This MSc. thesis deals with dissecting the link between memory, genetics, and metabolic syndrome. Memory is a very complex behavioral trait, probably influenced by innumerable factors. For this experiment HXB/BXH rat recombinant inbred lines (n= 30) and their parental strains (n=2) were used to be trained in the hippocampus dependant spatial learning task called Allothetic Active Place Avoidance. Rats were to memorize sector of a rotating circular arena, which they were to avoid, being motivated by receiving an electric shock upon entering the forbidden sector (4 training sessions; shock sector on the North, 1 retrieval session (no shock), and 3 reversal sessions, to-be-avoided sector facing South; each session 20-min long, retrieval 10-min). Control experiments to exclude impact of motor or sensory abnormalities were run in a form of open-field test and beam-walking test. Correlation with metabolic phenotypes was conducted in an online database of known HXB/BXH phenotypes (GeneNetwork.org). The results showed that differences in learning were significant between the groups (p<0.05); correlation analysis indicated no putative link between selected traits related to metabolic syndrome and memory in rats. The genetic analysis showed a suggestive locus on chromosome 20 for a learning parameter, and...

Visceral adipose tissue derived serine protease inhibitor (vaspin) or SERPINA12 according to the serpin nomenclature was identified together with other genes and gene products that  were specifically expressed or overexpressed in the intra abdominal or visceral adipose tissue  (AT) of the Otsuka Long-Evans Tokushima fatty rat. These rats spontaneously develop visceral  obesity, insulin resistance, hyperinsulinemia and ‐glycemia, as well as hypertension and thus represent a well suited animal model of obesity and related metabolic disorders such as type  2 diabetes.  The follow-up study reporting the cloning, expression and functional characterization of  vaspin suggested the great and promising potential of this molecule to counteract obesity induced insulin resistance and inflammation and has since initiated over 300 publications, clinical and experimental, that have contributed to uncover the multifaceted functions and molecular mechanisms of vaspin action not only in the adipose, but in many different cells, tissues and organs. This review will give an update on mechanistic and structural aspects of vaspin with a focus on its serpin function, the physiology and regulation of vaspin expression, and will summarize the latest on vaspin function in various tissues such as the different adipose tissue depots as well as the vasculature, skin, bone and the brain.

Metabolic syndrome (MetS) is a complex condition with a number of interacting genes, epigenetic and environmental factors underlying its pathogenesis. The analysis of genetic component of MetS showed that number of defining parameters of the syndrome is linked to regions of rat chromosome 4. In order to verify these quantitative trait loci (QTL), a double congenic strain was derived with parts of chromosome 4 of spontaneously hypertensive rat (SHR, an inbred MetS model) origin introgressed onto genomic background of congenic Brown Norway strain (BN-Lx). The aim of the proposed thesis is comprise detail genetic mapping of differential segments of the above mentioned double congenic strain BN-Lx.SHR4 and comparison of its metabolic profile under different dietary conditions with varying carbohydrate and fat content. Utilizing DNA sequence and gene expression comparisons, candidate genes or polymorphisms for the MetS aspects and potential nutrigenetic interactions will be identified. Key words: nutrigenetics, experimental models, metabolic syndrome, congenic strain, genotyping, rat

Hjärt- och kärlsjukdom är den vanligaste dödsorsaken i västvärlden och typ 2-diabetes är en av våra största folksjukdomar. De vanligaste riskfaktorerna är fetma, högt blodtryck, höga blodfetter och insulinresistens. En kombination av minst tre av dessa riskfaktorer utgör ett metabolt syndrom, vilket drastiskt ökar risken att drabbas av hjärt- och kärlsjukdom och typ 2-diabetes. Det metabola syndromet orsakas till stor del av osund kosthållning och brist på fysisk aktivitet. Få studier beskriver distriktssköterskans förebyggande koståtgärder för patienter med metabolt syndrom som ännu inte utvecklat hjärt- och kärlsjukdom eller typ 2-diabetes. Syftet med denna studie är att beskriva distriktssköterskans upplevelse av förebyggande koståtgärder för patienter med metabolt syndrom inom primärvården. Detta är en kvalitativ intervjustudie med induktiv ansats, där sex intervjuer med distriktssköterskor med minst sex månaders arbetslivserfarenhet, genomfördes och analyserades enligt kvalitativ innehållsanalys. Distriktssköterskan utgår från patienten i sitt förebyggande arbete gällande kostråd. Patientens motivation är en förutsättning för ett lyckat resultat. Personcentrerad vård eftersträvas, men strukturella hinder som till exempel tidsbrist och otillräckliga riktlinjer om tillvägagångsätt i arbetet försvårar distriktssköterskans förebyggande koståtgärder för patienter med metabolt syndrom. Koståtgärder behöver prioriteras som behandling och mer tid behöver avsättas för hälsofrämjande insatser inom primärvården. / Cardiovascular disease is the leading cause of death in the west and type 2 diabetes is one of our most frequent disease. The most common risk factors are obesity, high blood pressure, high blood lipids and insulin resistance. A combination of at least three of these risk factors constitutes a metabolic syndrome, which drastically increases the risk of cardiovascular disease and type 2 diabetes. The metabolic syndrome is largely caused by unhealthy diets and lack of physical activity. Few studies describe the district nurse's dietary prevention work in patients with metabolic syndrome, who have not yet developed cardiovascular disease or type 2 diabetes. The aim of this study is to describe the district nurse's experience of dietary prevention work in patients with metabolic syndrome in primary health care. This is a qualitative interview study with inductive approach, where six interviews with district nurse’s with at least six months experience of work, were carried out and analyzed according to qualitative content analysis. The district nurse's preventive work is based on the patient. The patient's motivation is a prerequisite for a good result. Person centered care is sought, but structurally barriers, mainly in form of time shortage and inadequate guidelines about the procedures of work, impedes the district nurse's dietary preventive work in patients with metabolic syndrome. Cost advice needs to be priority as treatment and more time needs to be disposed on health promotion in primary care.

Fat tissue plays a main role in the development of the metabolic syndrome. Many components of the metabolic syndrome may be improved by dietary arrangements, including an increased intake of n-3 PUFA. In addition to the positive effect of n-3 PUFA, a possible effect of a higher calcium intake on influencing weight loss and energy metabolism has also been discussed for a long time. In addition to nutritional factors, genetic factors significantly contribute to influencing weight and lipid and glucose metabolism. In study A, 40 obese women were observed during three weeks of weight reduction management. Women were randomly divided into two groups. The first group received yogurt enriched with n-3 PUFA, and the second group consumed yoghurt without the supplementation. The results show that low-dose supplementation with n-3 PUFA in yogurt in combination with a reduced energy intake increases n-3 PUFA content in serum lipids and prevents adverse changes in the composition of FA in serum after a short-term low-calorie diet. In study B, we monitored the influence of n-3 PUFA supplementation on short-term weight management with VLCD in 20 women with severe obesity, who were randomly divided into two groups. The first group received VLCD enriched with n-3 PUFA, the second group VLCD with a placebo. The addition of...

Univerzita Karlova v Praze 1. lékařská fakulta Doktorský studijní program Studijní obor: Experimentální chirurgie MUDr. Filip Thieme Název závěrečné práce Chirurgické modely studia proinflamačního vlivu tukové tkáně v rozvoji aterosklerózy Title Surgical models of the study of the pro-inflammatory effect of adipose tissue in the development of atherosclerosis Typ závěrečné práce Disertační Školitel: doc. MUDr. Jiří Froněk, Ph.D., FRSC Konzultant doc. MUDr. Libor Janoušek, Ph.D. Klinika transplantační chirurgie, IKEM Praha, 2021 Abstract Background: Atherosclerosis is a serious inflammatory systemic disease. Surgery mainly addresses its vascular complications. Conversely, surgery may also lead to the development and acceleration of atherosclerosis, e.g., in a living kidney donor. This would especially be the case in a donor who meets internationally recognized donation criteria but suffers from metabolic syndrome. The effort to refine assessments of living kidney donors in terms of eliminating the risk of developing atherosclerosis is a long-term project. Our aim is to determine risk factors for living kidney donors and to prevent long-term complications after donation. Collecting tissue from a living donor involves not oly subcutaneous tissue (SCAT) but also visceral (VAT) and perivascular tissue (PVAT),...

Childhood obesity and its sequelae are a major public health problem in both the USA and globally. This review will focus on a systems medicine approach to obesity. Systems medicine is an integrative approach utilizing the vast amount of data garnered from "omics" technology and integrating these data with conventional pathophysiology as well as diverse environmental factors such as diet, exercise, community dynamics and the intestinal microbiome. Omics technology includes genomics, epigenomics, metagenomics, metabolomics and proteomics. In addition to unraveling etiology, the goals of a systems medicine approach are to provide actionable and evidenced-based clinical approaches. In the case of childhood obesity, an additional goal is characterizing measureable risk factors/biomarkers for obesity at the earliest possible age and devising age-appropriate optimal intervention strategies. It is also important to establish the age at which interventions could be critical. As discussed below, it is possible that some of the pathophysiological and epigenetic changes resulting from childhood obesity could become more irreversible the longer the obesity remains untreated.

Metabolic disorders are commonly associated with obesity, a condition where excess caloric intake leads to massive adipose tissue (AT) expansion and eventual dysfunction. When adipose tissue loses its ability to store excess energy properly, lipids accumulate in non-adipose tissues such as liver, and muscle. This ectopic lipid deposition is a significant risk factor in the development of a collection of disorders described as metabolic syndrome. While metabolic syndrome is typically linked with obesity, patients who have an inability to develop adipose tissue depots (lipodystrophy) develop similar clinical outcomes. There is evidence that aberrant mTORC1 signaling may occur in both settings, and may be a factor that contributes to adipose dysfunction. I find that adipocyte specific loss of Raptor, a key mTORC1 subunit, leads to progressive lipoatrophy, and associated metabolic dysfunction including AT inflammation, hepatosteatosis, and insulin resistance. Interestingly, inhibition of autophagy, a pathway upregulated during Raptordeletion, prevents lipoatrophy but does not protect from ectopic lipid deposition and AT inflammation. These results suggest that outputs of mTORC1 in adipocytes individually regulate adipocyte storage capacity, and AT health. Furthermore, ablation of the amino acid sensing RagGTPases, thought to be necessary for mTORC1 activity, does not phenocopy Raptor KO, suggesting RagGTPase independent functions of mTORC1 in adipocytes. RagA/B deletion, however, did consistently increase Ucp1 expression in WAT, indicating a possible noncanonical role of the Rags in regulating Ucp1. Overall, these studies advance our understanding of regulation of adipose tissue metabolism, and shed light on previously unstudied nutrient specific signaling pathways in adipocytes.

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Exercise has been considered a cornerstone of diabetes prevention and treatment for decades, but the benefits of resistance training are less clear. Nineteen non-diabetic subjects (10 metabolic syndrome, 9 sedentary controls) underwent 8 weeks of supervised resistance training. After training, strength and V̇ O2max increased by 10% in both groups. Percent body fat decreased in subjects with the metabolic syndrome. Additionally, lean body mass increased in both groups (p<0.05). Expression of glucose transporter protein-4 (GLUT4), the principle insulin-responsive glucose transporter, increased significantly in both groups. 5-adenosine monophosphateactivated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) expression increased in both groups, indicating increased protein synthesis and mitochondrial biogenesis. Markers of insulin resistance measured by a euglycemic hyperinsulinemic clamp did not improve in subjects with the metabolic syndrome but increased significantly in control subjects (13%). Resistance training upregulates intracellular signaling pathways that may be beneficial for ameliorating the metabolic syndrome.