The concentration of hexosamine, a marker for mucin, was determined and related to the degree ofc... more The concentration of hexosamine, a marker for mucin, was determined and related to the degree ofcholesterol saturation and to the occurrence of cholesterol crystals in gall bladder bile of gall stone patients (n=40) and gall stone free subjects (n=25). Ten of the gall stone patients had been treated with chenodeoxycholic acid (CDCA) and eight with ursodeoxycholic acid (UDCA) three to four weeks before cholecystectomy. The hexosamine content was significantly higher in gall stone patients (137 (19) ng/ml, mean (SE) than in gall stone free subjects (83 (9) ng/ml, p<002). Treatment with CDCA or UDCA decreased cholesterol saturation, but did not significantly affect the hexosamine concentration. There was no difference in hexosamine concentration between gall stone patients with and without cholesterol crystals. The results do not support the hypothesis that the degree of cholesterol saturation is important for the mucin content of gall bladder bile in man. Neither do the data indicate that the formation and occurrence of cholesterol crystals in gall bladder bile from gall stone patients is caused by an increased concentration of mucin. As the studies were conducted on patients who had already had gall stones for several years, however, an effect of mucin in the very early stage of gall stone formation cannot be completely excluded.
bioRxiv (Cold Spring Harbor Laboratory), May 26, 2021
Male and female offspring of obese mothers are known to differ significantly in their metabolic a... more Male and female offspring of obese mothers are known to differ significantly in their metabolic adaptation and later development of complications. We investigated the sex-dependent responses in obese offspring of mice with maternal obesity, focusing on changes in liver glucose and lipid metabolism. Maternal obesity prior to and during gestation led to hepatic insulin resistance and inflammation in male offspring, while female offspring were protected. These sex differences were explained by more efficient transcriptional and posttranscriptional reprogramming of metabolic pathways to prevent the damaging effects of maternal obesity in females compared to males. These differences were sustained later in life, resulting in a better metabolic balance in female offspring. In conclusion, sex and maternal obesity drive transcriptional and posttranscriptional regulation of major metabolic processes in offspring liver differently, explaining the sexual dimorphism in obesity-associated metabolic risk.
With the increasing prevalence of obesity in women of reproductive age, there is an urgent need t... more With the increasing prevalence of obesity in women of reproductive age, there is an urgent need to understand the metabolic impact on the fetus. Sex-related susceptibility to liver diseases has been demonstrated but the underlying mechanism remains unclear. Here we report that maternal obesity impacts lipid metabolism differently in female and male offspring. Males, but not females, gained more weight and had impaired insulin sensitivity when born from obese mothers compared to control. Although lipid mass was similar in the livers of female and male offspring, sex-specific modifications in the composition of fatty acids, triglycerides and phospholipids was observed. These overall changes could be linked to sexspecific regulation of genes controlling metabolic pathways. Our findings revised the current assumption that sex-dependent susceptibility to metabolic disorders is caused by sex-specific postnatal regulation and instead we provide molecular evidence supporting in utero metabolic adaptations in the offspring of obese mothers.
This study was supported by the Swedish Medical Research Council (19X-04793). Dr. Angelin is the ... more This study was supported by the Swedish Medical Research Council (19X-04793). Dr. Angelin is the recipient of a fellowship from the Ernst Klenk Foundation.
The aim of this investigation was to study the influence of chenodeoxycholic acid administration ... more The aim of this investigation was to study the influence of chenodeoxycholic acid administration on cholesterol and bile acid synthesis in germ-free rats. Seven rats were fed a basal diet and 2 groups of 4 rats received the same diet supplemented with 0.4 and 1% chenodeoxycholic acid, respectively. After 6 weeks, feces were collected in one 3-and one 4-day pool for analysis of cholesterol and bile acids. When the sampling period was f'mished, the rats were killed and the liver microsomal fractions isolated. The activities of HMG CoA reductase and cholesterol 7~-hydroxylase were determined, the 7c~-hydroxylase by a mass fragmentographic method. The 2 dominating bile acids in the untreated rats were cholic acid and &muricholic acid. During treatment with chenodeoxycholic acid, 60-70% of this bile acid was converted into c~-and #-muricholic acid, indicating a high activity of the 6/3-hydroxylase. The excretion of cholic acid was almost completely inhibited and the 7c~-hydroxylase activity was decreased ca 75% in the rats fed 1% chenodeoxycholic acid. The activity of the hepatic HMG CoA reductase was unchanged. The fecal excretion of cholesterol increased 2-3 times. An accumulation of cholesterol was seen in the rats treated with 1% chenodeoxycholic acid, which was probably a result of the decreased catabolism of cholesterol to bile acids.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Arginase inhibition improves endothelial function in patients with familial hypercholesterolaemia... more Arginase inhibition improves endothelial function in patients with familial hypercholesterolaemia irrespective of their cholesterol levels.
Objectives.To investigate haemostatic markers (especially fibrinolysis), inflammatory parameters ... more Objectives.To investigate haemostatic markers (especially fibrinolysis), inflammatory parameters and lipids in patients with stable angina pectoris. Special attention was paid to differences between male and female patients, and to the reactivity to exercise or the diurnal variation of certain parameters. Subjects. Eight hundred and nine patients (31% females) and a matched healthy control group (n = 50). Results. The patients had signs of disturbed fibrinolysis, with elevated plasma levels of tissue plasminogen activator (tPA) antigen and plasminogen activator inhibitor (PAI‐1) activity at rest, and attenuated responses of tPA antigen and activity to exercise. Elevated levels of fibrinogen, white blood cell counts and orosomucoid were found, suggesting increased inflammatory activity, as well as a more disturbed lipid profile (higher triglycerides and lower HDL cholesterol levels) than among controls. Female patients had higher HDL cholesterol and lower triglyceride levels than male patients, but higher platelet counts and signs of enhanced platelet activity (β‐thromboglobulin excretion). In addition, female patients had lower white blood cell counts, suggesting lesser inflammatory activity. Conclusions. Patients with stable angina pectoris have signs of markedly disturbed fibrinolysis both at rest and in response to exercise, as well as signs of enhanced inflammatory activity and dyslipidemia. The observed sex differences suggest that male patients with stable angina pectoris may have a more lipid‐related disease, whereas it may be more dependent on platelet function in females.
Eating behavior and food‐related decision making are among the most complex of the motivated beha... more Eating behavior and food‐related decision making are among the most complex of the motivated behaviors, and understanding the neurobiology of eating behavior, and its developmental dynamics, is critical to advancing the nutritional sciences and public health. Recent advances from both human and animal studies are revealing that individual capacity to make health‐promoting food decisions varies based on biological and physiological variation in the signaling pathways that regulate the homeostatic, hedonic, and executive functions; past developmental exposures and current life‐stage; the food environment; and complications of chronic disease that reinforce the obese state. Eating rate drives increased calorie intake and represents an important opportunity to lower rates of food consumption and energy intake through product reformulation. Understanding human eating behaviors and nutrition in the context of neuroscience can strengthen the evidence base from which dietary guidelines are derived and can inform policies, practices, and educational programs in a way that increases the likelihood they are adopted and effective for reducing rates of obesity and other diet‐related chronic disease.
Different plasma lipoprotein fractions in physiological concentrations have opposite effects on t... more Different plasma lipoprotein fractions in physiological concentrations have opposite effects on the phagocytosis and migration of human neutrophilic granulocytes. Preincubation for half an hour with very low density lipoproteins decreased the phagocytosis as well as the chemotactic and random migrations of the cells, while preincubation with high density lipoproteins increased the same functions. No effects were seen with low density lipoproteins. It is suggested that disturbances in plasma lipoprotein pattern may affect the function of phagocytes.
The concentration of hexosamine, a marker for mucin, was determined and related to the degree ofc... more The concentration of hexosamine, a marker for mucin, was determined and related to the degree ofcholesterol saturation and to the occurrence of cholesterol crystals in gall bladder bile of gall stone patients (n=40) and gall stone free subjects (n=25). Ten of the gall stone patients had been treated with chenodeoxycholic acid (CDCA) and eight with ursodeoxycholic acid (UDCA) three to four weeks before cholecystectomy. The hexosamine content was significantly higher in gall stone patients (137 (19) ng/ml, mean (SE) than in gall stone free subjects (83 (9) ng/ml, p<002). Treatment with CDCA or UDCA decreased cholesterol saturation, but did not significantly affect the hexosamine concentration. There was no difference in hexosamine concentration between gall stone patients with and without cholesterol crystals. The results do not support the hypothesis that the degree of cholesterol saturation is important for the mucin content of gall bladder bile in man. Neither do the data indicate that the formation and occurrence of cholesterol crystals in gall bladder bile from gall stone patients is caused by an increased concentration of mucin. As the studies were conducted on patients who had already had gall stones for several years, however, an effect of mucin in the very early stage of gall stone formation cannot be completely excluded.
bioRxiv (Cold Spring Harbor Laboratory), May 26, 2021
Male and female offspring of obese mothers are known to differ significantly in their metabolic a... more Male and female offspring of obese mothers are known to differ significantly in their metabolic adaptation and later development of complications. We investigated the sex-dependent responses in obese offspring of mice with maternal obesity, focusing on changes in liver glucose and lipid metabolism. Maternal obesity prior to and during gestation led to hepatic insulin resistance and inflammation in male offspring, while female offspring were protected. These sex differences were explained by more efficient transcriptional and posttranscriptional reprogramming of metabolic pathways to prevent the damaging effects of maternal obesity in females compared to males. These differences were sustained later in life, resulting in a better metabolic balance in female offspring. In conclusion, sex and maternal obesity drive transcriptional and posttranscriptional regulation of major metabolic processes in offspring liver differently, explaining the sexual dimorphism in obesity-associated metabolic risk.
With the increasing prevalence of obesity in women of reproductive age, there is an urgent need t... more With the increasing prevalence of obesity in women of reproductive age, there is an urgent need to understand the metabolic impact on the fetus. Sex-related susceptibility to liver diseases has been demonstrated but the underlying mechanism remains unclear. Here we report that maternal obesity impacts lipid metabolism differently in female and male offspring. Males, but not females, gained more weight and had impaired insulin sensitivity when born from obese mothers compared to control. Although lipid mass was similar in the livers of female and male offspring, sex-specific modifications in the composition of fatty acids, triglycerides and phospholipids was observed. These overall changes could be linked to sexspecific regulation of genes controlling metabolic pathways. Our findings revised the current assumption that sex-dependent susceptibility to metabolic disorders is caused by sex-specific postnatal regulation and instead we provide molecular evidence supporting in utero metabolic adaptations in the offspring of obese mothers.
This study was supported by the Swedish Medical Research Council (19X-04793). Dr. Angelin is the ... more This study was supported by the Swedish Medical Research Council (19X-04793). Dr. Angelin is the recipient of a fellowship from the Ernst Klenk Foundation.
The aim of this investigation was to study the influence of chenodeoxycholic acid administration ... more The aim of this investigation was to study the influence of chenodeoxycholic acid administration on cholesterol and bile acid synthesis in germ-free rats. Seven rats were fed a basal diet and 2 groups of 4 rats received the same diet supplemented with 0.4 and 1% chenodeoxycholic acid, respectively. After 6 weeks, feces were collected in one 3-and one 4-day pool for analysis of cholesterol and bile acids. When the sampling period was f'mished, the rats were killed and the liver microsomal fractions isolated. The activities of HMG CoA reductase and cholesterol 7~-hydroxylase were determined, the 7c~-hydroxylase by a mass fragmentographic method. The 2 dominating bile acids in the untreated rats were cholic acid and &muricholic acid. During treatment with chenodeoxycholic acid, 60-70% of this bile acid was converted into c~-and #-muricholic acid, indicating a high activity of the 6/3-hydroxylase. The excretion of cholic acid was almost completely inhibited and the 7c~-hydroxylase activity was decreased ca 75% in the rats fed 1% chenodeoxycholic acid. The activity of the hepatic HMG CoA reductase was unchanged. The fecal excretion of cholesterol increased 2-3 times. An accumulation of cholesterol was seen in the rats treated with 1% chenodeoxycholic acid, which was probably a result of the decreased catabolism of cholesterol to bile acids.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Arginase inhibition improves endothelial function in patients with familial hypercholesterolaemia... more Arginase inhibition improves endothelial function in patients with familial hypercholesterolaemia irrespective of their cholesterol levels.
Objectives.To investigate haemostatic markers (especially fibrinolysis), inflammatory parameters ... more Objectives.To investigate haemostatic markers (especially fibrinolysis), inflammatory parameters and lipids in patients with stable angina pectoris. Special attention was paid to differences between male and female patients, and to the reactivity to exercise or the diurnal variation of certain parameters. Subjects. Eight hundred and nine patients (31% females) and a matched healthy control group (n = 50). Results. The patients had signs of disturbed fibrinolysis, with elevated plasma levels of tissue plasminogen activator (tPA) antigen and plasminogen activator inhibitor (PAI‐1) activity at rest, and attenuated responses of tPA antigen and activity to exercise. Elevated levels of fibrinogen, white blood cell counts and orosomucoid were found, suggesting increased inflammatory activity, as well as a more disturbed lipid profile (higher triglycerides and lower HDL cholesterol levels) than among controls. Female patients had higher HDL cholesterol and lower triglyceride levels than male patients, but higher platelet counts and signs of enhanced platelet activity (β‐thromboglobulin excretion). In addition, female patients had lower white blood cell counts, suggesting lesser inflammatory activity. Conclusions. Patients with stable angina pectoris have signs of markedly disturbed fibrinolysis both at rest and in response to exercise, as well as signs of enhanced inflammatory activity and dyslipidemia. The observed sex differences suggest that male patients with stable angina pectoris may have a more lipid‐related disease, whereas it may be more dependent on platelet function in females.
Eating behavior and food‐related decision making are among the most complex of the motivated beha... more Eating behavior and food‐related decision making are among the most complex of the motivated behaviors, and understanding the neurobiology of eating behavior, and its developmental dynamics, is critical to advancing the nutritional sciences and public health. Recent advances from both human and animal studies are revealing that individual capacity to make health‐promoting food decisions varies based on biological and physiological variation in the signaling pathways that regulate the homeostatic, hedonic, and executive functions; past developmental exposures and current life‐stage; the food environment; and complications of chronic disease that reinforce the obese state. Eating rate drives increased calorie intake and represents an important opportunity to lower rates of food consumption and energy intake through product reformulation. Understanding human eating behaviors and nutrition in the context of neuroscience can strengthen the evidence base from which dietary guidelines are derived and can inform policies, practices, and educational programs in a way that increases the likelihood they are adopted and effective for reducing rates of obesity and other diet‐related chronic disease.
Different plasma lipoprotein fractions in physiological concentrations have opposite effects on t... more Different plasma lipoprotein fractions in physiological concentrations have opposite effects on the phagocytosis and migration of human neutrophilic granulocytes. Preincubation for half an hour with very low density lipoproteins decreased the phagocytosis as well as the chemotactic and random migrations of the cells, while preincubation with high density lipoproteins increased the same functions. No effects were seen with low density lipoproteins. It is suggested that disturbances in plasma lipoprotein pattern may affect the function of phagocytes.
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