Background Obesity is increasing worldwide and is a major contributor to morbidity and mortality. Notably, abdominal (central) obesity carries a high risk of obesity-related diseases, while peripheral fat accumulation can act in a protective manner. A redistribution of fat from peripheral to central depots is seen after the menopause and is associated with an increasing prevalence of diabetes and cardiovascular disease. A key mediator may be ectopic fat accumulation in the liver. Our hypothesis was that a Palaeolithic-type diet (PD) consumed ad libitum improves body composition and metabolic risk markers, including liver fat and insulin sensitivity, in obese postmenopausal women. Methods In study I the study subjects (n=10) used a PD during 5 weeks. In study II and III (n=70) the effect of a Palaeolithic-type diet (PD) was compared to a diet according to the Nordic Nutrition Recommendations diet (NNR) during a 2-year randomized clinical trial (RCT). Food records and nitrogen excretion in urine validated food intake. Anthropometric measurements were performed in a standardized manner. Body composition was calculated using Dual Energy X-ray Absorptiometry (DXA). Total energy expenditure was calculated by accelerometry (Actiheart®) in combination with indirect calorimetry. Liver and muscle fat content was estimated by magnet resonance spectroscopy (1H-MRS). Insulin sensitivity was measured either with hyperinsulinemic euglycemic clamps (paper I) or oral glucose tolerance tests (OGTTs) (paper III). Results In study I a significant weight loss, linked to improved lipid and blood pressure levels, was associated with a 49% decrease in liver fat. Concomitantly, hepatic insulin sensitivity improved, while peripheral insulin sensitivity (and muscle fat) was unaltered. In study II/III both groups had a significant and sustained weight loss after 2 years. The PD was more effective than the NNR diet regarding loss of weight and fat mass after 6 months, but not after 24 months. Serum triglyceride levels were significantly lower at 24 months in the PD group. Liver fat decreased throughout the study in both groups. Hepatic insulin sensitivity improved during the first 6 months of the study, while peripheral insulin sensitivity did not change. Hepatic insulin sensitivity was associated with liver fat at baseline, but not during the diet intervention. Energy expenditure did not change in any of the study groups. Conclusion Ad libitum diets can have sustained beneficial effects on weight and body composition in obese postmenopausal women, a PD being more effective on short-term than a diet according to the NNR. This is associated with a reduction in liver fat that may reduce the risk of future diabetes and cardiovascular disease. Further studies are needed in order to explore the association between liver fat and metabolic dysfunction, including insulin sensitivity.

Nutrition status during adolescent pregnancy and childbearing is a complex, multifaceted condition that can impact the health status of the teen mother and her baby. Adolescent mothers are at higher risk for low birth weight infants because of the unique dietary requirements needed to accommodate for both the growth needs of the adolescent mother and her unborn child. The purpose of this research was to examine dietary interventions that have the greatest effect on fetal birth weight outcomes in adolescent mothers. Secondly, this study explored dietary nutrients effective in reducing the likelihood of complications commonly associated with low birth weight infants in adolescent pregnancy. A systematic literature review was conducted from the following online databases: Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medical Literature On-line (MEDLINE), Education Resources Information Center (ERIC), and PsycInfo. Initial search terms included 'adolescent', 'nutrition', 'diet', and 'prenatal'. Further search items included 'weight' and 'outcome'. Selected articles included those published between 2000-2013, written in English, and peer-reviewed. Significant evidence supported positive birth weight outcomes for dietary supplementation with zinc and calcium, and BMI-specific weight gains for adolescent pregnancy. No significant evidence was provided on the effect of iron and fatty acid composition on birth weight outcomes. Results for other dietary interventions and their effects on fetal birth weight were either inconclusive or absent. Discovering dietary interventions that work best in prenatal care of adolescent populations will allow for more individually-tailored, dietary specific interventions to be developed to combat the prevalence of low fetal birth weight infants in adolescent pregnancy.

No description available.

Übergewicht und Adipositas führen zu Insulinresistenz und erhöhen deutlich das Risiko für die Entwicklung von Typ-2-Diabetes und kardiovaskulären Erkrankungen. Sowohl Adipositas als auch die Suszeptibilität gegenüber Diabetes sind zu einem erheblichen Teil genetisch determiniert. Die relevanten Risikogene, deren Interaktion mit der Umwelt, insbesondere mit Bestandteilen der Nahrung, und die Pathomechanismen, die zur Insulinresistenz und Diabetes führen, sind nicht vollständig aufgeklärt. In der vorliegenden Arbeit sollte durch Genexpressionsanalysen des weißen Fettgewebes (WAT) und der Langerhansschen Inseln die Entstehung und Progression von Adipositas und Typ-2-Diabetes untersucht werden, um relevante Pathomechanismen und neue Kandidatengene zu identifizieren. Zu diesem Zweck wurden Diät-Interventionsstudien mit NZO- und verwandten NZL-Mäusen, zwei polygenen Mausmodellen für das humane metabolische Syndrom, durchgeführt. Eine kohlenhydrathaltige Hochfett-Diät (HF: 14,6 % Fettanteil) führte in beiden Mausmodellen zu früher Adipositas, Insulinresistenz und Typ 2 Diabetes. Eine fettreduzierte Standarddiät (SD: 3,3 % Fettanteil), welche die Entstehung von Adipositas und Diabetes stark verzögert, sowie eine diabetesprotektive kohlenhydratfreie Hochfett-Diät (CHF: 30,2 % Fettanteil) dienten als Kontrolldiäten. Mit Hilfe der Microarray-Technologie wurden genomweite Expressionsprofile des WAT erstellt. Pankreatische Inseln wurden durch laserbasierte Mikropräparation (Laser Capture Microdissection; LCM) isoliert und ebenfalls hinsichtlich ihres Expressionsprofils analysiert. Differenziell exprimierte Gene wurden durch Real-Time-PCR validiert. Im WAT der NZO-Maus bewirkte die HF-Diät eine reduzierte Expression nukleärer Gene der oxidativen Phosphorylierung und von lipogenen Enzymen. Dies deutet auf eine inadäquate Fettspeicherung und -verwertung in diesen Tieren hin. Die Reduktion in der Fettspeicherung und -oxidation ist spezifisch für das adipöse NZO-Modell und konnte bei der schlanken SJL Maus nicht beobachtet werden, was auf eine mögliche Beteiligung an der Entstehung der Insulinresistenz hinweist. Zusätzlich wurde bestätigt, dass die Expansion des Fettgewebes bei der adipösen NZO-Maus eine zeitlich verzögerte Infiltration von Makrophagen in das WAT und dort eine lokale Immunantwort auslöst. Darüber hinaus wurde die Methode der LCM etabliert und zur Gewinnung hochangereicherter RNA aus den Langerhansschen Inseln eingesetzt. In erstmalig durchgeführten genomweiten Expressionsanalysen wurde zu einem frühen Zeitpunkt in der Diabetesentwicklung der Einfluss einer diabetogenen HF-Diät und einer diabetesprotektiven CHF-Diät auf das Expressionsprofil von pankreatischen Inselzellen verglichen. Im Gegensatz zum WAT bewirkt die diabetogene HF-Diät in Inselzellen einerseits, eine erhöhte Expression von nukleären Genen für die oxidative Phosphorylierung und andererseits von Genen, die mit Zellproliferation assoziiert sind. Zudem wurden 37 bereits annotierte Gene identifiziert, deren differenzielle Expression mit der Diabetesentwicklung korreliert. Das Peptidhormon Cholecystokinin (Cck, 11,8-fach erhöht durch die HF) stellt eines der am stärksten herauf regulierten Gene dar. Die hohe Anreicherung der Cck-mRNA in Inselzellen deutet auf eine bisher unbekannte Funktion des Hormons in der Regulation der Inselzellproliferation hin. Der Transkriptionsfaktor Mlxipl (ChREBP; 3,8-fach erniedrigt durch die HF) stellt in Langerhansschen Inseln eines der am stärksten herunter regulierten Gene dar. Ferner wurde ChREBP, dessen Funktion als glucoseregulierter Transkriptionsfaktor für lipogene Enzyme bislang in der Leber, aber nicht in Inselzellen nachgewiesen werden konnte, erstmals immunhistochemisch in Inselzellen detektiert. Dies deutet auf eine neue, bisher unbekannte regulatorische Funktion von ChREBP im Glucosesensor-Mechanismus der Inselzellen hin. Eine durchgeführte Korrelation der mit der Diabetesentwicklung assoziierten, differenziell exprimierten Inselzellgene mit Genvarianten aus humanen genomweiten Assoziationsstudien für Typ-2-Diabetes (WTCCC, Broad-DGI-T2D-Studie) ermöglichte die Identifizierung von 24 neuartigen Diabetes-Kandidatengenen. Die Ergebnisse der erstmals am polygenen NZO-Mausmodell durchgeführten genomweiten Expressionsuntersuchungen bestätigen bisherige Befunde aus Mausmodellen für Adipositas und Diabetes (z.B. ob/ob- und db/db-Mäuse), zeigen in einigen Fällen aber auch Unterschiede auf. Insbesondere in der oxidativen Phosphorylierung könnten die Ergebnisse relevant sein für das Verständnis der Pathogenese des polygen-bedingten humanen metabolischen Syndroms. / Overweight and obesity cause insulin resistance and increase the risk of developing type 2 diabetes and cardiovascular diseases. Both, obesity and susceptibility to diabetes, are to a major part genetically predisposed. The relevant genes, their interaction with the environment – especially with food components – and the pathomechanisms causing insulin resistance and diabetes are not fully known yet. In the present study the development and progression of obesity and type 2 diabetes should be investigated by the means of gene expression analyses of the white adipose tissue (WAT) and the islets of Langerhans to identify underlying pathomechanisms and new causative candidate genes. For this purpose diet intervention studies on NZO- and related NZL-mice – two polygenic mouse models for the human metabolic syndrome – were performed. A carbohydrate containing high fat-diet (HF: 14.6 % fat) caused early obesity, insulin resistance and type 2 diabetes in both mouse models. A fat reduced standard chow (SD: 3.3 % fat) which strongly delayed the onset of obesity and diabetes, and a diabetes protective carbohydrate free high fat-diet (CHF: 30.2 % fat) served as control diets. Using microarray technology genome wide expression profiles of the WAT were generated. Pancreatic islets were isolated by the means of laser capture microdissection (LCM) and expression profiles of them were created, too. Differentially expressed genes were validated by quantitative real time PCR. The HF-diet reduced the expression of nuclear genes of the oxidative phosphorylation and lipogenic enzymes in the WAT of the NZO-mouse. This suggests an inadequate storage and utilization of fat in these animals. This is specific for the obese NZO-model and wasn’t observed for the lean SJL-mouse, indicating a role in the development of insulin resistance. Additionally, there was proof that the enlargement of the WAT triggers a retarded infiltration of macrophages into the WAT and there a local immune response. Moreover, the LCM technique was established and used for the isolation of highly enriched RNA from islets of Langerhans. For the first time the influence of carbohydrates in a high fat-diet on the expression profile of pancreatic islets was investigated by the use of genome wide expression analyses at an early time point at the onset of diabetes. Contrary to the WAT the diabetogenic HF-diet in islets cells increased the expression of both nuclear genes coding for the oxidative phosphorylation and genes associated with cell proliferation. Furthermore 37 already annotated genes correlated with diabetes progression were identified. The peptide hormone cholecystokinin (Cck: 11.8-fold enriched by the HF-diet) is one of the most up-regulated genes. The strong enrichment of Cck-mRNA in islets suggests a previously unknown function of the hormone in the regulation of the islet cell proliferation. The transcription factor ChREBP (Mlxipl: 3.8-fold reduced by the HF-diet) is one of the most down-regulated genes in the islets of Langerhans. Moreover, ChREBP, which has been already identified as a glucose regulated transcription factor for lipogenic enzymes in the liver but not in islets of Langerhans, was detected for the first time in islet cells, using immunohistochemistry. This points to an until now unknown regulatory function of ChREBP in the glucosesensor mechanism of the islet cells. Correlation of the differentially expressed genes associated with diabetes progression with gene variants from human genome wide association studies for type 2 diabetes (WTCCC, Broad-DGI-T2D-study) made the identification of 24 new diabetes candidate genes possible. The results of the genome wide expression analyses, which were done for the first time on a polygenic mouse-model, corroborated previous results for monogenic mouse-models for obesity and diabetes (e.g. ob/ob- and db/db-mice), however also demonstrated differences in some instances. Especially the results concerning the oxidative phosphorylation could be relevant for the comprehension of the pathogenesis of the polygenic human metabolic syndrome.

No description available.

La vitamine K est reconnue pour son rôle dans la coagulation sanguine. Les apports alimentaires de cette vitamine influencent la stabilité de l’anticoagulothérapie à la warfarine sodique. Une intervention visant à augmenter de ≥ 150 μg/j les apports alimentaires de vitamine K a été développée au sein du laboratoire de Guylaine Ferland. Les données préliminaires d’un essai clinique randomisé contrôlé de 24 semaines ont montré que les participants ayant suivi la stratégie alimentaire portant sur la vitamine K ont présenté une anticoagulothérapie plus stable, comparativement aux participants du groupe témoin. Cette stratégie a été décrite afin de fournir les informations nécessaires à son application en pratique clinique. Les anticoagulants demeurent des piliers dans la prévention des évènements thrombotiques notamment chez certaines personnes atteintes de maladies cardiovasculaires (MCV). Parmi les MCV, les maladies du coeur [particulièrement la maladie coronarienne (MC)] sont les plus répandues. La MC peut accélérer le développement de troubles cognitifs avec l’âge, et ce déclin cognitif relève en grande partie de l’atteinte vasculaire sous-jacente. La vitamine K constitue un nutriment d’intérêt pour le système vasculaire et la cognition au cours du vieillissement et aurait le potentiel d'atténuer les effets néfastes de la MC sur le cerveau. Une étude pilote d’intervention de 12 semaines examinant l’impact d’un supplément de 500 μg/j de vitamine K sur les fonctions cognitives et vasculaires d’individus atteints de MC stable a été développée. Ce projet a été implanté à l’Institut de Cardiologie de Montréal en mai 2022, et à ce jour, quatre participants ont complété l’intervention. À terme, cette étude permettra d’obtenir une évaluation préliminaire des bénéfices associés à la supplémentation de vitamine K sur la cognition et à recueillir des preuves suffisantes justifiant la planification d’une étude de plus grande envergure au sein de cette population. / Vitamin K is known for its role in blood coagulation. Dietary intakes of this vitamin influence the stability of warfarin anticoagulation therapy. An intervention aiming to increase dietary vitamin K intakes by ≥ 150 μg/d was developed in Guylaine Ferland's laboratory. Preliminary data from a 24-week randomized controlled trial showed that participants who followed the vitamin K dietary strategy had more stable anticoagulation therapy compared to participants in the control group. This strategy was described to provide the necessary information for its application in clinical practice. Anticoagulants remain mainstays in the prevention of thrombotic events notably in certain people with cardiovascular disease (CVD). Among CVD, heart disease [particularly coronary heart disease (CHD)] is the most prevalent. Coronary heart disease can accelerate the development of cognitive impairment with age, and this cognitive decline is largely a consequence of the underlying vascular impairment. Vitamin K is a nutrient of interest for the vascular and nervous systems during aging, and has the potential to mitigate the adverse effects of CHD on the brain. A 12-week pilot study examining the impact of a 500 μg/d vitamin K supplement on cognitive and vascular functions in individuals with stable CHD was developed. This project was implemented at the Montreal Heart Institute in May 2022, and to date, four participants have completed the intervention. This study will provide a preliminary assessment of the benefits associated with vitamin K supplementation on cognition and provide sufficient evidence to justify the planning of a larger study in this population.

The obesity epidemic is a global health concern. In the United States alone, 68.5% of adults are categorized as overweight or obese; of these, 35.1% are considered obese. Obesity is a leading cause of morbidity and mortality from diabetes and cardiovascular disease, two diseases adversely affecting minority groups such as Mexican Americans. Yet, a modest 5% decrease in weight, through changes in diet and physical activity, can help control type 2 diabetes. The current study extracted the dietary data and selected outcome variables from Beyond Sabor, a 12 week intervention conducted in the Lower Rio Grande Valley, Texas, a predominantly Mexican American disadvantaged community. Social Cognitive Theory, guided the design of this culturally tailored intervention. Community resources and natural helpers emerged through the utilization of community based participatory research methods. Study participants (n= 1,273) were recruited from local food bank sites and randomized into treatment and control groups. The treatment group received 12 weekly sessions focusing on healthier eating habits, cooking methods, and physical activity. The control group received 6 nutrition education sessions on similar topics. The study measured changes in several food groups including consumption of soda, fruit juice, and fruit and vegetables. A repeated measures Analysis of Variance was employed to determine changes in treatment and control groups from baseline, post intervention and 40 week follow up. The results showed a significant decrease in soda (F= 8.48, p< .001) and fruit juice (F= 3.12, p= .045) consumption for both groups, with a particular decrease in soda for the treatment group. In addition, there was a significant increase in fruit (F=15.32, p< .001) and vegetable (F=3.16, p= .04) consumption in both groups. The outcome variables selected were weight, body mass index (BMI), and fasting plasma glucose (FPG). There were significant changes for all three variables over time. The intervention resulted in changes in dietary behaviors that ultimately led to changes in weight, BMI, and FPG. It is evident from the current study, that the use of community based helpers facilitated changes in food habits. This study serves as a prognosticator for future interventions.

Background Obesity, in particular abdominal adiposity, is associated with elevated fatty acids and pro-inflammatory adipokines, which are linked to ectopic fat storage and insulin resistance. During menopause, there is a redistribution of fat from the peripheral to abdominal depots. This transition is associated with an increased risk of type 2 diabetes and cardiovascular diseases. We hypothesized that a Paleolithic diet, with high proportions of lean meat, fish, vegetables, fruits, and oils, but devoid of dairy products and cereals, might have long-term beneficial effects on inflammation, fat metabolism, and circulating fatty acids. These effects might potentially reduce the risk of metabolic complications in postmenopausal women that are obese.  Methods Postmenopausal women with obesity were studied before, after six months, and after 24 months of one of two specified ad libitum diets. One diet was a Paleolithic diet, in which approximately 30% of the total energy (E%) was protein, 30 E% was fat, and 40 E% was carbohydrate. The other diet was a prudent control diet, consistent with Nordic Nutrition recommendations of 15 E% protein, 25 E% fat, and 55 E% carbohydrate. Dietary intakes of polyunsaturated fatty acids and protein were validated objectively by measuring circulating and urinary biomarkers. Anthropometrics and diet reports were analyzed, and abdominal subcutaneous fat samples were evaluated for the expression of proteins key in inflammation and fat metabolism and for lipoprotein lipase mass and activity. In addition, blood samples were analyzed to determine concentrations of specific serum proteins, serum lipids, and the fatty acids carried in cholesterol esters. Results The Paleolithic diet group reported reduced intakes of saturated fatty acids and carbohydrates and elevated intakes of protein and unsaturated fatty acids, compared to baseline. The elevated intakes of polyunsaturated fatty acids and protein were objectively verified for this group. After 24 months, both diets were found to have beneficial effects on the expression of inflammation-related genes in adipose tissue and pro-inflammatory factors in the circulation. Compared to the control group, the Paleolithic diet group exhibited more pronounced reductions of circulating cardiometabolic risk factors, including the ratio of triglycerides to high density lipoprotein, lipogenic index, specific fatty acids, and indices of desaturase activities. After six months, the Paleolithic group also exhibited more pronounced reductions in lipogenesis-promoting factors, including the expression of key proteins in fat synthesis, the activity of lipoprotein lipase, and the activity of stearoyl-CoA desaturase 1, compared to the control group. Conclusion Long-term weight loss in postmenopausal obese women was accompanied by reductions in low-grade inflammation in adipose tissue and in the circulation. In addition, a Paleolithic diet, with a high content of unsaturated fatty acids and a low content of refined carbohydrates, appeared to provide greater reductions in cardiometabolic risk factors associated with insulin resistance and lipogenesis, compared to a prudent control diet. / Bakgrund De senaste decennierna har förekomsten av övervikt och fetma ökat kraftigt i stora delar av världen. Detta beror på en kombination av olika faktorer såsom specifika gener vilka främjar fettinlagring, men kanske främst ett överintag av energirik mat i kombination med minskad fysisk aktivitet. Fetma och specifikt bukfetma, vilket tilltar hos kvinnor efter klimakteriet (postmenopausala), ökar risken för höjda blodfettsnivåer och låggradig inflammation, vilket kan leda till utveckling av typ 2-diabetes samt hjärt- och kärlsjukdomar. Kost och viktnedgång är avgörande för bibehållen hälsa och av stort intresse är att urbefolkningar runt om i världen har låg förekomst av fetma, diabetes, hjärt- och kärlsjukdom, troligtvis kopplat till olika livsstilsfaktorer som högre fysisk aktivitet samt kostfaktorer.  Syfte Vårt syfte var att undersöka metabola förändringar i fettväv och cirkulation hos postmenopausala kvinnor med fetma kopplat till en 24 månaders paleolitisk kostintervention. Den paleolitiska kosten, som ingick i studien består av en hög andel magert kött, fisk, grönsaker, frukt, nötter, oliv- och rapsolja och där mjölkprodukter och spannmål är uteslutna. Vår hypotes var att en paleolitisk kost med hög andel protein och omättade fettsyror har fördelaktiga långtidseffekter på inflammation, fettmetabolism och cirkulerande fettsyror jämfört med en kost baserad på Nordiska näringsrekommendationer med ett högt intag av kolhydrater. Metoder Postmenopausala kvinnor med fetma studerades före, vid sex månader och efter 24 månaders intag, utan energirestriktioner, av antingen en paleolitisk kost eller en kost enligt Nordiska näringsrekommendationer. Kroppsmätningar, kostregistreringar, genuttryck av nyckelproteiner i inflammation och fettmetabolism i fettväv samt koncentrationer av blodfetter, specifika proteiner och fettsyror bestämdes i plasma. Resultat I linje med rekommendationerna så rapporterade gruppen som åt den paleolitiska kosten ett minskat intag av mättat fett och kolhydrater samt ett ökat intag av protein och omättat fett jämfört med baslinjenivåerna. Det ökade intaget av fleromättade fettsyror och protein bekräftades med objektiva mätmetoder. Efter 24 månaders intervention uppvisade båda grupperna en jämförbar viktnedgång och en minskning av flertalet proinflammatoriska faktorer i såväl fettväv som i cirkulation. Den grupp som åt paleolitisk kost uppvisade en kraftigare reduktion av cirkulerande kardiometabola riskfaktorer som index för fettsyntes och desaturaser, specifika fettsyror samt kvoten triglycerider till HDL (high density lipoprotein). Efter sex månader bidrog den paleolitiska kosten också till en mer påtaglig minskning av faktorer involverade i fettinlagring, som uttryck av specifika nyckelproteiner i fettsyntes, aktivitet för lipoprotein lipas och stearoyl-CoA desaturase 1 index jämfört med kontrollkosten. Slutsatser En långvarig viktminskning hos postmenopausala kvinnor med fetma åtföljs av en minskad låggradig inflammation i fettväv och i cirkulation. En paleolitisk kost med hög andel omättade fettsyror och låga halt kolhydrater är kopplat till en kraftigare minskning av riskparametrar för insulinresistens och nyckelfaktorer för fettinlagring jämfört med en kontrollkost enligt Nordiska näringsrekommendationer.