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- Kolak, Maria, et al.
(författare)
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Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity
- 2007
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 56:8, s. 1960-1968
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We sought to determine whether adipose tissue is inflamed in individuals with increased liver fat (LFAT) independently of obesity.RESEARCH DESIGN AND METHODS: A total of 20 nondiabetic, healthy, obese women were divided into normal and high LFAT groups based on their median LFAT level (2.3 +/- 0.3 vs. 14.4 +/- 2.9%). Surgical subcutaneous adipose tissue biopsies were studied using quantitative PCR, immunohistochemistry, and a lipidomics approach to search for putative mediators of insulin resistance and inflammation. The groups were matched for age and BMI. The high LFAT group had increased insulin (P = 0.0025) and lower HDL cholesterol (P = 0.02) concentrations.RESULTS: Expression levels of the macrophage marker CD68, the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein-1alpha, and plasminogen activator inhibitor-1 were significantly increased, and those of peroxisome proliferator-activated receptor-gamma and adiponectin decreased in the high LFAT group. CD68 expression correlated with the number of macrophages and crown-like structures (multiple macrophages fused around dead adipocytes). Concentrations of 154 lipid species in adipose tissue revealed several differences between the groups, with the most striking being increased concentrations of triacylglycerols, particularly long chain, and ceramides, specifically Cer(d18:1/24:1) (P = 0.01), in the high LFAT group. Expression of sphingomyelinases SMPD1 and SMPD3 were also significantly increased in the high compared with normal LFAT group.CONCLUSIONS: Adipose tissue is infiltrated with macrophages, and its content of long-chain triacylglycerols and ceramides is increased in subjects with increased LFAT compared with equally obese subjects with normal LFAT content. Ceramides or their metabolites could contribute to adverse effects of long-chain fatty acids on insulin resistance and inflammation.
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| 2. |
- Kolak, Maria
(författare)
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Adipose tissue inflammation, hepatic fat accumulation and insulin resistance
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Insulin resistance is the central feature of a variety of metabolic disorders, such as type 2 diabetes and the metabolic syndrome. The incidence of these disorders, often together with obesity, is currently increasing throughout the world. Insulin resistance occurs together with obesity, but also when adipose tissue is absent, indicating an important role of normal adipose tissue function for the maintenance of insulin sensitivity. Also, an accumulation of fat in the liver is observed together with both the excess and the absence of adipose tissue and insulin resistance. The interplay between the metabolic disturbances in adipose tissue and accumulation of fat in the liver which may underlie the development of insulin resistance is not well understood. Therefore, the aim of this thesis is to improve our knowledge of the molecular pathways underlying metabolic disturbances in adipose tissue and hepatic fat accumulation as well as the interplay between them in order to better understand the development of insulin resistance and related disorders in man. Twenty type 2 diabetes patients were treated with either rosiglitazone (an insulin sensitizer, an agonist of the transcription factor PPAR , which is predominantly expressed in adipose tissue) or metformin (an insulin sensitizer believed to act mainly in the liver). Rosiglitazone decreased liver fat content in these patients, while metformin did not. Biopsies from subcutaneous adipose tissue were taken before and after 16 weeks of treatment. Expression of 50 genes previously shown to be altered by TZDs in experimental models was measured. We found that rosiglitazone, but not metformin treatment, increased expression of genes involved in fatty acid synthesis and storage and in glucose uptake and decreased some macrophage and inflammation markers. This suggests that together with an improvement in insulin sensitivity and a decrease in liver fat content, rosiglitazone increases lipid storage and decreases inflammation within subcutaneous adipose tissue. In order to investigate changes in the liver when it becomes fatty, we analyzed gene expression in liver biopsies from 24 subjects with histologically determined liver fat content ranging from normal (n=8) to non-alcoholic hepatic steatosis (n=16). We found that expression of genes involved in fatty acid storage and inflammation was grater in livers of subjects with high liver fat content, indicating an alteration of hepatic gene expression towards an adipogenic and inflammatory profile upon excess fat accumulation. Next, we investigated whether adipose tissue is inflamed in subjects with increased liver fat content independently of the degree of obesity. Twenty obese, but otherwise healthy women with a wide range of liver fat contents were recruited and divided in normal liver fat (n=10) and high liver fat (n=10) groups. Biopsies from subcutaneous adipose tissue were analyzed by quantitative PCR, immunohistochemistry and lipidomic analysis. Expression of inflammatory markers was higher in the adipose tissue of women with high liver fat. Immunohistochemical analysis revealed increased macrophage infiltration in adipose tissue of women with high liver fat. These macrophages were mostly found surrounding dead adipocytes. Lipidomic analysis showed higher concentrations of long-chain TGs and some sphingomyelins and ceramides in the adipose tissue of women with high liver fat. In order to investigate the increase in ceramides in the inflamed adipose tissue of women with high liver fat content, we characterized ceramide metabolism within adipose tissue. Gene expression analysis suggested that the increase in ceramide might be explained by an increase in sphingomyelin hydrolysis by sphingomyelinases, especially by SMPD3, rather than by de novo synthesis of ceramide. Sphingomyelinases were expressed by both adipocytes and macrophages, but strongest expression was found in and around blood vessels within adipose tissue. In summary, the work contained in this thesis demonstrates the importance of inflammation in adipose tissue and liver and the degree of hepatic fat accumulation, but not the degree of obesity per se, in the development of insulin resistance. Sphingomyelin-mediated ceramide production, which shares some features with the process of atherosclerosis, offers a link between the accumulation of fat in the liver and the development of inflammation in adipose tissue.
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| 3. |
- Kolak, Maria, et al.
(författare)
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Expression of ceramide-metabolising enzymes in subcutaneous and intra-abdominal human adipose tissue
- 2012
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Ingår i: Lipids in Health and Disease. - : BioMed Central (BMC). - 1476-511X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Inflammation and increased ceramide concentrations characterise adipose tissue of obese women with high liver fat content compared to equally obese women with normal liver fat content. The present study characterises enzymes involved in ceramide metabolism in subcutaneous and intra-abdominal adipose tissue.METHODS: Pathways leading to increased ceramide concentrations in inflamed versus non-inflamed adipose tissue were investigated by quantifying expression levels of key enzymes involved in ceramide metabolism. Sphingomyelinases (sphingomyelin phosphodiesterases SMPD1-3) were investigated further using immunohistochemistry to establish their location within adipose tissue, and their mRNA expression levels were determined in subcutaneous and intra-abdominal adipose tissue from both non-obese and obese subject.RESULTS: Gene expression levels of sphingomyelinases, enzymes that hydrolyse sphingomyelin to ceramide, rather than enzymes involved in de novo ceramide synthesis, were higher in inflamed compared to non-inflamed adipose tissue of obese women (with high and normal liver fat contents respectively). Sphingomyelinases were localised to both macrophages and adipocytes, but also to blood vessels and to extracellular regions surrounding vessels within adipose tissue. Expression levels of SMPD3 mRNA correlated significantly with concentrations of different ceramides and sphingomyelins. In both non-obese and obese subjects SMPD3 mRNA levels were higher in the more inflamed intra-abdominal compared to the subcutaneous adipose tissue depot.CONCLUSIONS: Generation of ceramides within adipose tissue as a result of sphingomyelinase action may contribute to inflammation in human adipose tissue.
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| 4. |
- Kolak, Mia, et al.
(författare)
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Immigrant men 's perceptions and experiences of accompanying their partner for contraceptive counselling provided by midwives in Sweden : a qualitative study
- 2024
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMale involvement in maternal health care has proven to be beneficial for improving maternal and child health and is often crucial in areas of family planning and contraceptive use. However, compared to male involvement in maternal health care, male involvement in contraceptive counselling is complex and controversial and thus faces certain challenges. Immigrant men in Sweden are often accompanying their partner for contraceptive counselling. Little is known about their presence and role.AimTo explore how immigrant men from the Middle East and Afghanistan perceive and experience accompanying their partner for contraceptive counselling provided by midwives in Sweden.MethodsInductive qualitative content analysis guided the interpretation of data based on 21 individual in-depth interviews.FindingsBalancing conflicting values and norms about sexual and reproductive health and rights including family planning was challenging and confusing when living in Sweden. Contraceptive counselling was perceived as a joint visit, and men were often acting as decision makers. The midwife's role as a contraceptive counsellor was perceived as trusted, but knowledge was lacking about the Swedish midwifery model and the Swedish healthcare system. Providers' ways of communicating sensitive information were crucial. Without marriage contraceptive counselling was unthinkable.ConclusionHighlighting male engagement and including men's sexual and reproductive health at policy levels are necessary for improving women's sexual and reproductive health and rights. Additional and new ways of contraceptive counselling and midwifery services, such as outreach work and joint visits, are needed in order to reach both men and women.
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| 5. |
- Sjögren, Per, et al.
(författare)
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Functional changes in adipose tissue in a randomised controlled trial of physical activity
- 2012
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Ingår i: Lipids in Health and Disease. - 1476-511X. ; 11, s. 80-
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Tidskriftsartikel (refereegranskat)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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