O câncer de mama permanece como segundo tipo de câncer mais frequente no mundo e o primeiro entre as mulheres. Tumores de mama podem ser categorizados pela expressão de receptores como o HER-2 (receptor de fator de crescimento epidermal 2). A hiperexpressão do receptor HER-2 é observada em cerca de 30% dos carcinomas de mama, e está associada a prognósticos desfavoráveis. Os ácidos graxos poli-insaturados (AGPI) , como os ácidos graxos ômega-3, parecem diminuir o risco de câncer de mama. O ácido docosahexaenoico (DHA), um tipo de AGPI ômega-3 parece ter o maior potencial antitumoral no câncer de mama. Alguns mecanismos de ação foram propostos para a ação do DHA no controle do câncer de mama, no entanto, faltam dados para elucidar os mecanismos moleculares do DHA no tecido mamário normal e cancerígeno. Dessa maneira, o objetivo desse trabalho foi avaliar a ação do DHA na modulação da expressão de genes em linhagem celular normal (HB4a), transformada (HB4aC5.2) e de carcinoma mamário humano (SKBR-3). As linhagens estudadas foram tratadas com 100 ?M de DHA ou controle (etanol) durante 72 horas. Após a extração de RNA realizamos a técnica de expressão gênica global (Microarray) para encontrar os genes diferencialmente expressos, em relação ao tratamento com DHA, em cada linhagem celular estudada. Na linhagem normal (HB4a) observamos 174 genes diferencialmente expressos (p<0,01), sendo 136 hiperexpressos e 38 hipoexpressos, na linhagem celular transformada (HB4aC5.2) encontramos 208 genes diferencialmente expressos (p<0,01), sendo 32 hiperexpressos e 176 hipoexpressos. A linhagem do carcinoma mamário (SKBR-3) apresentou 126 genes diferencialmente expressos (p<0,01), sendo 48 hiperexpressos e 78 hipoexpressos. A análise ontológica destes genes permitiu identificar processos biológicos como: adesão celular, diferenciação celular e metabolismo lipídico. Concluímos que o DHA altera o perfil de expressão gênica de maneiras distintas em linhagem normal, transformada e de carcinoma mamário humano. Além disso, encontramos após o tratamento com DHA genes envolvidos com o metabolismo lipídico nas linhagens que hiperexpressam o receptor HER-2 / Breast cancer remains the second most common cancer in the world and first among women. Breast tumors can be categorized by the expression of receptors such as HER-2. Overexpression of HER-2 receptor is associated with unfavorable prognosis.The polyunsaturated fatty acids (PUFAs) omega- 3 appears to decrease the risk of breast cancer. Docosahexaenoic acid (DHA), a type of omega-3 PUFAs, seems to have greater antitumor potential in breast cancer. However, the gene expression profile resulting from the action of DHA in breast cancer has not been elucidated yet. We aimed to examine the effects of DHA on normal breast cell line (HB4a), transformed cell line (HB4aC5.2) and breast cancer cell line (SKBR-3) and using a microarray approach. Cells were treated with 100?M of DHA for 72 hours. We identified 174, 208 and 126 differentially expressed genes after DHA treatment, in HB4a, HB4aC5.2 and SKBR3, respectively. Notably, the molecular pathways for the differentially expressed genes included those related to lipid metabolism, cell growth, molecular transport and cell-to-cell signaling. Where found genes related to overexpression of HER-2 after treatment with DHA. These genes involved in lipid metabolism and were down-expressed after treatment, suggesting a possible mechanism DHA in breast cancer by lipid metabolism control

Background: The adequacy of serum ascorbic acid (vitamin C) concentrations in young Canadian adults is unknown. Individuals have varied serum ascorbic acid response to dietary vitamin C, possibly due to genetic variation. Objective: To investigate the prevalence of serum ascorbic acid deficiency in young Canadians and to determine whether common genotypes modify the association between dietary vitamin C and serum ascorbic acid. Methods: Subjects were 1277 men and women aged 20-29 years from the Toronto Nutrigenomics and Health study. Vitamin C intakes were estimated by a 196-item FFQ. Fasting blood was collected to measure serum ascorbic acid by HPLC and to genotype for common polymorphisms in genes that code for glutathione S-transferase (GST) (GSTM1, GSTT1 and GSTP1), haptoglobin (Hp), and vitamin C transporters (SLC23A1 and SLC23A2). Results: 53% of subjects had adequate, 33% had suboptimal and 14% had deficient serum ascorbic acid. Subjects with deficiency had higher mean C-reactive protein, waist circumference, BMI and blood pressure than subjects with adequate serum ascorbic acid. The odds ratio (95% confidence interval) for serum ascorbic acid deficiency was 3.43 (2.14, 5.50) for subjects who did not meet the vitamin C recommendation compared to those who did. The corresponding odds ratios were 2.17 (1.10, 4.28) and 12.28 (4.26, 33.42) for individuals with the GSTT1 functional and null genotypes respectively (interaction p=0.01), and 2.29 (0.96, 5.45) and 4.03 (2.01, 8.09) for the GSTM1 functional and null genotypes (interaction p=0.04). These odds ratios were 4.77 (2.36, 9.65) for the Hp2-2 genotype, but 1.69 (0.80, 3.63) for carriers of the Hp1 allele (interaction p=0.02). Serum ascorbic acid concentrations (mean +/- SE) differed among SLC23A1 rs4257763 genotypes (GG: 24.4 +/- 1.3, GA: 26.8 +/- 1.1, AA: 29.7 +/- 1.4, p=0.002). Conclusions: Serum ascorbic acid deficiency is prevalent and associated with markers of chronic disease. Individuals with GST null or Hp2-2 genotypes had an increased risk of deficiency if they did not meet the recommendation for vitamin C, suggesting that GSTs and haptoglobin may spare ascorbic acid when dietary vitamin C is insufficient, thus protecting against serum ascorbic acid deficiency.

Background: The adequacy of serum ascorbic acid (vitamin C) concentrations in young Canadian adults is unknown. Individuals have varied serum ascorbic acid response to dietary vitamin C, possibly due to genetic variation. Objective: To investigate the prevalence of serum ascorbic acid deficiency in young Canadians and to determine whether common genotypes modify the association between dietary vitamin C and serum ascorbic acid. Methods: Subjects were 1277 men and women aged 20-29 years from the Toronto Nutrigenomics and Health study. Vitamin C intakes were estimated by a 196-item FFQ. Fasting blood was collected to measure serum ascorbic acid by HPLC and to genotype for common polymorphisms in genes that code for glutathione S-transferase (GST) (GSTM1, GSTT1 and GSTP1), haptoglobin (Hp), and vitamin C transporters (SLC23A1 and SLC23A2). Results: 53% of subjects had adequate, 33% had suboptimal and 14% had deficient serum ascorbic acid. Subjects with deficiency had higher mean C-reactive protein, waist circumference, BMI and blood pressure than subjects with adequate serum ascorbic acid. The odds ratio (95% confidence interval) for serum ascorbic acid deficiency was 3.43 (2.14, 5.50) for subjects who did not meet the vitamin C recommendation compared to those who did. The corresponding odds ratios were 2.17 (1.10, 4.28) and 12.28 (4.26, 33.42) for individuals with the GSTT1 functional and null genotypes respectively (interaction p=0.01), and 2.29 (0.96, 5.45) and 4.03 (2.01, 8.09) for the GSTM1 functional and null genotypes (interaction p=0.04). These odds ratios were 4.77 (2.36, 9.65) for the Hp2-2 genotype, but 1.69 (0.80, 3.63) for carriers of the Hp1 allele (interaction p=0.02). Serum ascorbic acid concentrations (mean +/- SE) differed among SLC23A1 rs4257763 genotypes (GG: 24.4 +/- 1.3, GA: 26.8 +/- 1.1, AA: 29.7 +/- 1.4, p=0.002). Conclusions: Serum ascorbic acid deficiency is prevalent and associated with markers of chronic disease. Individuals with GST null or Hp2-2 genotypes had an increased risk of deficiency if they did not meet the recommendation for vitamin C, suggesting that GSTs and haptoglobin may spare ascorbic acid when dietary vitamin C is insufficient, thus protecting against serum ascorbic acid deficiency.

alpha-tocopherol is the most abundant form of vitamin E in human plasma and tissues. Inter-individual differences in plasma alpha-tocopherol concentration or its response to dietary alpha-tocopherol may be due, in part, to polymorphisms in vitamin E metabolism genes (alpha-tocopherol transfer protein (alpha-TTP), tocopherol associated protein (TAP) and CYP4F2). The thesis objectives were to determine whether common polymorphisms in the alpha-TTP (rs6994076 A>T), TAP (rs2072157 C>T and Arg11Lys) and CYP4F2 (Val433Met) genes influence plasma alpha-tocopherol concentration or modify the association between dietary and plasma alpha-tocopherol. Subjects (n=1248), 20 to 29 years from the Toronto Nutrigenomics and Health study completed a food frequency questionnaire. Fasting blood samples were used for genotyping and to measure plasma alpha-tocopherol concentration. The alpha-TTP and TAP Arg11Lys polymorphisms significantly altered plasma alpha-tocopherol. The alpha-TTP polymorphism only influenced plasma alpha-tocopherol in individuals not using supplements. None of the polymorphisms examined modified the plasma alpha-tocopherol response to dietary alpha-tocopherol.

alpha-tocopherol is the most abundant form of vitamin E in human plasma and tissues. Inter-individual differences in plasma alpha-tocopherol concentration or its response to dietary alpha-tocopherol may be due, in part, to polymorphisms in vitamin E metabolism genes (alpha-tocopherol transfer protein (alpha-TTP), tocopherol associated protein (TAP) and CYP4F2). The thesis objectives were to determine whether common polymorphisms in the alpha-TTP (rs6994076 A>T), TAP (rs2072157 C>T and Arg11Lys) and CYP4F2 (Val433Met) genes influence plasma alpha-tocopherol concentration or modify the association between dietary and plasma alpha-tocopherol. Subjects (n=1248), 20 to 29 years from the Toronto Nutrigenomics and Health study completed a food frequency questionnaire. Fasting blood samples were used for genotyping and to measure plasma alpha-tocopherol concentration. The alpha-TTP and TAP Arg11Lys polymorphisms significantly altered plasma alpha-tocopherol. The alpha-TTP polymorphism only influenced plasma alpha-tocopherol in individuals not using supplements. None of the polymorphisms examined modified the plasma alpha-tocopherol response to dietary alpha-tocopherol.

Η παρούσα εργασία αποτελεί μια πρώτη προσπάθεια αξιολόγησης της απήχησης των υπηρεσιών Διατροφογονιδιωματικής στην Ελλάδα, που ακόμα είναι ελάχιστα αναπτυγμένες στην χώρα μας. Στόχος της είναι η κατανόηση των στάσεων και απόψεων του ελληνικού κοινού αναφορικά με τη σχέση γενετικής και διατροφής. Με τη μελέτη αυτή επιδιώκουμε επίσης να εκτιμήσουμε το επίπεδο γνώσεων και το ενδιαφέρον του ευρέος κοινού στους τομείς αυτούς και να σκιαγραφήσουμε τη διάθεσή τους να υποβληθούν σε γενετικές εξετάσεις με στόχο την συσχέτιση του γενετικού τους προφίλ με τη διατροφή τους και την ακόλουθη λήψη διαιτητικών συστάσεων. Για τους σκοπούς της έρευνας συντάχθηκε ένα Ερωτηματολόγιο με 16 ερωτήσεις κλειστού τύπου. Το δείγμα μας αποτέλεσαν 300 τυχαία επιλεγμένα άτομα στην πόλη της Πάτρας, που δέχτηκαν να απαντήσουν στο Ερωτηματολόγιο. Οι απαντήσεις μελετήθηκαν σε σχέση με το Φύλο, την Ηλικιακή Ομάδα και τον Δείκτη Σωματικού Βάρους των ερωτηθέντων, για να ελεγχθεί πιθανή επίδραση των παραγόντων αυτών στις απαντήσεις τους. Τα αποτελέσματά μας καταγράφουν ότι το ευρύ κοινό στην Ελλάδα εμφανίζεται να γνωρίζει τι είναι DNA και γενετικό υλικό καθώς και το ρόλο των γονιδίων στον καθορισμό της υγείας. Επίσης, φαίνεται να υπάρχει μια καλή θεώρηση της σχέσης μεταξύ διατροφής και υγείας. Υψηλό ποσοστό του κοινού εμφανίζονται ενήμεροι σχετικά με τα πιθανά οφέλη των γενετικών αναλύσεων, αν και το ποσοστό αυτό μειώνεται με την ηλικία. Τα δεδομένα μας έδειξαν ότι μόνο στο 9.7% από τους ερωτηθέντες έχει προταθεί να υποβληθούν σε μια γενετική εξέταση για τη σχέση γονιδίων και διατροφής, παρόλο που το 84% των συμμετεχόντων απάντησαν ότι θα ήταν διατεθειμένοι να το κάνουν. Ενδιαφέρον επίσης παρουσιάζει το γεγονός ότι η μεγάλη πλειοψηφία του κοινού προτιμά την παραπομπή ενός γιατρού για μια τέτοια εξέταση και πολύ λιγότερο τη συμβουλή ενός διατροφολόγου/διαιτολόγου. Συμπερασματικά, η μελέτη αυτή αποτελεί την πρώτη κριτική αξιολόγηση των απόψεων του ευρέος κοινού στην Ελλάδα όσον αφορά στις υπηρεσίες γενετικών εξετάσεων με στόχο συμβουλευτική διατροφής. Εφόσον δεν έχει διεξαχθεί άλλη τέτοια έρευνα, θεωρούμε ότι θα μπορούσε να χρησιμεύσει σαν πρότυπο για να μελετηθούν και άλλοι πληθυσμοί, και να στοχευθούν καλύτερα εκείνοι που: α) έχουν πραγματική ανάγκη τέτοιων αναλύσεων (πχ οικογενειακό ιστορικό παχυσαρκίας η καρδιαγγειακών νοσημάτων) και β) είναι επιστημονικά στοιχειωδώς ενήμεροι και φαίνονται διατεθειμένοι να υποβληθούν στις ανάλογες αναλύσεις (άρα έχουν εμπιστοσύνη στην αποτελεσματικότητά τους). / This research constitutes a first attempt to understand the general public’s knowledge concerning basic notions and services in genetics-based nutrition, as well as reveal their attitudes and perceptions on Nutrigenomics. With this research we also aspire to assess the level of knowledge an interest of the general public in this field and evaluate their willingness to undergo such genetic analyses, in order to correlate their genetic profile with their nutrition and receive dietary recommendations. For the purposes of this study, we designed a questionnaire of 16 questions and conducted a general public survey. Our sample consists of 300 participants, randomly chosen from the public, in the city of Patras in Greece. The answers were analyzed by grouping them according to Gender, Age group and the BMI of the participants, in order to check for potential influence of these factors on the answers. Our analysis indicated that the public in Patras appears quite knowledgeable concerning DNA and the role of the genome in determining overall health. Participants also have a good grasp of the relation of nutrition to health conditions. A large proportion of the general public is aware of the existence of gene-based disorders and the potential benefits of genetic testing, although this proportion declines steadily with age. Our data revealed that only 9.7% of respondents from the general public had been advised to take a genetic test in order to explore the relationship between their genes and their nutritional status. However, 84% of them would be willing to undergo nutrigenomic analysis to correlate their genetic profile with their diet. Interestingly, to do so, the vast majority of the general public would prefer referral from a physician than from a dietitian/nutritionist. Our study has provided the first critical evaluation of the views of the general public with regard to genetics and genetic testing services in Greece and, since no other such study has been conducted so far, it should serve as a model for replication in other populations, so that we could target the groups that a) are in need of such analyses due to family history of obesity or cardiovascular disease, and b) are fundamentally scientifically aware and seem willing to undergo such tests.

O câncer de mama permanece como segundo tipo de câncer mais frequente no mundo e o primeiro entre as mulheres. Tumores de mama podem ser categorizados pela expressão de receptores como o HER-2 (receptor de fator de crescimento epidermal 2). A hiperexpressão do receptor HER-2 é observada em cerca de 30% dos carcinomas de mama, e está associada a prognósticos desfavoráveis. Os ácidos graxos poli-insaturados (AGPI) , como os ácidos graxos ômega-3, parecem diminuir o risco de câncer de mama. O ácido docosahexaenoico (DHA), um tipo de AGPI ômega-3 parece ter o maior potencial antitumoral no câncer de mama. Alguns mecanismos de ação foram propostos para a ação do DHA no controle do câncer de mama, no entanto, faltam dados para elucidar os mecanismos moleculares do DHA no tecido mamário normal e cancerígeno. Dessa maneira, o objetivo desse trabalho foi avaliar a ação do DHA na modulação da expressão de genes em linhagem celular normal (HB4a), transformada (HB4aC5.2) e de carcinoma mamário humano (SKBR-3). As linhagens estudadas foram tratadas com 100 ?M de DHA ou controle (etanol) durante 72 horas. Após a extração de RNA realizamos a técnica de expressão gênica global (Microarray) para encontrar os genes diferencialmente expressos, em relação ao tratamento com DHA, em cada linhagem celular estudada. Na linhagem normal (HB4a) observamos 174 genes diferencialmente expressos (p<0,01), sendo 136 hiperexpressos e 38 hipoexpressos, na linhagem celular transformada (HB4aC5.2) encontramos 208 genes diferencialmente expressos (p<0,01), sendo 32 hiperexpressos e 176 hipoexpressos. A linhagem do carcinoma mamário (SKBR-3) apresentou 126 genes diferencialmente expressos (p<0,01), sendo 48 hiperexpressos e 78 hipoexpressos. A análise ontológica destes genes permitiu identificar processos biológicos como: adesão celular, diferenciação celular e metabolismo lipídico. Concluímos que o DHA altera o perfil de expressão gênica de maneiras distintas em linhagem normal, transformada e de carcinoma mamário humano. Além disso, encontramos após o tratamento com DHA genes envolvidos com o metabolismo lipídico nas linhagens que hiperexpressam o receptor HER-2 / Breast cancer remains the second most common cancer in the world and first among women. Breast tumors can be categorized by the expression of receptors such as HER-2. Overexpression of HER-2 receptor is associated with unfavorable prognosis.The polyunsaturated fatty acids (PUFAs) omega- 3 appears to decrease the risk of breast cancer. Docosahexaenoic acid (DHA), a type of omega-3 PUFAs, seems to have greater antitumor potential in breast cancer. However, the gene expression profile resulting from the action of DHA in breast cancer has not been elucidated yet. We aimed to examine the effects of DHA on normal breast cell line (HB4a), transformed cell line (HB4aC5.2) and breast cancer cell line (SKBR-3) and using a microarray approach. Cells were treated with 100?M of DHA for 72 hours. We identified 174, 208 and 126 differentially expressed genes after DHA treatment, in HB4a, HB4aC5.2 and SKBR3, respectively. Notably, the molecular pathways for the differentially expressed genes included those related to lipid metabolism, cell growth, molecular transport and cell-to-cell signaling. Where found genes related to overexpression of HER-2 after treatment with DHA. These genes involved in lipid metabolism and were down-expressed after treatment, suggesting a possible mechanism DHA in breast cancer by lipid metabolism control

Increasing level of public concerns about ageing and obesity problems accompanied by the advent of more and more health conscious consumers have put a priority on the health and wellness industry development which has started transformation from a niche category towards the mainstream. As a human being is an individual with unique known characteristics (like age, gender, health state, lifestyle) and less known characteristics like a genetic predisposition, the nutrition plan should be designed around these characteristics. Being aware of genetic predisposition of an individual allows to develop the appropriate health strategy for the particular individual. A systematization of these individual programs would support the development of a new generation of health practitioners. Russia is experiencing serious demographic problems with decreasing population and low life expectancy; high mortality rate from heart diseases and quite high obesity rates. It is expected that nutrigenomics concepts can be successfully developed in Russia due to its solid scientific base, relatively high level of medicine and the ever increasing awareness of the need for a healthy quality life especially within young generation. The goal of the thesis therefore is to analyze the key trends in the global and Russian food industries and develop a business idea of commercializing the personalized nutrition concept in the Russian food service market.

Le développement de la nutrigénétique/nutrigénomique (NGx) a suscité de nombreuses attentes puisque les retombées qui lui sont associées s’avèrent potentiellement bénéfiques autant pour les individus en santé que pour les individus malades. De grandes attentes avaient également été associées au Projet de décryptage du Génome Humain (PGH). Aujourd’hui, seules quelques attentes de celles envisagées se sont concrétisées. Le PGH a donc évolué dans un contexte marqué par du biohype, soit la promotion d’attentes exagérées, voir irréalistes. Étant donné l’importance des attentes associées avec le développement de la NGx et des limites méthodologiques auxquelles fait encore face la recherche clinique conduite dans ce domaine, l’objectif principal de cette thèse est de déterminer si les publications scientifiques rapportant des résultats de recherches cliniques effectuées en NGx contribuent à l’émergence d’un phénomène de biohype. Plus spécifiquement, il s’agira également de documenter la perception des chercheurs oeuvrant dans le domaine de la NGx du phénomène de biohype, d’identifier certains facteurs qui pourraient expliquer son émergence dans la littérature scientifique propre à ce domaine et de proposer des pistes d’actions pour limiter les risques associés à ce phénomène. Nous avons tout d’abord procédé à une analyse documentaire d’articles scientifiques rapportant des résultats issus de recherches cliniques en NGx. Celle-ci nous a révélé que plusieurs bénéfices étaient promus dans cette littérature alors même que les limites méthodologiques n’étaient pas d’emblée présentées et discutées. Cette observation nous portait à croire que ces bénéfices étant potentiellement prématurés. Nous avons ensuite voulu valider notre constat auprès des chercheurs œuvrant principalement dans le domaine de la NGx. Cette enquête nous a permis de constater que les chercheurs étaient généralement en accord avec les bénéfices que nous avons recensés dans les articles scientifiques. Toutefois, ils n’envisageaient pas leur concrétisation à moyen terme. Par ailleurs, cette enquête nous a également révélé que les limitations méthodologiques actuellement rencontrées dans la conduite de recherches cliniques soulevaient des doutes quant à la faisabilité des bénéfices promut dans les articles scientifiques. Ces données viennent confirmer notre observation à savoir qu’un phénomène de biohype serait réellement en émergence dans les articles scientifiques rapportant des résultats de recherches cliniques en NGx. Outre des informations concernant les publics ciblés par les chercheurs et les éléments que doivent contenir un article scientifique, cette enquête nous a également aidés à mieux comprendre les avantages associés à la promotion de bénéfices. Selon la majorité des chercheurs interrogés, la promotion de bénéfices dans un article scientifique augmenterait les chances d’un manuscrit d’être publié et favoriserait la continuité du financement du domaine de recherche. Cette activité étant caractérisée par un environnement compétitif, la promotion de bénéfices semble être une avenue à envisager pour se démarquer. Quoique la promotion de bénéfices prématurés ou exagérés ne soit pas considérée comme de l’inconduite scientifique, elle peut causer entre autres un affaiblissement du sentiment de confiance entre le public et les chercheurs et ultimement, contrevenir à la continuité d’une saine activité de recherche. À la lumière de ces données, nous croyons qu’une des stratégies qui permettrait de prévenir l’apparition des risques associés au phénomène de biohype serait de sensibiliser les chercheurs et les éditeurs de journaux scientifiques à ces derniers. Plus particulièrement, nous encourageons l’intégration de lignes directrices portant sur la gestion du biohype dans les codes de conduites qui ont été mis en place pour favoriser les bonnes pratiques en recherche. / The development of the nutrigenetics/nutrigenomics (NGx) has generated many expectations since the associated benefits are potentially beneficial for everyone, that is to say, both for healthy and sick individuals. High expectations were also associated with the Human Genome Project (HGP), but as of today only a few have been realized. The HGP thus evolved in a context marked by biohype, i.e., the promotion of exaggerated or unrealistic benefits. Given the importance of expectations associated with the development of NGx and the methodological limitations faced by clinical research conducted in this area, the main objective of this thesis is to determine whether scientific publications reporting results from clinical research conducted in Ngx contribute to the emergence of a biohype phenomenon. More specifically, it will also document the perception of researchers working in this area concerning this phenomenon, try to identify factors that could explain its emergence in scientific literature specific to NGx and suggest ways of actions to mitigate the risks associated with this phenomenon. We first conducted a document analysis of scientific articles reporting results from clinical research in NGx. This revealed that many benefits were promoted in the literature even though the methodological limitations were not necessarily presented or discussed. This observation led us to believe that the promoted benefits were potentially premature. We then sought to validate our findings among researchers working mainly in the field of NGx. Our survey revealed that researchers were generally in agreement with the benefits that we identified in the scientific articles. However, they did not consider that their realization was feasible in the medium term. This survey also revealed that the methodological limitations currently encountered in the conduct of clinical research raised doubts about the realistic outcome of the benefits promoted in scientific articles. These data confirm our observation that a biohype phenomenon is actually emerging in scientific articles reporting results of clinical research in NGx. Besides information about the audiences targeted by researchers and the elements that need to be included in a scientific article, the survey also helped us better understand the advantages associated with the promotion of benefits. The majority of researchers interviewed found that the promotion of benefits in a scientific article would increase the chances of a manuscript being accepted for publication and also foster continuing funding of the research area. In a competitive environment such as biomedical research, the promotion of benefits seems to be an avenue taken to stand out from the field. Although promoting premature or exaggerated benefits are not considered as being scientific misconduct, biohype can cause a weakening of the trust between the public and researchers. Ultimately, it can hinder the continuity of sound scientific research. Based on these findings, one of the strategies that could be use to prevent or mitigate the occurrence of the risks associated with biohype would be to increase awareness of the issue amongst researchers and scientific journal editors. Specifically, we encourage the integration of guidelines on the management of biohype within the codes of conduct that have been put in place to promote good practices in research.

Una dieta scorretta incrementa il rischio di malattie come l’insulino resistenza e l’obesità. Questa tesi ha l’obiettivo di valutare l’effetto di diete sbilanciate sulla fisiologia ed espressione genica in topi e suini allo svezzamento. Topi C57BL/6 sono stati sacrificati dopo 2 settimane, dopo essere stati alimentati con dieta iper-lipidica e dieta controllo. L’espressione genica è stata stimata usando la tecnologia microarray. Quattro dei sette geni identificati differenzialmente espressi tra il controllo e l’iper-lipidico sono coinvolti nella regolazione della via metabolica del sistema circadiano, che recentemente è stato mostrato avere effetti sul metabolismo lipidico e processo infiammatorio. Il secondo studio ha avuto lo scopo di capire gli effetti dello svezzamento con o senza l’aggiunta di acidificante nella dieta. I suinetti allo svezzamento (T0) sono stati comparati con i suinetti dopo una settimana (T1). Il gruppo post-svezzamento è stato alimentato con una dieta convenzionale, e metà di questi hanno ricevuto un supplemento di acido sorbico. L’aggiunta di acido sorbico nella dieta non ha causato nessuna differenza a livello fisiologico e di espressione genica. 205 geni sono stati identificati come differenzialmente espressi in T1 comparato con T0, evidenziando una forte risposta all’adattamento metabolico e agli stress subiti durante lo svezzamento. / An incorrect diet increases the risk of diseases as insulin resistance and obesity. This thesis aims at assessing the effects of unbalanced diets on gut physiology and gene expression in pig and mouse during weaning. The first research explored the impact of a high fat diet in C57BL/6 mice. High-fat-fed mice and control-fed mice were sacrificed after two weeks of treatment. Gene expression level was assessed by 90K Combimatrix microarray technology. Four of seven genes found differentially expressed between control and high fat diet mice are involved in the regulatory pathway of the circadian clock system, which was recently shown to affect lipid metabolism and inflammatory processes. Those genes were successfully validated by real time PCR. The second study aimed at understanding the weaning effect with or without acidifier addition in the diet. Piglets at weaning (T0) were compared to piglets after one week (T1). The post-weaning group was fed a conventional diet, half of which received in addition sorbic acid. The sorbic acid supplementation evidenced no effects in terms of physiology and gene expression. 205 genes were significantly differentially expressed in T1 when compared with T0, evidencing a response to the metabolic adaptation and the stress suffered during weaning.