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- Sierra-Johnson, Justo
(author)
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Novel epidemiologic and mechanistic aspects of the metabolic syndrome
- 2009
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Doctoral thesis (other academic/artistic)abstract
- Introduction: The metabolic syndrome is a cluster of cardiometabolic risk factors that increase risk of developing cardiovascular disease. Its prevalence continues to rise worldwide and it is becoming a public health burden. The aim of my thesis was to help elucidate some of the epidemiologic and mechanistic aspects behind the metabolic syndrome. Material and Methods: For paper I the National Health and Nutrition Examination Survey (NHANES) III was used. For paper II the NHANES III Mortality study was used with follow-up mortality on NHANES III subjects. For paper III, the 60 year old Stockholm county cohort, the Swedish Diet and metabolic syndrome (KOMET) study and the NHANES 2005-06 cohorts were used. For paper IV, the 65 year old Stockholm County physical activity intervention study was used. Results: Paper I showed that the apolipoproteinB/apolipoproteinAI (apoB/apoAI) ratio is strongly associated with insulin resistance beyond the association explained by traditional risk factors, metabolic syndrome components, and inflammatory risk factors. Paper II showed that apolipoprotein measurements significantly predict coronary heart disease (CHD) death, independently of cardiovascular (CV) risk factors and that this predicting ability was better than any of the routine clinical lipid measurements. Paper III showed that gamma glutamyl transferase (GGT) is significantly associated with the metabolic syndrome in elderly asymptomatic subjects and that this association seems to be mediated, at least in part by C-reactive protein (CRP). Paper IV showed that change in adipose tissue gene expression is associated with changes in metabolic syndrome parameters. Furthermore, lifestyle modification can influence changes in adipose tissue gene expression, which may in turn modulate metabolic syndrome parameters. Conclusions: ApoB/apoAI ratio is a marker of insulin resistance. Apolipoprotein B should be included in guidelines assessing cardiometabolic risk. GGT relationship to the metabolic syndrome seems to be mediated, at least in part, by changes in CRP. Changes in parameters of the metabolic syndrome seem to be mediated, at least in part, by changes in adipose tissue gene expression after increased physical activity.
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| 3. |
- Sjögren, Per, et al.
(author)
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Functional changes in adipose tissue in a randomised controlled trial of physical activity
- 2012
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In: Lipids in Health and Disease. - 1476-511X. ; 11, s. 80-
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Journal article (peer-reviewed)abstract
- Background: A sedentary lifestyle predisposes to cardiometabolic diseases. Lifestyle changes such as increased physical activity improve a range of cardiometabolic risk factors. The objective of this study was to examine whether functional changes in adipose tissue were related to these improvements. Methods: Seventy-three sedentary, overweight (mean BMI 29.9 +/- 3.2 kg/m(2)) and abdominally obese, but otherwise healthy men and women (67.6 +/- 0.5 years) from a randomised controlled trial of physical activity on prescription over a 6-month period were included (control n = 43, intervention n = 30). Detailed examinations were carried out at baseline and at follow-up, including fasting blood samples, a comprehensive questionnaire and subcutaneous adipose tissue biopsies for fatty acid composition analysis (n = 73) and quantification of mRNA expression levels of 13 candidate genes (n = 51), including adiponectin, leptin and inflammatory cytokines. Results: At follow-up, the intervention group had a greater increase in exercise time (+ 137 min/week) and a greater decrease in body fat mass (-1.5 kg) compared to the control subjects (changes of 0 min/week and -0.5 kg respectively). Circulating concentrations of adiponectin were unchanged, but those of leptin decreased significantly more in the intervention group (-1.8 vs - 1.1 ng/mL for intervention vs control, P < 0.05). The w6-polyunsaturated fatty acid content, in particular linoleic acid (18:2w6), of adipose tissue increased significantly more in the intervention group, but the magnitude of the change was small (+ 0.17 vs + 0.02 percentage points for intervention vs control, P < 0.05). Surprisingly leptin mRNA levels in adipose tissue increased in the intervention group (+ 107% intervention vs -20% control, P < 0.05), but changes in expression of the remaining genes did not differ between the groups. Conclusions: After a 6-month period of increased physical activity in overweight elderly individuals, circulating leptin concentrations decreased despite increased levels of leptin mRNA in adipose tissue. Otherwise, only minor changes occurred in adipose tissue, although several improvements in metabolic parameters accompanied the modest increase in physical activity.
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