Markku Ahotupa

Markku Ahotupa
University of Turku | UTU · Department of Physiology

PhD

About

182
Publications
12,083
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7,399
Citations
Citations since 2016
10 Research Items
1811 Citations
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300

Publications

Publications (182)
Article
Objective Oxidation of low-density lipoprotein (LDL) may promote atherosclerosis, whereas the reverse transport of oxidized lipids by high-density lipoprotein (HDL) may contribute to atheroprotection. To provide insights into the associations of lipoprotein lipid oxidation markers with lipoprotein subclasses at the population level, we investigated...
Book
Cholesterol has ruled the history of atherosclerosis for decades, and the transport of cholesterol by lipoproteins has become a cornerstone of our view of etiology of the disease. Discovery of the lipoprotein-specific transport of lipid oxidation products (LOP) has opened a new and exciting area in atherosclerosis research by revealing strong conne...
Article
A gain-of-function polymorphism in human neuropeptide Y (NPY) gene (rs16139) associates with metabolic disorders and earlier onset of type 2 diabetes (T2D). Similarly, mice overexpressing NPY in noradrenergic neurons (OE-NPY(DBH)) display obesity and impaired glucose metabolism. In this study, the metabolic syndrome -like phenotype was characterize...
Article
Full-text available
Plasma lipoproteins contain variable amounts of lipid oxidation products (LOP), which are known to impair normal physiological functions and stimulate atherosclerotic processes. Recent evidence indicate that plasma lipoproteins are active carriers of LOP, LDL directing transport towards peripheral tissues, and HDL being active in the reverse transp...
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Similar to muscles, the intestine is also insulin resistant in obese subjects and subjects with impaired glucose tolerance. Exercise training improves muscle insulin sensitivity, but its effects on intestinal metabolism are not known. We studied the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT)...
Article
We studied the effects of different types of exercises on the concentrations of oxidised HDL (oxHDLlipids) and LDL lipids (oxLDLlipids), serum lipids, antioxidant potential, paraoxonase and malondialdehyde in endurance runners by performing both a 40-min continuous run (velocity corresponding to 80% VO2max) and a 40-min intermittent run (2-min run,...
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During acute exercise, the concentration of oxidized HDL lipids (ox-HDL) is reported to increase suggesting that HDL may function in decreasing the concentration of oxidized LDL lipids. However, the effect of exercise intervention on the lipid peroxide transport function of HDL is unknown. A randomized controlled trial with sedentary women (N = 161...
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Purpose Physical exercise has cardioprotective functions, which have been partly linked to high-density lipoprotein (HDL), and its functions. We studied the effects of endogenous oxidative stress, induced by acute exhaustive physical exercise, on concentration of oxidized HDL lipids. Methods Twenty-four male national top-level endurance runners, 12...
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Objectives: Oxidative stress (OS) is an essential element in the pathogenesis of Barrett's esophagus (BE) and its transformation to adenocarcinoma (EAC). The state of OS in the proximal stomach of patients with BE and EAC is unknown. Isoprostanes are a specific marker of OS not previously used to determine OS from BE/EAC tissue samples. Patients...
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Oxidative reactions are thought to play a role in the inflammatory condition called fatty liver. It is unclear whether oxidized lipoprotein lipids or proteins are associated with future fatty liver. In the Cardiovascular Risk in Young Finns Study, we determined the circulating levels of LDL and HDL oxidized lipids and studied their associations wit...
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Three independent trials were conducted to evaluate postprandial triglyceride (TG) responses in subjects with different lipid metabolism. The effect of polydextrose (PDX), a soluble non-digestible carbohydrate, on postprandial response was also studied using practically relevant, high fat meal interventions. A total of 19 normolipidemic (average BM...
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Insulin metabolism has been previously linked to oxidized low-density lipoproteins (ox-LDL), but corroborating intervention studies are lacking. We investigated whether changes in ox-LDL levels are accompanied by changes in insulin sensitivity in a 32-month life-style intervention study. A 2-month weight reduction was followed by 6-month diet and e...
Article
Paraoxonase-1 (PON1) is suggested to have a role in the antioxidant activity of high-density lipoprotein (HDL). PON1 activity levels are strongly genetically determined by the rs662 polymorphism (PON1 Q192R). To clarify the role of PON1 in lipoprotein oxidation at the population level, we examined the relations between PON1 activity, the rs662 poly...
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Recent reports show that a fatty meal can substantially increase the concentration of oxidized lipids in low density lipoprotein (LDL). Knowing the LDL-specific antioxidant effects of high density lipoprotein (HDL), we aimed to investigate whether HDL can modify the postprandial oxidative stress after a fatty meal. Subjects of the study (n = 71) co...
Article
Nutrition contributes to increased adiposity, but it remains to be determined whether high fat rather than Western diet exacerbates the development of obesity and other characteristics of metabolic syndrome and vascular function. We studied the effects of high fat (45% kcal) diet (HFD) and equal caloric Western diet (WD) high in fat, sucrose and ch...
Article
Maternal diabetes interferes with fetal lung development and postnatal treatments may further disturb pulmonary growth. Therefore, we investigated the effect of postnatal oxygen exposure on alveolar development in neonatal rat lungs pre-exposed to intrauterine hyperglycemia. Diabetes was induced in Sprague-Dawley rats with streptozotocin injection...
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Abstract The intake of polyunsaturated fatty acids (PUFAs) is generally linked with a reduced cardiovascular disease (CVD) risk, but an elevated n6PUFA intake, without simultaneous n3PUFA supply, may elevate the risk. PUFAs are suspected as being easily oxidized and have a potential role in lipoprotein oxidation and inflammation. Saturated fatty ac...
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Oxidized LDL lipids (ox-LDL) are associated with lifestyle diseases such as cardiovascular diseases, metabolic syndrome and type 2 diabetes. The present study investigated how postpartum weight retention effects on ox-LDL and serum lipids. The study is a nested comparative research of a cluster-randomized controlled trial, NELLI (lifestyle and coun...
Article
Scavenging and reverse transport of atherogenic oxidized lipids by high-density lipoprotein (HDL) was recently suggested to contribute to atheroprotection. We investigated the associations of oxidized HDL lipids (oxHDLlipids) with known risk factors for atherosclerosis. Population-based cross-sectional study. A total of 1395 Finnish adults aged 24...
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Melanocyte-stimulating hormones, α-, β- and γ-MSH, regulate important physiological functions including energy homeostasis, inflammation and sodium metabolism. Previous studies have shown that α-MSH increases sodium excretion and promotes vascular function in rodents, but it is unexplored whether these characteristics of α-MSH could translate into...
Data
Analysis of NDP-α-MSH-evoked weight reduction by quantitative NMR scanning. Change in body weight (A), total body water (B), fat mass (C) and lean mass (D) after NDP-α-MSH administration. Body composition was analyzed by quantitative NMR scanning before and 2 hours after an i.p. injection of NDP-α-MSH (0.3 mg/kg). * P < 0.05 and ** P < 0.01 versus...
Data
Oxidative stress markers in the heart and kidney. Levels of 8-isoprostanes and conjugated dienes (CD) in the heart (A, C) and kidney (B, D). Number of mice analyzed is given in Table 1. # P < 0.05 versus control mice. (TIF)
Data
ROS formation in the aorta. (A) In situ dihydroethidium (DHE) staining of aortae from control and DOCA-salt mice. Red fluorescence indicates the presence of superoxide anions. Elastin fibers are seen as green due to autofluorescence. All sections are shown with the lumen at the right. Scale bars 100 μm. (B) Analysis of DHE intensity relative to sal...
Article
Purpose: We hypothesized that lower androgen status together with poor physical fitness associates with atherogenic lipid profile and oxidative stress. Methods: Volunteered young men (N = 846, mean age 25.1 ± 4.6 years) were categorized into unfit, average fit, and fit groups according to tertiles of maximal oxygen uptake, series of muscle endur...
Article
Background: Metabolic syndrome (MetS) is associated with increased oxidized LDL (ox-LDL), systemic inflammation, and poor cardiorespiratory fitness. We examined affiliations of these factors and the effect of muscular fitness on MetS in young healthy men. Methods: Physical fitness, ox-LDL, tumor necrosis factor α (TNFα), interleukin-6 (IL-6) and...
Article
Background: Oxidized low-density lipoprotein may be a key factor in the development of atherosclerosis. We performed a genome-wide association study on oxidized low-density lipoprotein and tested the impact of associated single-nucleotide polymorphisms (SNPs) on the risk factors of atherosclerosis and cardiovascular events. Methods and results:...
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Background and objective: the data concerning the predictive role of oxidised LDL (ox-LDL) in all-cause mortality are scarce. We investigated whether circulating ox-LDL would stand out as a risk factor of total mortality in the elderly. Study subjects, design and methods: a total of 1,260 elderly inhabitants (533 men, 727 women) aged 64 years or m...
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We studied effects of probiotics and training volume on oxidized LDL lipids (ox-LDL), serum antioxidant potential (s-TRAP) and serum antioxidants (s-α-tocopherol, s-γ-tocopherol, s-retinol, s-β-carotene and s-ubiquinone-10) in marathon runners during 3-months training period, 6-days preparation period and marathon run. Runners (n=127) were recruite...
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Objective: To test whether serum apolipoprotein B (apoB) and low-density lipoprotein (LDL) particle characteristics (oxidation and mean particle size) predict the incidence of metabolic syndrome (MetS). Methods: The 6-year follow-up study included 1429 adults (baseline mean age 31.5). Lipids, apoB, and apoA1 were measured at baseline in 2001. LD...
Article
Oxidized LDL (ox-LDL) is associated with lifestyle diseases such as cardiovascular diseases, metabolic syndrome, and type 2 diabetes. The present study investigated the association between ox-LDL and overweight/obesity and how cardiorespiratory or muscle fitness affects this association. Healthy young (mean age = 25.1 yr, range = 18-48 yr) men (n =...
Article
The present study investigated the composition and the antioxidative activities of oils from the seeds and the soft parts of a range of northern berries extracted by supercritical CO2. The seed oils of the species of Rubus, Vaccinium, Empetrum, Fragaria and Hippophaë were rich in linoleic (18:2n-6, 34–55% of total fatty acids) and α-linolenic (18:3...
Article
Good physical fitness is associated with favorable serum lipids. Oxidized low-density lipoprotein (ox-LDL) could be even more atherogenic than serum lipids. We studied the association of ox-LDL and serum lipids with physical fitness. Healthy young (mean age 25 years) men (n=846) underwent maximal oxygen uptake (VO(2max) ) and muscle fitness index (...
Article
Ectopic fat in muscle and liver is linked to obesity and type 2 diabetes. Recently, pancreatic lipid accumulation has also been associated with β-cell dysfunction and reduced insulin production, leading to the development of type 2 diabetes. Physical exercise training has been shown to attenuate β-cell dysfunction in patients, but little is known a...
Article
Aim. Intense physical training can induce an increase of oxidative stress. The aim of this study was to investigate the training effect of ice hockey and long distance running on oxidative stress by assessment of serum diene conjugation (DC) and antioxidant potential (TRAP). We also analyzed serum concentration of vitamins (α-tocopherol, γ-tocopher...
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Serum lipoproteins, the carriers of cholesterol and other lipophilic substances in blood, are known to contain variable amounts of lipid peroxides. We investigated the transport of food-derived and endogenously formed lipid peroxides by serum lipoproteins under physiological conditions. Five independent trials were conducted in which different grou...
Data
Full-text available
Background. Serum lipoproteins, the carriers of cholesterol and other lipophilic substances in blood, are known to contain variable amounts of lipid peroxides. We investigated the transport of food-derived and endogenously formed lipid peroxides by serum lipoproteins under physiological conditions. Methods. Five independent trials were conducted in...
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Full-text available
Cigarette smoke is strongly associated with NSCLC, but the carcinogenesis of NSCLC is poorly understood. To discover the role of oxidative stress and anti-oxidative defense in NSCLC, we measured NADPH oxidase (NOX) activity, myeloperoxidase activity, 8-OHdG, and glutathione content from lung specimens. These came from 32 patients: 22 NSCLC patients...
Article
Changes in generation of reactive oxygen species and antioxidant enzyme activities are associated with differentiation processes. The authors have studied the activity of superoxide dismutase (SOD) in sequentially cut stage-defined segments of rat seminiferous tubules. Great variation was observed in SOD activity along the seminiferous epithelial w...
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The interplay between smoking, oxidized low-density lipoprotein cholesterol (ox-LDL) and gonadal hormones has been scarcely investigated. To investigate associations in ox-LDL and gonadal hormones in smokers and non-smokers Participants (n=164) were obtained from a population cohort of Finnish men aged 40-70 years. The subjects answered a detailed...
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To investigate the effects of stanol ester margarine use in healthy subjects on arterial compliance, endothelial function and intima-media thickness. Case-control study comparing regular stanol ester margarine users to non-users. Occupational health service clinic. We recruited 50 cases and 50 controls (mean age 51+/-8, range 26-65 years). All subj...
Article
In order to study the effects of different athletic backgrounds on exercise-induced hormonal responses, serum testosterone, luteinizing hormone, follicle-stimulating hormone and cortisol concentrations were measured before and after intensive continuous and intermittent running in well-trained middle-distance runners (MID) and marathon runners (MAR...
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Oxidative stress has a role in the pathogenesis of gastroesophageal reflux disease (GERD). To investigate the redox balance in proximal esophagus before and 6 and 48 months after antireflux surgery. In 20 GERD patients and 9 controls oxidative stress by myeloperoxidase activity (MPO activity) and antioxidative capacity of esophageal mucosa by super...
Article
The most common marker of oxidative DNA damage is 8-hydroxydeoxyguanosine (8-OHdG), which is linked with several malignancies. In the present study we investigated whether DNA damage linked to oxidative stress (as 8-OHdG) is present in Barrett's mucosa with or without associated adenocarcinoma or high-grade dysplasia and in normal controls' squamou...
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We studied the association between weight maintenance, oxidized low-density lipoprotein (ox-LDL) and other lipoproteins in obese men. A 2-month weight reduction phase (WRP) with a very-low-energy diet was followed by a 6-month weight maintenance period and an unsupervised 2-year follow-up. Ninety men entered and 68 (76%) completed the study. Subjec...
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Flavonoids have recently been found in large amounts in knotwood and stemwood of several tree species. Six flavonoids, two flavonoid glucosides, and one cinnamic acid derivative were isolated from Jack pine and European aspen knotwood and structurally characterised using GC-MS, HR-MS, and NMR spectroscopic analyses. Isolated compounds were further...
Article
Sea buckthorn (Hippophaë rhamnoides L.) is a rich source of flavonols, especially isorhamnetin. Most prospective cohort studies have indicated some degree of inverse association between flavonoid intake and coronary heart disease. Animal and human studies suggest that sea buckthorn flavonoids may scavenge free radicals, lower blood viscosity, and e...
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The objective of this study was to identify risk markers for attenuated coronary flow velocity reserve (CFVR) that exist in healthy young men without evident atherosclerotic risk factors. Coronary blood flow velocity was measured with transthoracic Doppler echocardiography at baseline and during adenosine infusion in 37 healthy nonsmoking men [mean...
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The antioxidant properties of hydrophilic extracts of knotwood of several industrially important tree species were evaluated by lipid-peroxidation inhibition and peroxyl-trapping capacity tests. The results were compared with the antioxidant properties of hydrophilic extracts of bark, and pure lignans and flavonoids isolated from knotwood extracts....
Article
Oxidative stress to esophageal mucosa plays a key role in the pathogenesis of gastroesophageal reflux disease (GERD), Barrett's esophagus, and adenocarcinoma. We investigated whether successful antireflux surgery eliminates oxidative stress. Oxidative stress of esophageal mucosa was measured in 20 GERD patients, before antireflux surgery and 6 and...
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We studied the effects of a 2-day walk exercise (6 h+6 h) on the serum concentration of circulating moderately oxidized LDL (LDL baseline conjugated dienes), lipids (total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride), antioxidants (alpha-tocopherol, gamma-tocopherol, beta-carotene, and ubiquinol-10), and antioxidant potential in...
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The effects of two sunflower seed oil diets differing in oxidation levels (PV in oils 1 and 190 mequiv O2/kg) on lipoprotein TAG and total lipid oxidation were investigated in growing pigs. For 2 wk, two groups of 10 pigs were fed either of the diets, after which blood samples were collected. A method based on RP-HPLC and electrospray ionization-MS...
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The presence of TAG hydroperoxides in the epithelial cells of the small intestines in growing pigs was studied after they had consumed a diet rich in either nonoxidized or oxidized sunflower seed oil (PV in oils, 1 and 190 mequiv O2/kg, respectively). To obtain molecular-level information on the oxidized TAG structures, a new approach based on TLC...
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Oxidized lipoproteins have a recognized role in atherogenesis, but molecular-level research on oxidized lipids in lipoproteins and the effect of diet on these molecules have been limited. In the present study, the effects of three sunflower seed oil diets differing in oxidation levels (PV in oils 1, 84, and 223 mequiv O2/kg) on lipoprotein lipid ox...
Article
Diabetes has been associated with increased oxidative stress and impaired vascular function. Statins have been shown to reduce low-density lipoprotein (LDL) oxidizability and improve myocardial perfusion in hypercholesterolemic nondiabetic subjects. We studied whether pravastatin decreases LDL oxidation and improves myocardial perfusion in normocho...
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The oxidation of human LDL lipids and the structures of oxidized TAG molecules found in LDL were investigated. Pooled samples of 10 normolipidemic and 10 hyperlipidemic subjects were analyzed. For determination of the oxidation levels, the LDL baseline diene conjugation (LDL-BDC) method was used. A method based on HPLC and electrospray ionization-M...
Article
Statins are known to cause short-term reduction in serum lipid-soluble antioxidant concentrations, but their long-term effects are not known. We randomised 104 subjects with CHD and hypercholesterolaemia to receive either atorvastatin or simvastatin treatment for 52 weeks and measured the antioxidant potential of LDL and serum antioxidant vitamin c...
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Oxidized low density lipoprotein (LDL) plays a key role in processes leading to atherosclerosis. Recent studies show that LDL oxidation in vitro is effectively prevented by estrogen. Yet, the effect of hormonal therapy (HT) on in vivo LDL oxidation has remained open. We used a novel methodology for the measurement of oxidized LDL in vivo in order t...
Article
Obesity is associated with endothelial dysfunction that may contribute to the development of atherosclerosis. We studied whether weight reduction improves endothelial function in overweight individuals. Flow-mediated endothelium-dependent vasodilation of the brachial artery was measured in 67 adults (age: 46+/-7 years, body mass index: 35.2+/-5.4 k...
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Because dietary fat appears to be an effective vehicle for dispensing plant sterols into the diet, a special plant-sterol-containing ingredient has recently been developed. This ingredient is a plant sterol suspension in oil in which the sterols are in microcrystalline form. The objective of the present study was to analyse the cholesterol-lowering...