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Introduction: Cardiometabolic syndrome is considered a chronic low-grade inflammatory condition that affects various organs and tissues. Individuals with type 2 diabetes mellitus (T2DM) and obesity are at an increased risk for developing the cardiometabolic syndrome and have greater rates of cardiovascular disease (CVD). These conditions are also associated with increased systemic and local inflammation and greater expression of pro-inflammatory markers such as monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), and interleukin 1β (IL-1β) in many tissues. The heart is adversely affected by the inflammation and metabolic changes induced by diabetes and obesity. Nuclear transcription factor kappa B (NF-κB) activity is known to be related to inflammation and cytokine production. However, there is limited information on whether NF-κB signaling and inflammation play a role in early cardiac pathogenesis related to obesity and diabetes and whether lifestyle changes known to prevent or treat these diseases are effective in the heart. Purpose: Therefore, the purpose of this study was to compare the effect of exercise (EX) and caloric restriction (CR) to alter NF-κB signaling, inflammation, and markers of cardiac dysfunction in the heart of 20-week old Otsuka Long Evans Tokushima (OLETF) rats. Methods: Hearts of male 20 week old OLETF rats from a previous study (Crissey et al., 2014) were collected for gene expression (RT-PCR), NF-κB activity, and markers of inflammation and immune cell infiltration. Results: There were no significant differences detected in markers of cardiac dysfunction including, α-MHC, β-MHC, ANP, BNP, COL1, COL3 (all p>0.05). Second, 1-way ANOVA showed that there was trend for an overall effect of group (p=0.07) on NF-κB activation where CR tended to be greater compared to SED and WR (p=0.06). Finally, there were no significant differences between groups in inflammatory and immune cell markers; CD4, F4/80, CD68, IL-1β, MCP-1, TGFB1, and TNF-α (all p>0.05). Conclusion: This study shows that at 20 weeks, a time when OLETF animals exhibit characteristics of the metabolic syndrome such as hypertension, mild obesity, and increased insulin resistance, EX and CR do not reduce markers of cardiac dysfunction and inflammation, potentially because inflammation does not influence the heart at this early time period in the development of the disease. Further, the trend of greater NF-κB activity in CR compared to EX and SED, needs further exploration.

Cardiovascular diseases are the leading cause of death in most industrialised countries and in developing countries the trend in cardiovascular-related deaths is increasing. World-wide, type 2 diabetes mellitus (T2DM) is an emerging cause of disability and premature death. Both these conditions are closely associated with the consumption of energy-dense foods and food products that are poor in nutrients, as well as with a sedentary lifestyle. Pharmacological and surgical interventions can improve the outcome and delay the progression of the disease, but in terms of population-level prevention there is no substitute for the adoption of a healthy lifestyle. SETTING The underlying studies were conducted in Västerbotten (the VIP study), and in Norrbotten and Västerbotten combined (the MONICA Project). Norrbotten andVästerbotten are the two northernmost counties in Sweden. Since the mid-1980sthe prevalence of cardiovascular disease has decreased and diabetes rates haveremained stable in this region, despite of an unbroken trend of increasing body weight. OBJECTIVE The aim of this thesis is to describe changes in reported dietary habits, estimatetheir relative importance as risk factors for diabetes and cardiovascular disease, and finally to identify lifestyle components as potential targets for intervention. RESULTS The first paper describes changes in self-reported food consumption between 1986 and 1999. During this period, the population in question switched from products with high saturated fatty acid content (e.g. milk containing 3% fat, butter) to foods containing less saturated fat (e.g. milk containing 1.5% fat, vegetable oil, low-fat margarine); pasta and rice were consumed more often, and potatoes were consumed less. Convenience foods (e.g. hamburgers, snacks, sweets) became more popular, whilst traditional dishes (e.g. potato dumplings, black pudding, blöta) decreased in popularity. Fruit and vegetable intake remained low. In paper two we study the effects of these changes in food intake on the risk of developing T2DM using body fat distribution as an early indicator. Increased consumption of convenience foods was associated with unfavourable changes (smaller hip circumference and larger waist circumference), whereas the increased consumption of vegetable oil and pasta was associated with low-risk fat distribution. In the third paper we report studies on the association between fat consumption and T2DM. We used the pattern of fatty acids in the membranes of red blood cells as a marker of fat intake. In addition to confirming earlier findings (markers of the intake of saturated fat are associated with increased risk of T2DM and markers of unsaturated fat are associated with reduced T2DM risk), we also identified associations between two markers of milk-derived saturated fat intake and enterolactone, a biomarker of dietary fibre intake, and the risk of developing myocardial infarction. Our results indicate that moderately high levels of enterolactone intake in men are associated with lower risk of experiencing myocardial infarction. Manuscript 5 ranks education level, physical activity, smoking status, and self-reported intake of dietary fibre and fatty acids according to their effects on body fat distribution. Increased levels of physical activity, a higher education level and a reduced intake of saturated fat from meat were ranked as the most strongly associated factors in both men and women. Increased intake of dietary fibre from grains in women, and increased intake of dietary fibre from fruits and vegetables in men, was also inversely associated with average waist circumference. CONCLUSION Both questionnaire-based and biological markers of the risk of developing diabetes or cardiovascular disease have been identified. Based on available population level measurements, reduced consumption of convenience foods, increased consumption of whole-grain products, fruits and vegetables, vegetable oil and pasta as well as increased physical activity are potential goals for interventions in northern Sweden.