poisoning, including a case description. This study is the first to describe the medical signature of T. niloticus poisoning in French Polynesia and contributed to alerting local authorities about the potential health hazards associated with the consumption of this gastropod, which is highly prized by local communities in Pacific island countries and territories.

Application of solid phase adsorption toxin tracking (SPATT) devices for the field detection of Gambierdiscus toxins.

Ciguatera fish poisoning is a food-borne illness caused by the consumption of seafood contaminated with ciguatoxins (CTXs) produced by dinoflagellates in the Gambierdiscus genus. Since most surveillance programs currently rely on the survey of Gambierdiscus cell densities and species composition, supplementary toxin-based methods allowing the time- and spatially integrated sampling of toxins in ciguateric environments are needed for a more reliable assessment and management of the risks associated with Gambierdiscus proliferation. Solid Phase Adsorption Toxin Tracking (SPATT) filters use porous synthetic resins capable of adsorbing toxins directly from the water column. To assess the ability of these passive monitoring devices to retain Gambierdiscus toxins, SPATT bags filled with 10g of HP20 resin were deployed for 48h in two French Polynesian locations at high (Nuku Hiva Island) vs. low to moderate (Kaukura Atoll) risk of ciguatera. CTXs could be detected in SPATT bags extracts from Nuku Hiva Island, as assessed by the mouse neuroblastoma cell-based assay (CBA-N2a) and liquid chromatography - tandem mass spectrometry (LC-MS/MS) analyses. Results of in vitro experiments suggest that the saturation limit of CTXs on HP20 resin, for a deployment time of 48h, is ≃ 55ng P-CTX-3C equiv. g-1 resin. Despite the non detection of maitotoxin (MTX), LC-MS/MS analyses showed that two other compounds also produced by Gambierdiscus species were retained on SPATT bags, i.e. iso-P-CTX-3B/C and a putative MTX analogue, known as MTX-3. This study, the first to demonstrate the suitability of SPATT technology for the in situ monitoring of Gambierdiscus toxins, highlights the potential application of this tool for routine ciguatera risk assessment and management programs.

Tectus niloticus (Tegulidae, Gastropod) as a Novel Vector of Ciguatera Poisoning: Detection of Pacific Ciguatoxins in Toxic Samples from Nuku Hiva Island (French Polynesia).

Ciguatera fish poisoning (CFP) is a foodborne disease caused by the consumption of seafood (fish and marine invertebrates) contaminated with ciguatoxins (CTXs) produced by dinoflagellates in the genus Gambierdiscus. The report of a CFP-like mass-poisoning outbreak following the consumption of Tectus niloticus (Tegulidae, Gastropod) from Anaho Bay on Nuku Hiva Island (Marquesas archipelago, French Polynesia) prompted field investigations to assess the presence of CTXs in T. niloticus. Samples were collected from Anaho Bay, 1, 6 and 28 months after this poisoning outbreak, as well as in Taiohae and Taipivai bays. Toxicity analysis using the neuroblastoma cell-based assay (CBA-N2a) detected the presence of CTXs only in Anaho Bay T. niloticus samples. This is consistent with qPCR results on window screen samples indicating the presence of Gambierdiscus communities dominated by the species G. polynesiensis in Anaho Bay. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses revealed that P-CTX-3B was the major congener, followed by P-CTX-3C, P-CTX-4A and P-CTX-4B in toxic samples. Between July 2014 and November 2016, toxin content in T. niloticus progressively decreased, but was consistently above the safety limit recommended for human consumption. This study confirms for the first time T. niloticus as a novel vector of CFP in French Polynesia.

Ciguatera fish poisoning: Incidence, health costs and risk perception on Moorea Island (Society archipelago, French Polynesia).

Ciguatera Fish Poisoning (CFP) is a non-bacterial seafood poisoning well characterized in the remote archipelagos of French Polynesia, yet poorly documented in the Society archipelago, most notably on Moorea, the second most populated island in French Polynesia, which counts a high proportion of fishermen fishing on a regular basis. To address this knowledge gap, a holistic study of the ciguatera issue was conducted on Moorea. First, ciguatera risk was analysed in terms of incidence rate, fish species most commonly involved and risk stratification in Moorea lagoon based on 2007-2013 epidemiological data. A mean incidence rate of 8 cases per 10,000 inhabitants for the study period and an average under-reporting rate of 54% were found. Taking into account hospitalization and medication fees, and loss of productive days, the health-related costs due to CFP were estimated to be USD $1613 and $749 for each reported and unreported case, respectively, with an overall cost of USD $241,847 for the study period. Comparison of the present status of CFP on Moorea with a risk map established in the late 1970's showed that the spatial distribution of the risk has stayed relatively stable in time, with the north shore of the island remaining the most prone to ciguatera. Evaluation of the current knowledge on CFP among different populations groups, i.e. fishermen, residents and visitors, was also conducted through direct and indirect interviews. About half of the fishermen interviewed were actually able to identify risky fishing areas. While, overall, the CFP risk perception in the fishing community of Moorea seemed accurate, although not scientifically complete, it was sufficient for the safe practice of their fishing activities. This may be due in part to adaptive responses adopted by 36% of the fishermen interviewed, such as the avoidance of either high-risk fishing sites or toxic species. At the residents and visitors' level, the study points out a striking lack of awareness of the CFP issue among visitors, as compared to local residents. Indeed, less than 25% of Moorea visitors vs. an average of 98% in residents were aware of CFP or of its presence on the island. Interestingly, evaluation of the fish consumption preferences showed that 70% of visitors do not consume lagoon fish during their stay, not for fear of CFP, but mainly due to the lack of availability of these species in recreational facilities or because they have nutritional preference for pelagic fish. This lack of awareness, along with the report by several CFP patients of the consumption of fish species yet banned for sale, stress the need for improved communication efforts on this critical issue among both residents and visitors on Moorea. The implementation of a public outreach strategy is proposed, based on both existing information networks and low-cost communication actions through information displays at various strategic locations, e.g. Tahiti-Faa'a international airport, the ferry boat station, recreational facilities, as well as the major trading points on Moorea Island.

Obesity and metabolic parameters in adolescents: a school-based intervention program in French Polynesia.

PURPOSE: The prevalence of overweight/obesity among French Polynesian adolescents is alarming. This study aims to prevent rises in obesity by modifying school food and the physical environment of French Polynesian adolescents. METHODS: During the 5-month study, 240 adolescents from a Tubuai island college (in French Polynesia) received a balanced diet based almost exclusively on local agricultural products and fishing by the island community. They were divided into three subgroups according to their college attendance status: external (n = 14), half residents (n = 155), and residents (n = 71). To increase energy expenditure, weekly physical activity was augmented by 2-4 hours of training in Polynesian Va'a canoes. Anthropometric parameters were recorded, and blood samples collected at baseline and after 5 months. Collegians from Rurutu, a neighboring island, were considered as controls (N = 90). RESULTS: At baseline, overweight/obesity prevalence was 60% (with 28% obesity) in the intervention group. After 5 months, adjusted weight gain was -.76 kg for residents (95% confidence interval [CI], -1.59 to .08), 1.34 kg for half residents (95% CI, .84-1.83), 1.82 kg for externs (95% CI, .66-2.97), and 4.2 kg (95% CI, 3.4-5.0) in the controls. Our results indicate that the more adolescents were subjected to food and physical activity commitments, the higher was the rate among those who lost weight. We noted that the weight change magnitude predicted insulin, glucose, and visceral obesity modifications. CONCLUSIONS: This 5-month school-based intervention slowed weight gain and improved the health of Polynesian collegians. The implementation of longer school-based interventions deserves evaluation.

Tonic and phasic effects of corticosterone on food restriction-induced hyperactivity in rats.

In the experimental rat model of anorexia nervosa the interactions between the hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis and increased physical activity associated with food restriction remain unidentified. In addition to their role in energy homeostasis, glucocorticoids have complex effects in the central nervous system, increasing the salience of activities such as wheel running. The objective of the present study was to analyze the role of corticosterone (cort) on wheel activity in food-restricted rats. Lewis rats were adrenalectomized and replaced with pellets containing increasing amounts of cort that caused different steady-state plasma concentrations from low to high HPA activity. They were given free access to a running wheel and were fed ad libitum or food-restricted. We also investigated the acute effect of cort injection mimicking the prefeeding cort peak on prefeeding wheel activity. Wheel running induced by food restriction was nearly non-existent in adrenalectomized food-restricted rats and increased in a dose-related manner with cort replacement. An acute stimulation of activity was also expressed during the preprandial peak of cort, suppressed by adrenalectomy and experimentally restored by acute cort injection. No such effects of cort were found in ad libitum fed rats. Our data demonstrate that food restriction-induced hyperactivity is critically and quantitatively dependent upon cort, not only on the mean basal levels of the hormone but also on the secretory peak that accompanies the burst of preprandial activity. The present results have special relevance for the pathophysiology of anorexia nervosa and other compulsive behaviors.