Childbearing decreases HDL-cholesterol, potentially contributing to the increased risk of CVD in parous women. Large HDL particles (HDL-P) are associated with lower risk of CVD. In this secondary ...analysis of a randomised controlled trial, we investigated the effects of 12-week dietary and exercise treatments on HDL-P subclass concentration, size and apoA1 in lactating women with overweight/obesity. At 10–14 weeks postpartum, 68 women with pre-pregnant BMI 25–35 kg/m2 were randomised to four groups using 2 × 2 factorial design: (1) dietary treatment for weight loss; (2) exercise treatment; (3) both treatments and (4) no treatment. Lipoprotein subclass profiling by NMR spectroscopy was performed in serum at randomisation and after 3 and 12 months, and the results analysed with two-way ANCOVA. Lipid concentrations decline naturally postpartum. At 3 months (5–6 months postpartum), both diet (P = 0·003) and exercise (P = 0·008) reduced small HDL-P concentration. Concurrently, exercise limited the decline in very large HDL-P (P = 0·002) and the effect was still significant at 12 months (15 months postpartum) (P = 0·041). At 12 months, diet limited the decline in very large HDL-P (P = 0·005), large HDL-P (P = 0·001) and apoA1 (P = 0·002) as well as HDL size (P = 0·002). The dietary treatment for weight loss and the exercise treatment both showed effects on HDL-P subclasses in lactating women with overweight and obesity possibly associated with lower CVD risk. The dietary treatment had more effects than the exercise treatment at 12 months, likely associated with a 10 % weight loss.
Obesity is associated with increased muscle mass and muscle strength. Methods taking into account the total body mass to reveal obese older individuals at increased risk of functional impairment are ...needed. Therefore, we aimed to detect methods to identify obese older adults at increased risk of functional impairment. Home-dwelling older adults (
417, ≥ 70 years of age) were included in this cross-sectional study. Sex-specific cut-off points for two obesity phenotypes (waist circumference (WC) and body fat mass (FM %)) were used to divide women and men into obese and non-obese groups, and within-sex comparisons were performed. Obese women and men, classified by both phenotypes, had similar absolute handgrip strength (HGS) but lower relative HGS (HGS/total body mass) (
< 0·001) than non-obese women and men, respectively. Women with increased WC and FM %, and men with increased WC had higher appendicular skeletal muscle mass (
< 0·001), lower muscle quality (HGS/upper appendicular muscle mass) (
< 0·001), and spent longer time on the stair climb test and the repeated sit-to-stand test (
< 0·05) than non-obese women and men, respectively. Absolute muscle strength was not able to discriminate between obese and non-obese older adults. However, relative muscle strength in particular, but also muscle quality and physical performance tests, where the total body mass was taken into account or served as an extra load, identified obese older adults at increased risk of functional impairment. Prospective studies are needed to determine clinically relevant cut-off points for relative HGS in particular.
The primary objective was to study the risk of acute myocardial infarction (AMI) and coronary heart disease (CHD) in patients with familial hypercholesterolaemia (FH) and compare with the risk in the ...general population.
Patients with an FH mutation but without prior AMI (n=3071) and without prior CHD (n=2795) were included in the study sample during 2001-2009. We obtained data on all AMI and CHD hospitalisations in Norway. We defined incident cases as first time hospitalisation or out-of-hospital death due to AMI or CHD. We estimated standardised incidence ratios (SIRs) with 95% CIs with indirect standardisation using incidence rates for the total Norwegian population stratified by sex, calendar year and 1 year age groups as reference rates.
SIRs for AMI (95% CIs) were highest in the age group 25-39 years; 7.5 (3.7 to 14.9) in men and 13.6 (5.1 to 36.2) in women and decreased with age to 0.9 (0.4 to 2.1) in men and 1.8 (0.9 to 3.7) in women aged 70-79 years. Similarly, SIRs for CHD were highest among patients 25-39 years old; 11.1 (7.1-17.5) in men and 17.3 (9.6-31.2) in women and decreased 2.4 (1.4-4.2) in men and 3.2 (1.5-7.2) in women at age 70-79. For all age groups, combined SIRs for CHD were 4.2 (3.6-5.0) in men and 4.7 (3.9-5.7) in women.
Patients with FH are at severely increased risk of AMI and CHD compared with the general population. The highest excess risk was in the youngest group aged 25-39 years, in both sexes.
Abstract
Follistatin-like protein 1 (Fstl1) is a secreted glycoprotein of the follistatin family. Fstl1 is secreted by C2C12 cells, and Akt1 over-expression in skeletal muscle leads to its induction ...in muscle and increased circulating levels. So far, secretion of Fstl1 by human myotubes and the effect of exercise on its circulating levels have not been investigated. Here, we examined both the regulation of Fstl1 expression and secretion in primary human skeletal muscle cells and the effect of acute exercise on Fstl1 serum concentrations in humans. We show that human myotubes express and secrete Fstl1 in a differentiation-dependent manner. Furthermore, IFNγ and IL-1β significantly increase Fstl1 secretion. Electrical pulse stimulation (EPS)-induced contractile activity of myotubes did not regulate Fstl1. Interestingly, we observed that 60 min cycling increased serum Fstl1 level by 22%. In conclusion, we demonstrate that Fstl1 is expressed and secreted by human myotubes and plasma Fstl1 levels are increased after exercise.
Purpose
By-products from farmed fish contain large amounts of proteins and may be used for human consumption. The purpose of this study was to investigate cardiometabolic effects and metabolic ...tolerance in mice consuming fishmeal from salmon by-products, salmon filet or beef.
Methods
Female C57BL/6J mice were fed chow, as a healthy reference group, or a high-fat diet for 10 weeks to induce obesity and glucose intolerance. Obese mice were subsequently given isocaloric diets containing 50% of the dietary protein from salmon fishmeal, salmon filet or beef for 10 weeks. Mice were subjected to metabolic phenotyping, which included measurements of body composition, energy metabolism in metabolic cages and glucose tolerance. Lipid content and markers of hepatic toxicity were determined in plasma and liver. Hepatic gene and protein expression was determined with RNA sequencing and immunoblotting.
Results
Mice fed fishmeal, salmon filet or beef had similar food intake, energy consumption, body weight gain, adiposity, glucose tolerance and circulating levels of lipids and hepatic toxicity markers, such as p-ALT and p-AST. Fishmeal increased hepatic cholesterol levels by 35–36% as compared to salmon filet (
p
= 0.0001) and beef (
p
= 0.005). This was accompanied by repressed expression of genes involved in steroid and cholesterol metabolism and reduced levels of circulating Pcsk9.
Conclusion
Salmon fishmeal was well tolerated, but increased hepatic cholesterol content. The high cholesterol content in fishmeal may be responsible for the effects on hepatic cholesterol metabolism. Before introducing fishmeal from salmon by-products as a dietary component, it may be advantageous to reduce the cholesterol content in fishmeal.
Introduction
Increased BMI has been identified as a risk factor for most pregnancy complications, but the underlying metabolic factors mediating the detrimental effects of BMI are largely unknown. We ...aimed to compare metabolic profiles in overweight/obese women (body mass index BMI ≥ 25 kg/m2) and normal weight/underweight women (BMI < 25 kg/m2) across gestation. We also explored how gestational weight gain (GWG) affected maternal metabolic profiles.
Material and methods
Exploratory nested case–control study based on a prospective longitudinal cohort of women who were healthy prior to pregnancy and gave birth at Oslo University Hospital from 2002 to 2008. The sample consisted of 48 women who were overweight/obese and 59 normal‐weight/underweight women. Plasma samples from four time points in pregnancy (weeks 14–16, 22–24, 30–32 and 36–38) were analyzed by nuclear magnetic resonance spectroscopy and 91 metabolites were measured. Linear regression models were fitted for each of the metabolites at each time point.
Results
Overweight or obese women had higher levels of lipids in very‐low‐density lipoprotein (VLDL), total triglycerides, triglycerides in VLDL, total fatty acids, monounsaturated fatty acids, saturated fatty acids, leucine, valine, and total branched‐chain amino acids in pregnancy weeks 14–16 compared to underweight and normal‐weight women. Docosahexaenoic acid and degree of unsaturation were significantly lower in overweight/obese women in pregnancy weeks 36–38. In addition, overweight or obese women had higher particle concentration of XXL‐VLDL and glycoprotein acetyls (GlycA) at weeks 14–16 and 30–32. GWG did not seem to affect the metabolic profile, regardless of BMI group when BMI was treated as a dichotomous variable, ≥25 kg/m2 (yes/no).
Conclusions
Overweight or obese women had smaller pregnancy‐related metabolic alterations than normal‐weight/underweight women. There was a trend toward higher triglyceride and VLDL particle concentration in overweight/obese women. As this was a hypothesis‐generating study, the similarities with late‐onset pre‐eclampsia warrant further investigation. The unfavorable development of fatty acid composition in overweight/obese women, with possible implication for the offspring, should also be studied further in the future.
Overweight or obese women had elevated levels of most lipid‐related measures in early pregnancy, but the differences were attenuated from weeks 22–24. Particle concentration of very‐low‐density lipoprotein and GlycA were increased throughout pregnancy in overweight or obese women meanwhile the ratio of polyunsaturated fatty acids to total fatty acids (in particular docosahexaenoic acid) were decreased. Regardless of BMI group, gestational weight gain did not affect the metabolic profile.
Proteins secreted by skeletal muscle, so called myokines, have been shown to affect muscle physiology and additionally exert systemic effects on other tissues and organs. Although recent profiling ...studies have identified numerous myokines, the amount of overlap from these studies indicates that the secretome of skeletal muscle is still incompletely characterized. One limitation of the models used is the lack of contraction, a central characteristic of muscle cells. Here we aimed to characterize the secretome of primary human myotubes by cytokine antibody arrays and to identify myokines regulated by contraction, which was induced by electrical pulse stimulation (EPS). In this study, we validated the regulation and release of two selected myokines, namely pigment epithelium derived factor (PEDF) and dipeptidyl peptidase 4 (DPP4), which were recently described as adipokines. This study reveals that both factors, DPP4 and PEDF, are secreted by primary human myotubes. PEDF is a contraction-regulated myokine, although PEDF serum levels from healthy young men decrease after 60 min cycling at VO2max of 70%. Most interestingly, we identified 52 novel myokines which have not been described before to be secreted by skeletal muscle cells. For 48 myokines we show that their release is regulated by contractile activity. This profiling study of the human skeletal muscle secretome expands the number of myokines, identifies novel contraction-regulated myokines and underlines the overlap between proteins which are adipokines as well as myokines.
The effects of a low carbohydrate/high fat (LCHF) diet on health are debated. This study aims to explore the effects of a diet with less than 20 g carbohydrates per day (LCHF) on plasma low density ...lipoprotein cholesterol (LDL-C) in young and healthy adults. The secondary aim is the assessment of lipid profile and peripheral blood mononuclear cells (PBMC) gene expression.
This was a randomized controlled parallel-designed intervention study. Participants were either assigned to a three-week LCHF diet or a control group continuing habitual diet ad libitum, in both groups.
In total, 30 healthy normal weight participants completed the study. Nine subjects did not complete it due to adverse events or withdrawn consent. In the LCHF diet group (n = 15), plasma LDL-C increased from (mean ± SD) 2.2 ± 0.4 mmol/l before intervention to 3.1 ± 0.8 after, while in the control group (n = 15), LDL-C remained unchanged: 2.5 ± 0.8 mmol/l (p < 0.001 between groups). There was a significant increase in apolipoprotein B, total cholesterol, high-density lipoprotein cholesterol, free fatty acids, uric acid and urea in the LCHF group versus controls. Plasma levels of triglycerides, lipoprotein (a), glucose, C-peptide or C-reactive protein (CRP), blood pressure, body weight or body composition did not differ between the groups. PBMC gene expression of sterol regulator element binding protein 1 (SREBP-1) was increased in the LCHF group versus controls (p ≤ 0.01). The individual increase in LDL-C from baseline varied between 5 and 107% in the LCHF group.
An LCHF diet for three weeks increased LDL-C with 44% versus controls. The individual response on LCHF varied profoundly.
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•Low carbohydrate/high fat (LCHF) diet for three weeks increased LDL-cholesterol (LDL-C) with 44% versus controls.•The response to LCHF diet varied between the individuals from no more than 5% increase in LDL-C and up to a 107% increase.•The unpredictable individual response to the LCHF diet suggest that LDL-C should be measured in people using an LCHF diet.
Avian eggshell membrane (ESM) is a complex extracellular matrix comprising collagens, glycoproteins, proteoglycans, and hyaluronic acid. We have previously demonstrated that ESM possesses ...anti-inflammatory properties
and regulates wound healing processes
. The present study aimed to investigate if oral intake of micronized ESM could attenuate skeletal muscle aging associated with beneficial alterations in gut microbiota profile and reduced inflammation.
Elderly male C57BL/6 mice were fed an AIN93G diet supplemented with 0, 0.1, 1, or 8% ESM. Young mice were used as reference. The digestibility of ESM was investigated using the static
digestion model INFOGEST for older people and adults, and the gut microbiota profile was analyzed in mice. In addition, we performed a small-scale pre-clinical human study with healthy home-dwelling elderly (>70 years) who received capsules with a placebo or 500 mg ESM every day for 4 weeks and studied the effect on circulating inflammatory markers.
Intake of ESM in elderly mice impacted and attenuated several well-known hallmarks of aging, such as a reduction in the number of skeletal muscle fibers, the appearance of centronucleated fibers, a decrease in type IIa/IIx fiber type proportion, reduced gene expression of satellite cell markers
and
and increased gene expression of the muscle atrophy marker
Similarly, a transition toward the phenotypic characteristics of young mice was observed for several proteins involved in cellular processes and metabolism. The digestibility of ESM was poor, especially for the elderly condition. Furthermore, our experiments showed that mice fed with 8% ESM had increased gut microbiota diversity and altered microbiota composition compared with the other groups. ESM in the diet also lowered the expression of the inflammation marker TNFA in mice and
in THP-1 macrophages. In the human study, intake of ESM capsules significantly reduced the inflammatory marker CRP. Altogether, our results suggest that ESM, a natural extracellular biomaterial, may be attractive as a nutraceutical candidate with a possible effect on skeletal muscle aging possibly through its immunomodulating effect or gut microbiota.
Background Homozygous familial hypercholesterolemia (HoFH), which affects 1 in a million individuals, leads to extremely elevated levels of cholesterol and early-onset cardiovascular disease. ...Objective The aim of this study was to assess all 7 HoFH patients treated with low-density lipoprotein (LDL) apheresis in Norway with respect to quality of life, clinical and laboratory assessments, and cardiovascular status. Methods Apheresis treatment and assessment of cardiovascular status was performed at local hospitals but coordinated by the Lipid Clinic that has followed all patients since diagnosis. Quality of life was evaluated by a validated questionnaire. Results Results are shown as median (min-max). LDL cholesterol at diagnosis (untreated) was 704 (592–1268) mg/dL (18.2 15.3–32.8 mmol/L). Medication was initiated at age 9 (2–35) years, and apheresis treatment at age 10 (6–44) years. Regular once-weekly apheresis combined with the maximum-tolerable doses of a statin and ezetimibe reduced LDL cholesterol to 197 (170–282) mg/dL (5.1 4.5–7.3 mmol/L) pre-apheresis and 85 (50–108) mg/dL (2.2 1.3–2.8 mmol/L) post-apheresis. Calculated interval mean LDL cholesterol was 162 (135–220) mg/dL (4.2 3.5–5.7 mmol/L). Duration of apheresis treatment was 11 (1–24) years. Cardiovascular manifestations progressed in most patients despite the apheresis treatment. The subjects’ quality of life was comparable with that of a healthy population, with the exception of two patients, who were significantly affected by coronary disease. Conclusions Well-tolerated, once-weekly LDL apheresis achieves lower interval mean LDL cholesterol levels between apheresis treatments than previously reported for apheresis every second week. However, progressions of cardiovascular manifestations still occurred, which highlights the importance of earlier and even more aggressive treatment and follow-up in HoFH.
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