The link between obesity and the risk of prostate cancer (PCa) is inconclusive. However, studies demonstrate a correlation between obesity, advanced PCa and mortality. Investigating the underlying biological mechanisms by which obesity promotes advanced PCa is necessary to develop potential therapeutic targets that may aid in the efficacy of treating obese men. Obesity-associated changes in tumor biology may modulate key aspects of the hallmarks of cancer; acquisition of characteristics essential for the development and progression of cancer. We hypothesized obesity-induced inflammation promotes PCa progression. Our studies incorporated cell culture and murine models to investigate the role of obesity-related systemic factors on AR signaling, inflammation-stimulated invasive PCa, and the paracrine interaction of the tumor-microenvironment (TME). We sought to recapitulate the systemic effects of obesity to investigate characteristics of the metastatic cascade. Briefly, sera from mice fed 60% or 10% kcal from fat diet for 12 weeks were used for in vitro studies. PCa cells exposed to sera from obese mice increased AR transcriptional activity, proliferation, invasion, migration, MMP-9 activity and EMT: e-cadherin, vimentin and β-catenin. PCa cells exposed to sera from 1 hour maintained the invasive phenotypes similar to PCa cells directly exposed to sera from obese mice. IL-6 is associated with advanced PCa cancer. Depleting sera of IL-6 or IL-6 shRNA suppressed obesity-induced proliferation, invasion, migration and MMP-9 activity in LNCaP cells. Furthermore, in a PTEN spontaneous model of PCa, IL-6 protein and mRNA levels corresponded with progression of PCa in mice fed a high-fat diet. These results suggest IL-6 mediates obesity-induced PCa progression. Stromal cells that comprise the TME vary in their contribution to the growth of tumors. Our studies show macrophage-like and myofibroblasts increased NF-kB activity in PCa cells exposed to sera from obese mice. An increase in NF-kB activity corresponded with proliferation, prostaglandin E2, and invasion and recruitment of stromal cells by PCa cells. In summary, obesity-related systemic factors promote an invasive PCa phenotype, which may be mediated by Akt, AR, IL-6 and the TME. Obesity-induced changes in tumor biology and the microenvironment provide a niche suitable for invasive prostate cancer. / text

The proposed study seeks to add to the literature surrounding the assessment of obesity-specific health related quality of life (HRQOL) among youth. Assessing this construct provides valuable information regarding the impacts of obesity on quality of life in childhood and adolescence. However, discrepant reports between caregivers and children can lead to difficulty in interpreting assessment data. Using multiple regression, this study will explore whether observed differences in caregiver and child reports of obesity-specific HRQOL can be predicted by caregiver and child variables in a treatment-seeking sample. Variables of interest include parenting stress, body mass index (BMI), age, and gender. Significant results may help clinicians develop hypotheses about the causes of discrepancies when conceptualizing cases. / text

published_or_final_version / Pharmacology and Pharmacy / Doctoral / Doctor of Philosophy

Objective: To systematically review the feasibility and effectiveness of recent school lunch interventions in primary schools and whether they instil positive changes to childhood dietary habits and help prevent obesity. Background: Childhood obesity is a growing concern affecting 42 million children (2010) and increasing daily, and may be linked to adult obesity. Lunch contributes 24% of daily energy, making school lunch interventions monumentally important in reducing consumption of high fat and/or sugar foods, and increasing fruit and vegetable (F&V) intake. Methods: A literature search was conducted for studies with interventions in primary school environments that aimed to alter the consumption of fruits, vegetables, and unhealthy foods high in fat or sugar. Studies were only suitable if they utilized randomized controlled trial (RCT) or cluster RCT designs, and included relevant outcome measures for F&V or macronutrient consumption. Relevant studies published between January 1st 2000 and May 31st 2013 were identified through PubMed, ISI Web of Science, and Cochrane Trials, and bibliographies of relevant studies. Results: Nine studies were included in this systematic review from the US or UK, with varied direct and indirect interventions to alter school lunch nutrition either through F&V or improved macronutrient content. Environmental changes to child attitudes towards F&V, such as verbal encouragement, classroom curriculums and audio-visual stimuli, were significantly effective in all 4 studies, whereas 2 studies with changes to F&V availability without involving students had mixed results. Direct reductions to fat content in school lunches produced significant results in 2 of 4 studies, with increased carbohydrate intake compensating for lower fat, resulting in non-significant total energy changes. One of 3 environmental interventions also had similar trends in macronutrient intake. Total energy change was only significant in 1 of 6 studies. Conclusion: Overall interventions for childhood obesity had moderate success, and most were unable to meet primary dietary goals set out by researchers. Ineffectiveness of interventions may be due to parental influences at home, early childhood dietary habits, disproportionately low SES in study samples, among other factors. Further research on targeting calorie intakes, parental involvement, snack food reduction, and related fields is recommended. / published_or_final_version / Community Medicine / Master / Master of Public Health

The primary goal was to study the influence of adipocyte number and volume, inflammation, insulin resistance, and genetic factors on indicators of liver injury, surrogate marker of non alcoholic fatty liver disease (NAFLD). The secondary goal was to explore the occurrence of NAFLD and its relationship with variations in liver function biomarkers. The first objective was to determine the association of plasma levels of monocyte chemoattractant protein-1 (MCP-1) with omental adipocyte number, insulin resistance and circulating concentrations of liver injury markers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in unrelated baboons. Significant associations of MCP-1 with other measured traits were established. The second objective was to examine if adiposity-related parameters are under genetic influence and to evaluate their genetic correlations with AST in pedigreed baboons. Adipocyte volume and number, body weight and plasma AST were heritable. Genetic correlations between adiposity-related phenotypes and AST were significant. A genome wide scan yielded a strong signal for adipocyte volume on chromosome 6. The third aim was to explore the genetic factors that influence variations in plasma levels of [gamma] glutamyl transferase (GGT) and albumin (ALB), and to evaluate their genetic correlations with cardiovascular risk factors in pedigreed baboons. Significant linkages for GGT and albumin were identified on chromosome 20_22 and chromosome 10, respectively. Genetic correlations between ALB and cardiovascular risk factors were significant. No statistically significant associations were found between GGT and cardiovascular-related phenotypes. The fourth objective was to investigate the prevalence of NAFLD and its association with altered liver protein levels in unrelated baboons. The influence of weight and insulin resistance on the occurrence of NAFLD was inconclusive. Significant relationships between the variations in plasma levels of liver injury biomarkers and severity of the disease could not be established. In conclusion, the first three studies provided observational and genetic evidence of a relationship between liver function markers and adiposity-related factors in baboons. However, the results of the fourth study do not provide conclusive evidence to suggest that body weight and insulin resistance play a significant role in the development of NAFLD in these baboons.

Obesity is a pervasive condition associated with increased risk of dementia, cognitive impairment, and cerebral atrophy in later life. Given that the pathophysiology underlying obesity’s impact on the central nervous system is poorly understood, the current study examined the association between body mass index (BMI) and five cerebral metabolites of neurobiological significance: N-acetyl-aspartate (NAA), a marker of neuronal viability; choline-containing compounds, free choline, phosphocholine and glycerophosphocholine (Cho), markers of membrane breakdown and turn over; creatine (Cr), a marker of energy metabolism; myo-inositol (mI), an organic osmolyte and substrate for the synthesis of the secondary messenger, inositol triphosphate; and glutamate (Glu), a marker of excitatory neurotransmission and synaptic integrity. Fifty-five participants, aged 40-60 years, underwent neuropsychological testing, health screen and proton magnetic resonance spectroscopy (1H MRS) of the occipitoparietal grey matter. Concentrations of NAA, Cho, mI, and Glu were calculated as a ratio over Cr and examined in relation to BMI using multivariate multiple regression. Higher BMI was associated with elevations in mI/Cr (F(5,47)=3.583, p=0.008, ß=0.387, p=0.006), independent of age, sex, fasting glucose levels, and systolic blood pressure. The current study found that higher BMI is related to increased concentrations of the organic osmoltye and glial marker myo-inositol, potentially implicating plasma hypertonicity and neuroinflammation as mechanisms underlying obesity-related brain dysfunction. With validation and absolute quantification, studies of neurometabolites may improve identification of the pathological mechanisms underlying obesity’s consequences on cognition. / text

Emerging adulthood is a time of significant change where behaviors are adopted that can have significant long term effects on health. The most dramatic increases in weight are occurring among emerging adults, especially those with some college education. Emerging adults are also at an increased risk for substance use and abuse. The current study examined the relationship between BMI and substance use among college students. Participants included 703 undergraduate students at a large public U.S. university (M age=20.6, 58.7% Non-Hispanic White, 59.8% female). Students completed an online survey with items on substance use behaviors such as smoking, alcohol use, marijuana use, and binge drinking. Tobacco, alcohol, marijuana use, and binge drinking were assessed with one question asking students how many days over the past month they had used the specific substance (range 0-30 days). Binge drinking was assessed using one question: “Over the last two weeks, how many times have you had five or more drinks of alcohol at a sitting?” Responses ranged from 0 to 10 or more times. Substance use behaviors were coded to no use/any use in the past month. Body mass index was calculated through the student’s self reported height and weight. BMI was significantly related to past month tobacco use with an odds ratio of 1.06 (95% CI: 1.01-1.12). Specifically, with every one unit increase in BMI, the odds of past month tobacco use increased by 6%. However, BMI was not significantly associated with past month alcohol use, marijuana use, or binge drinking (p>.05). As BMI increases, college students’ odds of using tobacco increase. This finding is particularly problematic given that weight gain is common among undergraduate students and cigarette use has been cited as a common weight management practice among this group as well. Future research should consider the role of BMI as a factor in decreasing tobacco use. / text

No description available.

Η παιδική παχυσαρκία είναι ένας από τους κύριους παράγοντες κινδύνου για ανάπτυξη: Σακχαρώδη Διαβήτη Τύπου ΙΙ, δυσλιπιδαιμίας και καρδιοαγγειακών παθήσεων. O λιπώδης ιστός θεωρείται ως ένα όργανο ενδοκρινές και παρακρινές, το οποίο εκκρίνει ποικίλες κυτταροκίνες και άλλους σημαντικούς μεταβολικούς παράγοντες. Η λιπογένεση και η λιπόλυση διενεργούνται στα λιποκύτταρα με σκοπό να διατηρηθεί η ενεργειακή ισορροπία. Τα λιποκύτταρα αποθηκεύουν τριγλυκερίδια όταν η ενεργειακή πρόσληψη είναι σε υψηλά επίπεδα, ενώ σε αντίθετη περίπτωση, τα λιποκύτταρα απελευθερώνουν στο αίμα ελεύθερα λιπαρά οξέα και γλυκερόλη, διαδικασία που επιτυγχάνεται μέσω της υδρόλυσης των τριγλυκεριδίων. Η ακουαπορίνη-7 [aquaporin-7 (AQP7)] είναι μια ακουα-γλυκεροπορίνη, η οποία ρυθμίζει τη μεταφορά της γλυκερόλης μέσα κι έξω από το λιποκύτταρο, όπως επίσης και τη διακίνηση του νερού. Η AQP7 εντοπίζεται περιπυρηνικά. Όταν γίνεται λιπόλυση, η επινεφρίνη αυξάνεται και παράλληλα αυξάνει τα επίπεδα του AMP, διαμέσου της ενεργοποίησης των αδρενεργικών υποδοχέων οι οποίοι διαδοχικά ενεργοποιούν την πρωτεϊνική κινάση Α. Η πρωτεϊνική κινάση Α με τη σειρά της φωσφορυλιώνει την περιλιπίνη, η οποία καθιστά ικανή τη φωσφορυλιωμένη ορμονο-ευαίσθητη λιπάση να υδρολύσει τα τριγλυκερίδια σε λιπαρά οξέα και γλυκερόλη, προκαλώντας τη μετακίνηση της AQP7 στην πλασματική μεμβράνη ώστε να επιτευχθεί η απελευθέρωση της γλυκερόλης. Σκοπός: 1) Η ανίχνευση πολυμορφισμών και μεταλλάξεων στον υποκινητή του γονιδίου της AQP7 σε προεφηβικά και εφηβικά παιδιά με νοσογόνο παχυσαρκία σε σύγκριση με αντίστοιχα λεπτόσωμα παιδιά. 2) Η συσχέτιση των επιπέδων στον ορό του αίματος των παιδιών αυτών της γλυκόζης νηστείας, τριγλυκεριδίων, χοληστερίνης, HDL και LDL και των δεικτών γενικευμένης παχυσαρκίας (ΒΜΙ %) και κεντρικής παχυσαρκίας (περίμετρο μέσης) με τυχόν πολυμορφισμούς ή μεταλλάξεις στον υποκινητή της AQP7. Μέθοδοι και Υλικά: Συλλέχθησαν αίματα από 64 λεπτόσωμα και 38 παχύσαρκα προεφηβικά και εφηβικά παιδιά. Συλλέχθηκαν τα στοιχεία του ιστορικού και της φυσικής εξέτασης (ΒΜΙ %, περίμετρο μέσης, Tanner στάδιο εφηβείας,) και των επιπέδων γλυκόζης, τριγλυκεριδίων, χοληστερίνης, HDL και LDL. Πραγματοποιήθηκε απομόνωση DNA (NucleoSpin® Blood Quick Pure- Macherey Nagel kit). Έγινε PCR για τον υποκινητή του γονιδίου της AQP7 (4 σετ εκκινητών: PR1a, PR1b, PR2a και PR2b). Έγινε ηλεκτροφόρηση των προϊόντων της PCR και gel extraction (Sigma Aldrich, Sigma-GenΕlute Gel Extraction kit). Τέλος, τα δείγματα στάλθηκαν για αλληλούχιση στη Λάρισα, στη Σχολή επιστημών Υγείας, στο Τμήμα Ανοσολογίας της Ιατρικής του Πανεπιστημίου Θεσσαλίας. Αποτελέσματα: Μετά την αλληλούχιση των δειγμάτων, πραγματοποιήθηκε σύγκριση της αλληλουχίας του κάθε δείγματος, με την αλληλουχία του υποκινητή όπως έχει ταυτοποιηθεί από τους Kondo H. et al. (2002) και βρέθηκαν οι εξής μονονουκλεοτιδικοί πολυμορφισμοί [single nucleotide polymorphisms (SNPs)] στον υποκινητή του γονιδίου της AQP7: στη θέση -2291(A2710G) του υποκινητή του γονιδίου της AQP7, όπου βρέθηκε αλλαγή βάσης από αδενίνη σε γουανίνη, στη θέση -2219(C2782A), όπου βρέθηκε αλλαγή βάσης από κυτοσίνη σε αδενίνη, στη θέση -2091(C2910Α), όπου βρέθηκε αλλαγή βάσης από κυτοσίνη σε αδενίνη, στη θέση -1884(C3117T), όπου βρέθηκε αλλαγή βάσης από κυτοσίνη σε θυμίνη, στη θέση -1123(C3878T), όπου βρέθηκε αλλαγή βάσης από κυτοσίνη σε θυμίνη και στη θέση -953(Α4048G), όπου βρέθηκε αλλαγή βάσης από αδενίνη σε γουανίνη. Πραγματοποιήθηκε συσχέτιση των ατόμων που έχουν τους μονονουκλεοτιδικούς πολυμορφισμούς στις παραπάνω θέσεις με τα κλινικά τους χαρακτηριστικά και βρέθηκε στατιστικώς σημαντικά ότι στα άτομα που έχουν τους πολυμορφισμούς στις θέσεις -2219(C2782A),-2091(C2910Α) και -1884(C3117T) η HDL χοληστερόλη μειώνεται (p<0.05). Επίσης, βρέθηκε ότι υπάρχει στατιστικώς σημαντική αύξηση του ΒΜΙ επί τοις εκατό, στα άτομα που έχουν τον πολυμορφισμό -1123(C3878T), (p=0,035). Τέλος, βρέθηκε ότι υπάρχει στατιστικώς σημαντική αύξηση στην περίμετρο μέσης επί τοις εκατό, στα άτομα που έχουν τον πολυμορφισμό -953(Α4048G), (p=0,033) και ότι τα άτομα αυτά έχουν συσχέτιση με την ύπαρξη οικογενειακού ιστορικού για Σακχαρώδη Διαβήτη Τύπου ΙΙ (p=0,033). Συμπεράσματα: 1) Ο συνδυασμός δύο ή και περισσότερων πολυμορφισμών στις παρακάτω περιοχές του υποκινητή της AQP7: -2219(C2782A), -2091(C2910Α) και -1884(C3117T), έχει βρεθεί σε 7 μάρτυρες. Τέσσερις από τους μάρτυρες αυτούς έχουν οικογενειακό ιστορικό για Σακχαρώδη Διαβήτη Τύπου ΙΙ και 3 έχουν περίμετρο μέσης μεγαλύτερη του 75%. Επίσης, βρέθηκε ότι τα άτομα που έχουν τους πολυμορφισμούς αυτούς, έχουν μειωμένη HDL χοληστερόλη. Τα ευρήματα αυτά πιθανώς καταδεικνύουν τη μεταγενέστερη εξέλιξη των παιδιών αυτών σε παχύσαρκους ενήλικες, μιας και εμφανίζουν αρκετά στοιχεία του Μεταβολικού Συνδρόμου. 2) Οι πολυμορφισμοί του υποκινητή του γονιδίου της AQP7 -1123(C3878T) και -953(Α4048G), βρέθηκαν κυρίως σε παχύσαρκα παιδιά. Οι πολυμορφισμοί αυτοί βρίσκονται σε περιοχές όπου προσδένεται ο μεταγραφικός παράγοντας C/EBPβ και από μελέτες έχει βρεθεί ότι ο -953(Α4048G) μειώνει την έκφραση της AQP7 και σχετίζεται με την εμφάνιση Σακχαρώδη Διαβήτη Τύπου ΙΙ. Τα παιδιά που είχαν τον πολυμορφισμό -1123(C3878T) είχαν αυξημένο BMI% και τα παιδιά που είχαν τον πολυμορφισμό -953(Α4048G) είχαν συσχέτιση με την ύπαρξη οικογενειακού ιστορικού για Σακχαρώδη Διαβήτη Τύπου ΙΙ και αυξημένη περίμετρο μέσης επί τοις εκατό. Τα ευρύματα αυτά σε συνάρτηση με τα ευρύματα προηγούμενων μελετών στους ενήλικες καταδεικνύουν τη μειωμένη έκφραση της AQP7 στα παιδιά αυτά, τον κίνδυνο για την μελλοντική ανάπτυξη σοβαρής Παχυσαρκίας και Σακχαρώδη Διαβήτη Τύπου ΙΙ. / Childhood obesity is one of the main risk factors for the development of Diabetes Mellitus II, dyslipidemia and cardiovascular diseases. Adipose tissue is considered as an endocrine and paracrine organ that secretes a variety of cytokines and other important metabolic factors. Ljpogenesis and ljpolysis are held in adipocytes with a view to maintain the energy balance. Adipocytes store triglycerides when the energy uptake is in high levels, while in opposite case, adipocytes release free fatty acids and glycerol in the blood, a process that is achieved via the hydrolysis of triglycerides. Aquaporin -7 (AQP 7) is an aqua-glyceroporin, which regulates the transport of glycerol inside and outside from adipocytes, as also the distribution of water. AQP 7 is located perinuclear. During ljpolysis, the epinephrine is increased and this event increases the levels of AMP, through the activation of adrenergic agonists that successively activate protein kinase A. Protein kinase A phosporylates perilipin, which renders capable the phosporylated hormone-sensitive lipase to hydrolize triglycerides in fatty acids and glycerol, causing the translocation of AQP 7 in the plasma membrane so that is achieved the release of glycerol. Aim: 1) The detection of polymorphisms and mutations in the promoter of gene of AQP 7 in prepubertal and adolescent children with pathogenic obesity compared to respectively lean children. 2) The cross-correlation of levels in the serum of blood of this children of glucose of fast, triglycerides, cholesterol, HDL and LDL and indicators of generalised obesity (BMI %) and central obesity (waist circumference) with any chance of polymorphisms or mutations in the promoter of AQP 7. Methods and Materials: Collected blood from 64 lean and 38 obese prepubertal and adolescent children. Collected the data of history and natural examination (BMI %, waist circumference, Tanner stage of puberty) and levels of glucose, triglycerides, cholesterol, HDL and LDL. DNA extraction by the NucleoSpin ® Blood Quick Pure - Macherey Nagel kit. PCR for the promoter of gene of AQP7 with 4 set of primers: PR 1 a, PR 1 b, PR 2 a and PR 2 b. Elecrophoresis of PCR products and gel extraction (sigma Aldrich, -genElute Gel Extraction kit). Finally, the samples were sent for sequencing in Larissa, in the Faculty of sciences of Health, in the Department of Immunology of Medicine of Thessaly University. Results: Afterwards the sequencing of samples, the sequence of each sample, was compared with the sequence of the promoter as it identified from Kondo H. et al. (2002). The following single nucleotide polymorphisms (SNPs) were found in the promoter of gene of AQP7: in the site -2291(A2710 G) of the promoter of gene of AQP 7, was found change of base from adenine to guanine, in the site -2219 (C 2782 A), was found change of base from cytosine to adenin, in the site -2091 (C 2910A), was found change of base from cytosine to adenin, in the site -1884 (C 3117 T), was found change of base from cytosine to thymine, in the site -1123(C 3878 T), was found change of base from cytosine to thymine and in the site -953(A4048 G), was found change of base from adenine to guanine. After cross-correlation of individuals that has the above SNPs with clinical characteristically, was found statistically significant decreased HDL cholesterol in the individuals that have the polymorphisms in the sites -2219(C 2782 A), -2091 (C 2910A) and -1884 (C 3117 T ), (p < 0.05). Also, was found statistically significant increase of BMI%, in the individuals that have the polymorphism -1123(C 3878 T), (p = 0,0 35). Finally, was found statistically significant increase in the waist circumference% (WC%), in the individuals that have the polymorphism -953(A4048 G), (p = 0,0 33) and that these individuals have cross-correlation with the existence of familial history for Diabetes Mellitus II (p = 0,033). Conclusions: 1) The combination of two or even more polymorphisms in the following regions of promoter of AQP 7: - 2219 (C 2782 A), -2091(C 2910A) and -1884(C 3117 T), has been found in 7 lean children. Four of these children have familial history for Diabetes Mellitus II and 3 have WC% > 75%. Also, was found that the individuals that have these polymorphisms, have decreased HDL cholesterol. These findings show the later development of these children in obese adults, as they present enough elements of Metabolic Syndrome. 2) The polymorphisms of promoter of gene of AQP7 -1123(C 3878 T) and -953(A4048 G), were found mainly in obese children. These polymorphisms are found in regions where was bind the transcription factor C / EBP b and studies has been found that the -953(A4048 G) decreases the expression of AQP 7 and is related with the appearance of Diabetes Mellitus II. Children that had the polymorphism -1123(C 3878 T) had increased BMI % and children that had the polymorphism -953(A4048 G) had cross-correlation with the existence of familial history of Diabetes Mellitus II and increased WC%. These findings in combination with findings of previous studies in adults show the decreased expression of AQP7 in these children, the danger for the future development of serious Obesity and Diabetes Mellitus II.

No description available.