Metabolic syndrome and early death: getting to the heart of the problem.
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Humans↗
Biomedical subjects
Tommy Olsson
Publications and source records attributed to Tommy Olsson.
Increased cortisol responsivity to adrenocorticotropic hormone and low plasma levels of interleukin-1 receptor antagonist in women with functional hypothalamic amenorrhea.
OBJECTIVE: To assess the hypothalamic-pituitary-adrenal (HPA) axis at all levels, to determine the origin of the previously reported hypercortisolism in patients with functional hypothalamic amenorrhea. A secondary aim was to evaluate factors outside the central nervous system which are known to affect the HPA axis, i.e., circulating levels of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and fat mass-adjusted leptin levels, in patients with functional hypothalamic amenorrhea and healthy controls. DESIGN: Cross-sectional study. SETTING: Umeå University Hospital, Umeå, Sweden. PATIENTS: Fifteen subjects with hypothalamic amenorrhea, and 14 age- and weight-matched controls. INTERVENTIONS: None. MAIN OUTCOME MEASURES: We collected blood samples four times during a 24-hour interval for analysis of cortisol, leptin, IL-1Ra, and IL-6 levels. We performed a low-dose oral dexamethasone test and a low-dose ACTH test. We measured body-fat percentage using a dual-energy X-ray absorptiometer. RESULTS: Patients with hypothalamic amenorrhea had increased diurnal cortisol levels (P<.001). The cortisol response to intravenous low-dose ACTH was increased in functional hypothalamic amenorrhea patients compared to control subjects (P<.01), but they had similar rates of dexamethasone suppression. Patients with hypothalamic amenorrhea also had decreased diurnal leptin (P<.05), and decreased diurnal IL-1Ra levels (P<.05), compared to controls. Body-fat percentage was the main predictor of leptin levels. CONCLUSION: The present study suggests novel links for the development of functional hypothalamic amenorrhea, including increased adrenal responsiveness and impairments in proinflammatory cytokine pathways.
Adrenocorticotropic Hormone↗
Sustained benefits from previous physical activity on bone mineral density in males.
CONTEXT: The effect of physical activity on bone mineral density (BMD) is not well investigated longitudinally after puberty in men. OBJECTIVE: Our objective was to evaluate the effect of exercise and reduced exercise on BMD after puberty in men. DESIGN: We conducted a longitudinal study. PARTICIPANTS: Sixty-three healthy young athletes and 27 male controls, both with a mean age of 17 yr at baseline, participated. Also, 136 of the participants' parents were investigated to evaluate heritable influences. MAIN OUTCOME MEASURES: Total body, total hip, femoral neck, and humerus BMD (grams per square centimeter) were measured at baseline and after mean periods of 27, 68, and 94 months in the young cohort. RESULTS: BMDs of control parents and athlete parents were equal, suggesting absence of selection bias. The 23 athletes that remained active throughout the study increased BMD at all sites when compared with controls (mean difference, 0.04-0.12 g/cm(2); P < 0.05) during the study period. After an average of 3 yr, 27 athletes ended their active careers. Although this group initially lost BMD at the hip compared with active athletes, the former athletes still had higher BMD than controls at the femoral neck (0.12 g/cm(2); P = 0.007), total hip (0.11 g/cm(2); P = 0.02), and humerus (0.10 g/cm(2); P = 0.02) at the final follow-up. CONCLUSIONS: High sensitivity to physical loading persists after puberty in men. Reduced physical activity is associated with BMD loss in the first 3 yr in weight-bearing bone. Sustained benefits in BMD are preserved 5 yr after intensive training ends.
Adolescent↗
The importance of atmospheric deposition, charge and atomic mass to the dynamics of minor and rare elements in developing, ageing, and wilted leaves of beech (Fagus sylvatica L.).
The amounts of sixty elements in developing, maturing, senescent and wilting leaves, and in the wintering dead leaves attached to the branches, are reported for a beech (Fagus sylvatica) forest on mor Podzol in south Sweden, a site with no local sources of pollution or geological anomalies. The amounts (contents per leaf) of K (potassium), Rb (rubidium), Cs (caesium), Cu (copper) and P (phosphorus) were highest in young leaves, decreasing throughout the growing season and usually in the subsequent winter. The entirely opposite pattern with a continuous, mostly even increase of the amounts was measured with Be (beryllium), Ba (barium), Hg (mercury), Al (aluminium), Tl (thallium), Pb (lead), Bi (bismuth), V (vanadium), W (tungsten), As (arsenic), Sb (antimony), and Se (selenium). Amounts of rare-earth elements and some transition metals, such as Co (cobalt), Ti (titanium), and the actinides Th (thorium) and U (uranium) were more stable during the growing season, after an initial increase in early summer, but increased greatly in the winter. This winter increase in dead attached leaves has to be accounted for by uptake from long-distance transported constituents in dry and wet deposition. It was similar to deposition rate estimates using moss carpets from the same locality. A passive uptake was positively related to ionic charge and atomic mass. However, the amounts of several, mainly non-essential elements, such as Ni (nickel), Sc (scandium), Zr (zirconium), Cr (chromium), Ag (silver), and Cd (cadmium) were not much lower in the young or maturing leaves than in the wintered dead leaves of this deciduous (hardwood) forest and a proportion apparently originated from internal translocation in the trees. Seasonal fluxes or cycling of many of the scarce or rare elements reported here have never been studied before in forest ecosystems.
Air Pollutants↗
Neuroactive steroid effects on cognitive functions with a focus on the serotonin and GABA systems.
This article will review neuroactive steroid effects on serotonin and GABA systems, along with the subsequent effects on cognitive functions. Neurosteroids (such as estrogen, progesterone, and allopregnanolone) are synthesized in the central and peripheral nervous system, in addition to other tissues. They are involved in the regulation of mood and memory, in premenstrual syndrome, and mood changes related to hormone replacement therapy, as well as postnatal and major depression, anxiety disorders, and Alzheimer's disease. Estrogen and progesterone have their respective hormone receptors, whereas allopregnanolone acts via the GABA(A) receptor. The action of estrogen and progesterone can be direct genomic, indirect genomic, or non-genomic, also influencing several neurotransmitter systems, such as the serotonin and GABA systems. Estrogen alone, or in combination with antidepressant drugs affecting the serotonin system, has been related to improved mood and well being. In contrast, progesterone can have negative effects on mood and memory. Estrogen alone, or in combination with progesterone, affects the brain serotonin system differently in different parts of the brain, which can at least partly explain the opposite effects on mood of those hormones. Many of the progesterone effects in the brain are mediated by its metabolite allopregnanolone. Allopregnanolone, by changing GABA(A) receptor expression or sensitivity, is involved in premenstrual mood changes; and it also induces cognitive deficits, such as spatial-learning impairment. We have shown that the 3beta-hydroxypregnane steroid UC1011 can inhibit allopregnanolone-induced learning impairment and chloride uptake potentiation in vitro and in vivo. It would be important to find a substance that antagonizes allopregnanolone-induced adverse effects.
Animals↗
Gene expression profiling of the rat hippocampus one month after focal cerebral ischemia followed by enriched environment.
Functional recovery after experimental stroke in rats is enhanced by environmental enrichment by stimulating plastic changes in brain regions outside the lesion, but the molecular mechanisms are not known. We investigated the effect of environmental enrichment after focal cerebral ischemia on cognitive recovery and hippocampal gene expression using microarray analysis. Rats placed in enriched environment (EE) for 1 month after middle cerebral artery occlusion (MCAo) showed significantly improved spatial memory in the Morris water maze compared to rats housed alone after MCAo. Microarray analysis suggested several EE-induced differences in neuronal plasticity-related genes, but these changes could not be confirmed by quantitative real-time PCR. This study highlights some of the potential problems associated with gene expression profiling of brain tissues. Further studies at earlier time points and in additional subregions of the brain are of interest in the search for molecular mechanisms behind EE-induced neuronal plasticity after ischemic stroke.
Animals↗
Cognitive dysfunction, hippocampal atrophy and glucocorticoid feedback in Alzheimer's disease.
BACKGROUND: The hippocampal formation is damaged early in Alzheimer's disease (AD). An association between temporal lobe volume and cognitive function has been shown in several studies. Increased limbic-hypothalamic-pituitary-adrenal (LHPA) axis function has been suggested to be related to hippocampal atrophy and cognitive impairment. Our hypothesis was that there is a clear link between hippocampal volume -- notably of the CA1 region -- memory (episodic and visuospatial) and decreased feedback sensitivity in the LHPA axis in AD. METHODS: Sixteen medication-free outpatients with mild to moderate AD were included. Hippocampal volume was measured with magnetic resonance imaging. Dexamethasone suppression tests were performed using .5 mg and .25 mg dexamethasone. Three different components in the neuropsychological battery -- Rey 15 item memory test, Alzheimer's Disease Assessment Scale (ADAS) word recall and spatial span from Wechsler Adult Intelligence Scale - Revised neuropsychological instrument (WAIS-R NI) -- were found to represent episodic and visuospatial memory. RESULTS: Low hippocampal CA1 volume and high post-dexamethasone cortisol levels in combination were significantly associated with Rey 15 item memory and spatial span test outcomes. No association was found between LHPA feedback and hippocampal volume. CONCLUSIONS: Low hippocampal volume and a disturbed negative feedback in the LHPA axis link to specific cognitive impairments in Alzheimer's disease.
Aged↗
A unique role of monocyte chemoattractant protein 1 among chemokines in adipose tissue of obese subjects.
CONTEXT: Low-grade inflammation in adipose tissue may contribute to insulin resistance in obesity. However, the roles of individual inflammatory mediators in adipose tissue are poorly understood. OBJECTIVES: The objective of this study was to determine which inflammation markers are most overexpressed at the gene level in adipose tissue in human obesity and how this relates to corresponding protein secretion. DESIGN: We examined gene expression profiles in 17 lean and 20 obese subjects. The secretory pattern of relevant corresponding proteins was examined in human s.c. adipose tissue or isolated fat cells in vitro and in vivo in several obese or lean cohorts. RESULTS: In ranking gene expression, defined pathways associated with obesity and immune and defense responses scored high. Among seven markedly overexpressed chemokines, only monocyte chemoattractant protein 1 (MCP1) was released from adipose tissue and isolated fat cells in vitro. In obesity, the secretion and expression of MCP1 in adipose tissue pieces were more than 6- and 2-fold increased, respectively, but there was no change in circulating MCP1 levels. There was no net release of MCP1, but there was a net release of leptin, in vivo from adipose tissue into the circulation. CONCLUSIONS: Obesity is associated with the increased expression of several chemokine genes in adipose tissue. However, only MCP1 is secreted into the extracellular space, where it primarily acts as a local factor, because little or no spillover into the circulation occurs. MCP1 influences the function of adipocytes, is a recruitment factor for macrophages, and may be a crucial link among chemokines between adipose tissue inflammation and insulin resistance.
Adipose Tissue↗
Diurnal effects of enriched environment on immediate early gene expression in the rat brain.
Rodents housed in an enriched environment (EE) show increased neuronal plasticity with enhanced long-term potentiation and memory performance. We report an EE-induced increase in NGFI-A and Krox-20 mRNA expression exclusively during the dark period of the day. In addition, EE-housed rats showed considerable diurnal variation in NGFI-A, Krox-20, and NGFI-B mRNA expression which was absent in single-housed rats. Thus, EE-induced molecular changes are more evident during the dark phase when the rats have higher motor and exploratory activity. This is important to take into account in future studies of molecular mediators of experience-dependent neuronal plasticity.
Analysis of Variance↗
Impaired cognitive performance in patients with chronic burnout syndrome.
Chronic burnout refers to a syndrome caused by chronic stress. Clinical observations indicate that chronic burnout is associated with impaired cognitive functioning. However, there have been no systematic studies of the cognitive performance in chronic burnout patients. We have evaluated general cognitive ability, memory, and attention in 67 female patients treated for chronic burnout. The patients and 15 healthy control subjects were tested with standardized tests of verbal and nonverbal cognitive ability (WAIS), verbal (Claeson-Dahl) and nonverbal (Rey complex figures) memory, and visual and auditory attention (IVA). Significant reductions in nonverbal memory and auditory and visual attention were found for the patient group. These results indicate that patients with chronic burnout have specific cognitive impairments, which should be emphasized in the evaluation of symptoms and treatment regimes in this disorder.
Adult↗
Dysregulation of the autonomic nervous system can be a link between visceral adiposity and insulin resistance.
OBJECTIVE: To evaluate the interplay among abdominal adipose tissue distribution, the cortisol axis, the autonomic nervous system, and insulin resistance. RESEARCH METHODS AND PROCEDURES: Two age-, sex-, and BMI-matched groups were studied. Fifteen subjects were first-degree relatives of patients with type 2 diabetes (R), and 15 had no family history of diabetes (controls, C). A hyperinsulinemic euglycemic clamp, cortisol measurements, and analysis of heart rate variability (HRV) were performed. Computed tomography was performed in a subgroup (n = 9 + 9) to determine abdominal adipose tissue distribution. RESULTS: R tended to be less insulin-sensitive than C (M value 9.2 +/- 1.0 vs 10.3 +/- 0.7 mg/kg per minute, not significant). Stimulation with tetracosactin or corticotropin releasing hormone yielded lower peak serum cortisol levels in R (p = 0.03 and p = 0.06, respectively). The amount of visceral abdominal fat (VAT) tended to be greater in R. In all subjects, VAT was negatively correlated to insulin sensitivity (r = -0.93, p < 0.001). There was a positive association between VAT and resting heart rate (r = 0.70, p = 0.003) and sympathetic/parasympathetic ratio in HRV assessment after tilt (r = 0.53, p = 0.03). Subcutaneous abdominal tissue was not associated with insulin sensitivity or any of the hormonal or HRV assessments. DISCUSSION: Subjects genetically predisposed for type 2 diabetes had a tendency toward a larger amount of VAT and to lower insulin sensitivity compared with control subjects. The amount of visceral fat was strongly associated with insulin resistance and signs of a high ratio of sympathetic vs. parasympathetic reactivity. A large amount of visceral fat may act in concert with sympathetic/parasympathetic imbalance to promote the development of insulin resistance, and this may be partly independent of genetic background.
Adipose Tissue↗
Rare earth elements in forest-floor herbs as related to soil conditions and mineral nutrition.
Mixtures of rare earth elements (REEs) in fertilizers are widely used in Chinese agriculture to improve crop nutrition. REE concentrations in wild-growing plants, especially herbs, are little known. This study describes differences in the concentrations and proportions of REEs in eight forest-floor herbaceous plants and relates these differences to soil and mineral nutrient conditions. REEs studied were yttrium (Y), lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), samarium (Sm), europium (Eu), gadolinium (Gd), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb), and lutetium (Lu). Leaf concentrations of sum REEs differed more than one order of magnitude between species, being highest in Anemone nemorosa (10.1 nmol/g dry mass) and lowest in Convallaria majalis (0.66 nmol/g) from the same site. Leaf concentrations of all REEs correlated positively (p < 0.001), as did sum REE with calcium (Ca) and strontium (Sr) concentrations (p < 0.001). A negative relationship (r = -0.83, (p < 0.001) was measured between phosphorus (P) concentrations and sum REE concentrations in leaves. However, the proportions of the single REEs in the REE sum differed among species. In A. nemorosa, 57% of the molar REE sum was taken by Y + La, and only 21% by Ce. The other extreme was Maianthemum bifolium, with 37% La + Y and 41% Ce. These two species had 2.7-3.0% of the REE sum as heavier lanthanides, compared to 4.1-5.2% in the six other species. No clear relationship between soil properties or REE contents and leaf REE concentrations was detected. For La, however, an overrepresentation in leaves prevailed throughout all species compared to soils, whereas particularly Nd, Sm, and Tb had a lower proportion in the leaves of all species than in their soils. Possible uptake mechanisms of REEs in plants are discussed.
Agriculture↗
Bone gained from physical activity and lost through detraining: a longitudinal study in young males.
The aim of this study was to investigate the effect of training and detraining on bone mineral density of both weight-bearing and non-weight-bearing bone in a cohort of young males who participated in ice hockey training. Forty-three healthy adolescent ice hockey players (16.7+/-0.6 years) training for a mean of 9.7+/-2.4 h/week and 25 control subjects (16.8+/-0.3 years) training for 2.1+/-2.7 h/week, were included in this longitudinal study. Bone mineral density (BMD, g/cm2) of the arms, the dominant and non-dominant humerus, dominant and non-dominant femur, and the right femoral neck, total hip, and bone area of the femur, humerus and hip were measured at baseline and again after 30 and 70 months using dual-energy X-ray absorptiometry. From baseline to the first follow-up, athletes gained significantly more BMD in the femoral neck (0.07 versus 0.03 g/cm2) and arms (0.09 versus 0.06 g/cm2) compared with the controls (P = 0.04 for both). Between the first and the second follow-up, 21 ice hockey players stopped their active sports career. These men lost significantly more BMD at the femoral neck (-0.02 versus -0.10 g/cm2, P < 0.001), total hip (-0.05 versus -0.09, P = 0.04), dominant (0.02 versus -0.03 g/cm2, P = 0.009) and non-dominant humerus (0.03 versus -0.01 g/cm2, P = 0.03) than the still active ice hockey players (n = 22). At the second follow-up examination, at 22 years of age, the former ice hockey players still had significantly higher BMD at the non-dominant humerus than the controls (P < 0.01). During the total study period, the still active athletes (n = 22) gained significantly more BMD compared with the controls at the femoral neck (0.09 g/cm2; P = 0.008), total hip (0.05 g/cm2, P = 0.04) and arms (0.07 g/cm2; P = 0.01). No differences were seen in bone areas when comparing the different groups. In conclusion, training associated with ice hockey is related to continuous accumulation of BMD after puberty in males. Reduced activity is followed by BMD loss within 3 years of cessation of sports career at predominantly weight-bearing sites. The effects are confined to bone density and not bone size.
Absorptiometry, Photon↗
Bone loss and fracture risk after reduced physical activity.
UNLABELLED: Former male young athletes partially lost benefits in BMD (g/cm2) with cessation of exercise, but, despite this, had a higher BMD 4 years after cessation of career than a control group. A higher BMD might contribute to the lower incidence of fragility fractures found in former older athletes > or =60 years of age compared with a control group. INTRODUCTION: Physical activity increases peak bone mass and may prevent osteoporosis if a residual high BMD is retained into old age. MATERIALS AND METHODS: BMD was measured by DXA in 97 male young athletes 21.0 +/- 4.5 years of age (SD) and 48 controls 22.4 +/- 6.3 years of age, with measurements repeated 5 years later, when 55 of the athletes had retired from sports. In a second, older cohort, fracture incidence was recorded in 400 former older athletes and 800 controls > or =60 years of age. RESULTS: At baseline, the young athletes had higher BMD than controls in total body (mean difference, 0.08 g/cm2), spine (mean difference, 0.10 g/cm2), femoral neck (mean difference, 0.13 g/cm2), and arms (mean difference, 0.05 g/cm2; all p < 0.001). During the follow-up period, the young athletes who retired lost more BMD than the still active athletes at the femoral neck (mean difference, 0.07 g/cm2; p = 0.001) and gained less BMD at the total body (mean difference, 0.03 g/cm2; p = 0.004). Nevertheless, BMD was still higher in the retired young athletes (mean difference, 0.06-0.08 g/cm2) than in the controls in the total body, femoral neck, and arms (all p < 0.05). In the older cohort, there were fewer former athletes > or =60 of age than controls with fragility fractures (2.0% versus 4.2%; p < 0.05) and distal radius fractures (0.75% versus 2.5%; p < 0.05). CONCLUSIONS: Although exercise-induced BMD benefits are reduced after retirement from sports, former male older athletes have fewer fractures than matched controls.
Absorptiometry, Photon↗
Obesity and colon cancer: does leptin provide a link?
Obesity, a risk factor for colorectal cancer, is associated with elevated serum levels of leptin, the adipocyte-derived hormone, and insulin. Experimental and epidemiologic studies have indicated a role for insulin in the pathogenesis of colon cancer, and recent experimental studies have suggested a similar role for leptin. In a case-control study nested in the Janus Biobank, Norway, we measured serum levels of leptin and C-peptide (a marker of pancreatic insulin secretion) in cryopreserved prediagnostic sera from men (median age, 45 years) who were diagnosed with cancer of the colon (n = 235) or rectum (n = 143) after blood collection (median time, 17 years), and among 378 controls matched for age and date of blood collection. Conditional logistic regression analyses showed an approximately 3-fold increase in colon cancer risk with increasing concentrations of leptin up to an odds ratio (OR) of 2.72 (95% CI = 1.44-5.12) for top vs. bottom quartile (p(trend) = 0.008). The corresponding OR for C-peptide was 1.81 (95% CI = 0.67-4.86; p(trend) = 0.19). The risk estimates remained unchanged after mutual adjustment. No association of hormone levels with rectal cancer risk was found. Reproducibility of hormone measurements assessed by intraclass coefficients (ICCs) for paired samples taken 1 year apart was high for leptin (ICC = 0.82) but lower for C-peptide (ICC = 0.30). Our results suggest that leptin is a risk factor for colon cancer, and that leptin may provide a link between obesity and colon cancer. Leptin may be directly involved in colon tumorigenesis or it may serve as a sensitive and robust marker of an obesity-induced adverse endocrine environment. Only weak support for an association of insulin with colon cancer was found.
Adult↗
Plasma leptin and breast cancer risk: a prospective study in northern Sweden.
INTRODUCTION: Obesity is associated with risk of breast cancer after menopause. Circulating levels of leptin are high in obesity and leptin stimulates growth of breast cancer cells. MATERIAL AND METHODS: In a case-control study nested within the Northern Sweden Health and Disease Cohort, we measured leptin levels in prediagnostic plasma from 149 postmenopausal women who were diagnosed with breast cancer at a mean time 1.7 years (SD 2.0) after recruitment and among 258 control subjects. RESULTS: No significant association between plasma levels of leptin and breast cancer risk was observed. Odds ratios (ORs) of breast cancer with increasing levels of leptin were 1.00 [referent], 1.01 [95% CI = 0.58-1.84], 0.65 [0.36-1.18], and 0.94 [0.53-1.67], and (p(for trend) = 0.54). Adjustment for smoking, body mass index, and plasma insulin did not affect risk estimates. DISCUSSION: These data do not support the hypothesis that plasma leptin is a risk factor for breast cancer.
Aged↗
Serum insulin-like growth factor-1 is an independent predictor of prognosis in patients with renal cell carcinoma.
Obesity is associated with an increased risk of certain cancers, including renal cell carcinoma. A possible mediator of this risk is insulin-like growth factor-1 (IGF-1). The authors evaluated the prognostic information of IGF-1, IGFBP-3, leptin, and prealbumin in sera sampled at diagnosis from 256 consecutive patients with renal cell carcinoma. Insulin-like growth factor-1 and leptin were positively correlated to body mass index (BMI). Insulin-like growth factor-1 and IGFBP-3 did not correlate to tumour stage or grade. Leptin and prealbumin were both inversely related to tumour stage and grade. When survival was analysed in patients with levels above a median of IGF-1, leptin, and prealbumin, prognosis was more favourable, compared with those with lower levels (p=0.017; p=0.024, and p<0.0001, respectively). In a multivariate analysis, tumour stage and serum IGF-1 levels were independent prognostic factors. The results indicate that serum IGF-1 at diagnosis is related to prognosis in renal cell carcinoma.
Adult↗
Environmental enrichment reverses learning impairment in the Morris water maze after focal cerebral ischemia in rats.
Cognitive impairment is common after ischemic stroke. In rodent stroke models using occlusion of the middle cerebral artery (MCA) this is reflected by impaired spatial memory associated with the size of the ischemic lesion. Housing in an enriched environment enhances brain plasticity and improves recovery of sensorimotor functions after experimental stroke in rats. In this study we report that postischemic housing in an enriched environment also attenuates the long-term spatial memory impairment after MCA occlusion and extinguishes the association between spatial memory and infarct volume. An enriched environment did not significantly alter the expression of selected neuronal plasticity-associated genes 1 month after MCA occlusion, indicating that most of the adaptive changes induced by an enriched environment have already occurred at this time point. We conclude that the attenuated memory impairment induced by environmental enrichment after MCA occlusion provides a useful model for further studies on the neurobiological mechanisms of recovery of cognitive functions after ischemic stroke.
Animals↗