The prevention of childhood obesity during the formative years is necessary because dietary patterns influenced by parents are developed early. A major obstacle to healthy feeding patterns in children is television advertising. The study tested three hypotheses. 1) Preschool children ages two to five years who watch more television are able to recognize/recall more food brands than those who view less television. 2) An increase in food brand recognition/recall in preschool children is associated with an overweight classification based on calculated Body Mass Index. 3) Children of parents who are unaware of the American Academy of Pediatrics (AAP) recommendations for television viewing per day in preschool children will exceed the recommended daily viewing time of two hours. Twenty-nine preschool children were assessed on their ability to match food brand logos with correct foods and identify specific brands from recall. Weight and\ height were measured to calculate their Body Mass Index-for age. Twenty-eight parents were asked to complete a validated survey and a one-week television diary. The results showed statistically significant differences in identifying food brands between children who had lower exposure to television (6.8±.5; 95% CI 5.95-7.55) compared to higher exposure (10.3±1.0; 95% CI 9.25-11.42). This effect was not significantly correlated with overweight status (n=5). No significant correlations were found between parent's knowledge of AAP recommendations and children's exposure to television. Impact of television advertisements on preschool children's response to food/brand logos due to daily exposure to advertising is still of critical interest and worthy of further exploration.

Fruit and vegetable derived polyphenols have been linked with many health benefits. In light of this, many consumers are seeking to increase their intake of polyphenols, with many turning to dietary supplements that contain concentrated doses of purified polyphenols. However, the safety of this consumption modality is not known, nor are the dose-dependent metabolic changes that may be present, especially when considering colonically generated phenolic metabolites. Using blueberry polyphenols as a model, we explored these phenomena in a rat model. Animals were dosed with blueberry polyphenols at levels up to 20 times what would be consumed in 1-2 servings of whole blueberries in an adult human. In the first study, animals were acutely dosed with blueberry polyphenols and urine and plasma pharmacokinetics measured. In the second study, animals were repeatedly dosed for 90d, with urinary metabolites monitored throughout the study and a complete necropsy performed following standard guidelines. In both studies, metabolite excretion patterns were similar: cinnamic acids accounted for a majority of the observed metabolites, followed by hippuric acids and then phenylpropionic acids (PPA). A dose-dependent shift in metabolite production was observed; as the dose increased, the relative amounts of PPA increased while hippuric acids decreased. No adverse or toxic effects were found, and, though there were several statistically significant differences in toxicological endpoints, all measured parameters remained in the normal range for these animals and thus were not deemed biologically significant. These results indicate that high doses of blueberry polyphenols, as may be present in dietary supplements, are safe for consumption. These results also demonstrate dose-dependent shifts in metabolism that may impact gut function and affect the health benefits derived from blueberry polyphenols.<br>

<p>As obesity has become one of the most prevalent metabolic diseases, and diabetes mellitus has become the seventh leading causes of death in the United States, alternative food/nutrition-based approaches to tackle obesity that are both efficacious and cost effective are in high demand. Since starch and its derived products are the principal dietary supply of glucose, strategies of using slowly digestible starch to achieve moderated glycemic response and prolonged glucose delivery, as well as to locationally digest starch into the ileum, have shown successful results such as moderation of insulinemia and reducing food intake in obese animals. An important regulator of appetite suppression is the neuroendocrine system of the gut-brain axis. Glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY) are the main anorexigenic peptide products of the intestinal enterendocrine L-cells that regulate postprandial insulin levels as well as satiety signals. The stimulation of the enteroendocrine L-cells throughout the gastrointestinal tract through glucose, fatty acids and proteins has been extensively studied and confirmed. However, the stimulatory effect of complex dietary carbohydrates on L-cells is not described. In this dissertation, we investigated the <i>in vitro</i> intestinal cell chemosensation of L-cells to α-amylase starch digestion products, named maltooligosaccharides (MOS), and in the possible application of using slowly digestible starch delivery of MOS <i>in vivo</i>.</p> <p>In Chapter II of this dissertation, we reported a significantly higher stimulatory effect of MOS on GLP-1 and OXM secretion compared to glucose in mouse and human L-cells, respectively. Additionally, maltotriose enhanced the relative expression of the gastrointestinal peptide, cholecystokinin. Moreover, MOS exhibited protective effects on barrier function and monolayer integrity of intestinal epithelial cells. </p> <p>In Chapters III and IV, we performed a multiomics approach where transcriptomic analysis and global protein profiling of mouse L-cells treated with different types of MOS showed that the carbohydrates exhibit their effects through the induction of exocytosis of GLP-1- or OXM-containing vesicles and not through a positive regulation of the proglucagon gene expression. It is suggested that MOS induce higher secretion, but not higher synthesis, of the proglucagon gene products. In addition, maltotriose treatment downregulated the relative expression of the glucotoxicity marker, thioredoxin-interacting protein, and upregulated the relative expression of tight junction proteins supporting a role of MOS in barrier function integrity.</p> <p>Translating the <i>in vitro</i> findings into an <i>in vivo</i> application that is beneficial for human health required the use of controllable tool for the delivery of MOS throughout the small intestine for sensing by a higher number of L-cells. Slowly digestible starch (SDS), compared to rapidly digestible starch, provided such a tool. For this purpose, we used alginate-entrapped SDS microspheres that digest distally into the ileum to examine the role of SDS in the intervention and prevention of obesity in C57BL/6J diet-induced obese (DIO) and lean mice models.</p> <p>Results showed that 20% SDS in low-fat diets significantly improved weight loss and food intake reduction in DIO mice converted to low-fat diet for 12 weeks. Similarly, 15% SDS in high-fat diets showed significant reduction in body fat percent and significant increase in lean body mass as well as considerable reduction in weight gain rate and food intake in lean mice fed on 45% of calories high-fat diet. Immunohistochemistry of small intestine of mice in both the intervention and prevention studies revealed an even and thorough distribution of GLP-1 positive L-cells.</p> <p>Overall, this dissertation proposes several insights into L-cell sensation of dietary starch-degraded MOS delivered by the consumption of slowly digestible starch. MOS exhibit unique influences on L-cell sensitivity and gut hormone productivity. Future research investigating the mechanisms of intestinal sensing of MOS, as well as the development of bioactive carbohydrate structures that could preserve body weight and modulate glucose tolerance <i>in vivo</i> is needed to translate these findings into nutritional recommendations and food products beneficial for human health. The intricate role of dietary carbohydrates on gut physiological response, related to satiety and food intake could be a new approach for design of foods for health applications.</p>

The project was carried out in collaboration with Lantmännen with the aim to analyse the lipase activity in oat endosperm, non-heat-treated whole grain oat flour and heat-treated whole grain oat flour and to investigate whether lipase activity could be inactivated in oat endosperm by reducing water activity by various methods such as oven drying and freeze drying to extend oat shelf life. Lipase activity was measured by a wet extraction of the flour and an artificial substrate that gives a coloured product if lipase enzymes are active in the extract. The formation of the product was measured during five minutes at room temperature or 37 °C using a spectrophotometer, and the enzyme activity in units/g of flour was calculated. It was not possible to measure the enzyme activity in the flour directly. The obtained results for the different oat fractions indicated differences in lipase activity between the oat fractions. Lipase activity for oat endosperm was 0.183 U/g, lipase activity for non-heat-treated whole grain oat flour was 0.088 U/mg and the heat-treated whole grain oat flour had no lipase activity. The differences were statistically significant since the p-value was &lt;0.0001. The results from the analysis that compared whether oven-drying and freeze-drying as methods had an effect on lipase activity indicated that oven drying had the greatest effect when assay was performed at room temperature. However, when the assay was performed at 37 °C the lipase activity in oven-dried and freeze-dried oat endosperm were similar to non- treated samples. This indicates that temperature has a great impact on the lipase activity. Thus, oven drying and freeze drying could not completely inactivate the lipase activity, but probably reduce it.

<p>Colorectal cancer is one of the leading causes of cancer deaths in the United States and multiple modifiable factors contribute to colorectal carcinogenesis. Gut microbiota are believed to play key roles in colon cancer development. Dietary factors may modulate gut microbiota composition, which may potentially have impact on carcinogenesis. Thus, it is reasonable to develop dietary interventions to effectively prevent colorectal cancer development through alteration of gut microbiota. In this thesis, the first objective is to evaluate the effect of vitamin E forms and metabolites, i.e., δ-tocotrienol (δTE), γ-tocotrienol (γTE) and δTE-13’-COOH (δTE-13’), respectively, on gut microbiota in mice. Healthy male balb/c mice were supplemented with a δTE/γTE mixture or δTE-13’ by gavage for two weeks, while control mice received soybean oil. We isolated DNAs from fecal samples and used 16S rRNA gene sequencing to evaluate the impact of these compounds on gut microbiota compositions. Further, we also examined the effect on short chain fatty acids (SCFAs). We observed that supplementation of δTE-13’ increased microbial richness using the Faith index. On the other hand, supplementation did not separate the microbial communities from the control group. But, these compounds managed to alter the relative abundances of several taxa that might present chemopreventive activities against colon cancer. Specifically, <i>Desulfovibrio</i>, a sulfur-reducing bacterium, was decreased after δTE/γTE supplementation. <i>Eubacterium coprostanoligenes</i> group, a group of microbes that can reduce circulating cholesterol, was increased after δTE/γTE supplementation. In addition, several members from the <i>Lachnospiraceae</i> family were elevated under δTE/γTE and δTE-13’ supplementation, and these microbes are known to produce SCFAs and maintain colonic health. However, the measurement of SCFAs showed that supplementation of δTE/γTE and δTE-13’ did not change SCFAs compared with controls. In the second project, I investigated anti-proliferative effects of combining δTE or δTE-13’ with sodium butyrate (NaBu) on human colorectal carcinoma HCT116 cells. Our data showed promising additive effects against cell growth. Collectively, these results indicate that δTE/γTE and δTE-13’ can modulate gut microbiota under healthy conditions, which provides insights into potential chemopreventive activities of these vitamin E forms. Our cell-based studies also showed additive anticancer effects of combining δTE or δTE-13’ with NaBu, which provides rationale to further develop combination of butyrate producers with vitamin E forms for cancer prevention.</p>

<p>Breast cancer is the predominant cancer diagnosed among women, and the second most deadly cancer. The vast majority of cancer-related deaths is caused by the metastatic spread of cancer from the primary tumor to a distant site in the body. Therefore, new strategies which minimize breast cancer metastasis are imperative to improve patient survival. Cancer cells which acquire anchorage independence, or the ability to survive without extracellular matrix attachment, and metabolic flexibility have increased potential to metastasize. In the present studies, the ability to survive detachment and subsequent metabolic changes were determined in human Harvey-<i>ras</i> transformed MCF10A-<i>ras</i> breast cancer cells. Detachment resulted in reduced viability in a time-dependent manner with the lowest cell viability observed at forty hours. In addition, decreased cell viability was observed in both glutamine and glucose depleted detached conditions, suggesting a dependence on both nutrients for detached survival. Compared to attached cells, detached cells had reduced total pool sizes of pyruvate, lactate, α-ketoglutarate, fumarate, malate, alanine, serine, and glutamate, suggesting the metabolic stress which occurs under detached conditions. However, intracellular citrate and aspartate pools were unchanged, demonstrating a preference to maintain these pools in detached conditions. Compared to attached cells, detached cells had suppressed glutamine metabolism, as determined by decreased glutamine flux into the TCA cycle and reduced mRNA abundance of glutamine metabolizing enzymes. Further, detached glucose anaplerosis through pyruvate dehydrogenase activity was decreased, while pyruvate carboxylase (PC) expression and activity were increased. A switch in metabolism was observed away from glutamine anaplerosis to a preferential utilization of PC activity to replenish the TCA cycle, determined by reduced PC mRNA abundance in detached cells treated with a cell-permeable analog of α-ketoglutarate, the downstream metabolite of glutamine which enters the TCA cycle. These results suggest that detached cells elevate PC to increase flux of carbons into the TCA cycle when glutamine metabolism is reduced. </p> <p>Vitamin D is recognized for its role in preventing breast cancer progression, and recent studies suggest that regulation of energy metabolism may contribute to its anticancer effects. Vitamin D primarily acts on target tissue through its most active metabolite, 1α,25-dihydroxyvitamin D (1,25(OH)₂D). The present work investigated 1,25(OH)₂D’s effects on viability of detached cells through regulation of energy metabolism. Treatment of MCF10A-<i>ras</i> cells with 1,25(OH)₂D resulted in decreased viability of detached cells. While 1,25(OH)₂D treatment did not affect many of the glucose metabolism outcomes measured, including intracellular pyruvate and lactate pool sizes, glucose flux to pyruvate and lactate, and mRNA abundance of enzymes involved in glucose metabolism, 1,25(OH)₂D treatment reduced detached PC expression and glucose flux through PC. A reduction in glutamine metabolism was observed with 1,25(OH)₂D treatment, although no 1,25(OH)₂D target genes were identified. Further, PC depletion by shRNA decreased cell viability in detached conditions with no additional effect with 1,25(OH)₂D treatment. Moreover, PC overexpression resulted in increased detached cell viability and inhibited 1,25(OH)₂D’s negative effects on viability. These results suggest that 1,25(OH)₂D reduces detached cell viability through regulation of PC. Collectively this work identifies a key metabolic adaptation where detached cells increase PC expression and activity to compensate for reduced glutamine metabolism and that 1,25(OH)₂D may be utilized to reverse this effect and decrease detached cell viability. These results contribute to an increased understanding of metastatic processes and the regulation of these processes by vitamin D, which may be effective in preventing metastasis and improve breast cancer patient survival.</p>

Inledning: Den svenska träningstrenden fortsätter enligt stadiums årliga undersökning om svenskarnas träningsvanor. Enligt Livsmedelsverket är kosttillskott ett komplement som ska konsumeras utöver den vanliga kosten, och motiveringen till att idrottare använder kosttillskott är exempelvis för att skydda hälsa och prestation. Proteintillskott konsumeras för att öka proteinsyntesen och påverkar muskelfunktioner och träning positivt. Studier har tidigare undersökt atleters inställning till kosttillskott, men få studier har undersökt inställningen till proteintillskott hos människor som har styrketräning som ett fritidsintresse.       Syfte: Studien avser att undersöka inställningen till användandet av kosttillskott i form av protein (proteinpulver, bars). Studien ska också undersöka proteinintaget hos användare och icke-användare av proteintillskott.   Material och metod: Studien utgjordes av en webbaserad enkät och en kostregistrering. Inklusionskriterierna för att delta i studien var att träna minst tre gånger i veckan, vara man och minst 18 år gammal. Rekryteringen genomfördes via en Facebook grupp som riktar sig mot dom som har ett intresse för träning och hälsa.    Resultat: Totalt deltog tio personer i kostregistreringen. Det förekom underrapportering av energiintaget i samtliga kostregistreringar, vilket påverkar resultatets trovärdighet. Det fanns en viss skillnad i proteinintaget mellan användare och icke-användare av proteintillskott, och icke-användare av proteintillskott konsumerade mer animalieprodukter än användare. Det var 26 personer som besvarade enkäten, och var mellan 18–50 år gamla och tränade minst tre gånger i veckan på gym. Svarsfrekvensen på frågorna varierade eftersom det var öppna frågor. Anledningen för att använda proteintillskott är att få i sig extra protein, och anledningen för att inte använda proteintillskott är för att de får i sig tillräckligt med protein från den vardagliga kosten.   Slutsats: Trots osäkerheten i rapporterade data av energiintaget visar kostregistreringarna att användare av proteintillskott till stor del förlitar sig på att proteintillskott täcker proteinbehovet, och konsumtions skillnaden av olika typer av livsmedelsgrupper var framförallt animalieprodukter. Anledningen till att avstå från proteintillskott är huvudsakligen på grund av kostnaden och dess effekt. / Introduction: The Swedish training trend continues according to Stadiums annual survey of Swedes' training habits. Dietary supplements are a supplement that should be consumed in addition to the usual diet, and the motivation for athletes to use dietary supplements is, for example, to protect health and performance. Protein supplements are consumed to increase protein synthesis and positively affect muscle function and exercise. Studies have previously examined athletes' attitudes towards dietary supplements, but few studies have examined the attitude towards protein supplements in people who have weight training as a hobby.     Aim: The study aims to investigate the attitude to the use of dietary supplements in the form of protein (protein powder, bars). The study will also examine the protein intake of users and non-users of protein supplements.   Material and method: The study consisted of a web-based questionnaire and a diet registration. The recruitment was carried out via a Facebook group that focuses on exercise and health.   Results: A total of ten people participated in the diet registration. There was underreporting of energy intake in all diet registrations, which affects the credibility of the results. There was some difference in protein intake between users and non-users of protein supplements, and non-users of protein supplements consumed more animal products than users. A total of 26 people answered the web formula questionnaire from 18 years up to 50 years old and trained at least three times per week, the response rate varied as there were open ended questions. Intake of protein supplements is largely due to the fact that you need to get extra protein and for those who choose to abstain, it was more about they got enough from their everyday diet.     Conclusion: Despite the uncertainty in reported data on energy intake, dietary records show that users of protein supplements largely rely on protein supplements to cover protein requirements, and the difference in consumption of different types of food groups was primarily animal products. The reason for refraining from protein supplements is because of the cost and its effect.

Traditional weight loss interventions based on the principle “eat less, move more” often lead to weight regain in the long-term. The Health-At-Every-Size® (HAES®) is an alternative intervention that focuses on self-acceptance, intuitive eating, and physical activity for overall well-being. However, evidence on the effectiveness of HAES® in terms of weight loss remains sparse and the existing systematic reviews did not compare the short-term versus long-term effects. The aim of this systematic review was to assess the effectiveness of HAES® on short- and long-term weight loss in people with obesity and overweight. Five scientific databases were searched and 11 papers met the inclusion criteria. These studies were conducted in Canada, United States, Brazil, and the United Kingdom, only with female participants, and in a group-setting. Six out of ten studies with short-term follow-ups (&lt;1y) and four out of seven studies with long-term follow-ups (&gt;1y) reported significant weight reductions in the HAES®-group compared to the pre-intervention baseline. There were no consistent weight reduction effects when HAES® was compared to control groups (waiting list, social support, or traditional dieting). Interestingly, some studies found significant benefits of HAES® on health-outcomes, eating behaviors, or psychological functioning. In conclusion, there is only modest evidence that HAES® facilitates weight loss short-term or long-term. However, there are behavioral and psychological benefits of HAES®, which suggests that combining this method with traditional weight loss interventions could result in optimal outcomes.

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Högt saltintag har traditionellt kopplats till ökad risk för hypertoni, särskilt bland vissa grupper. I detta arbete utforskas relationen mellan saltintag och blodtryck genom en systematisk litteraturgenomgång av randomiserade kontrollerade studier, med fokus på friska individer. Syftet är att utvärdera om och i vilken omfattning saltkonsumtion påverkar blodtrycksnivåerna hos denna population. Studien bygger på litteratursökning i PubMed där relevanta artiklar identifieras med hjälp av sökorden ((high-salt) OR (high-sodium)) AND ((hypertension) OR (blood pressure) AND (healthy). En analys av 17 studier visar att effekten av saltintag på blodtrycket är försumbar eller obefintlig hos friska individer. Dessa resultat betonar behovet av att skilja mellan olika grupper avseende kostrekommendationer och pekar på att individuella skillnader, inklusive saltkänslighet, kan vara avgörande. Diskussionen lyfter fram komplexiteten i förhållandet mellan salt och blodtryck och det är svårt att dra slutsatser om de långsiktiga effekterna av en hög saltkonsumtion. Det understryker att vikten av ytterligare forskning för att klargöra sambandet mellan saltkonsumtion och kardiovaskulär hälsa över olika populationer. / High salt intake has traditionally been linked to an increased risk of hypertension, particularly among certain groups. In this work, the relationship between salt intake and blood pressure is explored through a systematic literature review of randomized controlled trials, focusing on healthy individuals. The aim is to evaluate whether and to what extent salt consumption affects blood pressure levels in this population. The study is based on a literature search in PubMed where relevant articles are identified using the search terms ((high-salt) OR (high-sodium)) AND ((hypertension) OR (blood pressure) AND (healthy)). An analysis of 17 studies shows that the effect of salt intake on blood pressure is negligible or nonexistent in healthy individuals. These results emphasize the need to differentiate between different groups regarding dietary recommendations and point out that individual differences, including salt sensitivity, may be crucial. The discussion highlights the complexity of the relationship between salt intake and blood pressure, and it is difficult to draw conclusions about the long-term effects of high salt consumption. It underlines the importance of further research to clarify the relationship between salt consumption and cardiovascular health across different populations.