Serum Cholesterol Measurements Research Articles

Cholesterol biosensor based on inkjet-printed Prussian blue nanoparticle-modified screen-printed electrodes

Here we describe the construction and optimization of a cholesterol biosensor based on screen-printed electrodes (SPEs) modified with inkjet-printed Prussian blue nanoparticles (PBNPs). The deposition of PBNPs using inkjet printing led to the highly facile fabrication of sensors with excellent sensitivity and reproducibility for the measurement of H2O2. Further integration of the sensor with a microfabricated low volume (4μL) sample cell allowed the measurement of cholesterol in serum with the addition of cholesterol oxidase. The biosensor exhibited a sensitivity to cholesterol of 2.1μA/mMcm2 (r2=0.97, n=5) and was linear in the range of 0–15mM.

A strategy focused on MAPT, APP, NCSTN and BACE1 to build blood classifiers for Alzheimer׳s disease

BackgroundAlthough Alzheimer׳s disease (AD) is a brain disorder, a number of peripheral alterations have been found in these patients, including differences in leukocyte gene expression; however, the key genes involved in plaque and tangle formation have shown a relatively small potential as diagnostic markers. We focused on MAPT, APP, NCSTN and BACE1 as the basis to build and compare blood classifiers for AD. MethodsWe used a combined model to build disease classifiers, using measures of blood pressure and serum glucose, cholesterol and triglyceride levels as well as RT-PCR expression levels of APP, NCSTN and BACE1 in peripheral blood mononuclear cells (PBMCs) from an independent cohort of 36 individuals of cognitively-normal controls, AD and other neuropathologies. Also, a set of genes was carefully selected by molecular interactions with MAPT, APP, NCSTN and BACE1 to test an expression-based classifier in a public microarray dataset of 40 samples (AD and controls). A series of discriminant analyses and classification and regression trees (C&RTs) were used to perform classification tasks. ResultsUsing C&RTs, the combined model showed potential to differentially diagnose AD with up to 94.4% accuracy and 100% specificity for our independent sample. Furthermore, a subset of 16 genes showed the best diagnostic potential using a minimum number of expression variables, correctly classifying up to 100% of samples in the public dataset. ConclusionsOur unique method of variable selection proves that even elements showing no significant differences between controls and AD, but that have somehow been linked to AD or AD-related elements, still hold a potential to be used in its diagnosis. Sample size and inherent methodological limitations of this study need to be kept in mind. Our classifiers require careful further testing in larger cohorts. Nonetheless, we believe these results provide evidence for the utility of our innovative method, which contributes a different approach to generate promising diagnostic tools for neuropsychiatric disorders.

Abstract P220: Sustained Disparity in Ever Having Received a Serum Cholesterol Measurement by Educational Level among US Adults, 1999-2012

Background: A previous study showed that lower educational level was significantly associated with less likelihood of ever having received a serum cholesterol test among US adults during 1999-2002. No study, however, has examined the time trends after 2002. Objectives: To examine whether disparity by educational level in lifetime receipt of a serum cholesterol test persisted in the US from 1999 through 2012. Methods: A serial cross-sectional study in a nationally representative sample of 29,662 US adults from the National Health and Nutrition Examination Survey, 1999-2012. We excluded those had coronary heart disease and/or diabetes. The lifetime history of having had a serum test for cholesterol and educational level were asked in the interview. Educational level was grouped as greater than high school (HS), HS, or less than HS. We investigated time trends of lifetime cholesterol measurement by educational level, using a logistic regression model that included interaction terms between survey period and educational level, adjusted for covariates. Results: In 1999-2000, the proportion of ever having had a serum cholesterol test was significantly lower for participants with less education (greater than HS: 76.2%, HS: 62.0%, less than HS: 51.4%). In 2011-2012, the pattern of lifetime testing by educational level was similar to the initial period (greater than HS: 77.5%, HS: 67.5%, less than HS: 55.4%). Although the uptake of cholesterol testing significantly increased over the survey period among the less-than-HS group, the difference in trends across the three groups was not significant. Conclusions: The difference by educational level in lifetime serum cholesterol measurement observed in 1999-2002 persisted through 2011-2012. Public health policy should focus on increasing the uptake of serum cholesterol test and early detection of hypercholesterolemia, particularly among people with lower educational level. Figure. Trends of lifetime serum cholesterol measurement by educational level among US adults, 1999-2012

Lowering of cholesterol bioaccessibility and serum concentrations by saponins: in vitro and in vivo studies.

Using an in vitro digestion model, we studied the effect of six saponin extracts on the bioaccessibility of cholesterol and saturated fatty acids (SFAs). In the absence of saponins, around 78% of the available cholesterol was solubilized in the simulated intestinal fluids. The addition of two extracts, Quillaja Dry (QD) and Sapindin (SAP), was found to decrease cholesterol bioaccessibility to 19% and 44%, respectively. For both extracts, the main mechanism of this effect is the displacement of cholesterol molecules from the bile salt micelles, leading to formation of cholesterol precipitates that cannot pass through the mucus layer of the intestine. QD decreased strongly the SFA bioaccessibility as well, from 69 to 9%, due to formation of calcium-SFA precipitates, while SAP had no effect on SFA. We studied the in vivo activity of QD and SAP extracts by measuring serum cholesterol in mice fed with experimental diets within a 7-day period. Both extracts were found to prevent dietary hypercholesterolemia in mice fed on a cholesterol-rich diet. The other saponin extracts did not show any significant effect in vitro and, therefore, were not studied in vivo. The cholesterol lowering ability of Sapindin extract is reported for the first time in the current study.

A metabolic view on menopause and ageing.

The ageing of the global population calls for a better understanding of age-related metabolic consequences. Here we report the effects of age, sex and menopause on serum metabolites in 26,065 individuals of Northern European ancestry. Age-specific metabolic fingerprints differ significantly by gender and, in females, a substantial atherogenic shift overlapping the time of menopausal transition is observed. In meta-analysis of 10,083 women, menopause status associates with amino acids glutamine, tyrosine and isoleucine, along with serum cholesterol measures and atherogenic lipoproteins. Among 3,204 women aged 40-55 years, menopause status associates additionally with glycine and total, monounsaturated, and omega-7 and -9 fatty acids. Our findings suggest that, in addition to lipid alterations, menopause may contribute to future metabolic and cardiovascular risk via influencing amino-acid concentrations, adding to the growing evidence of the importance of amino acids in metabolic disease progression. These observations shed light on the metabolic consequences of ageing, gender and menopause at the population level.

Body mass index, waist circumference and HOMA-IR correlate with the Psoriasis Area and Severity Index in patients with psoriasis receiving phototherapy

Funding sources: This work was funded by an unrestricted research grant from Merck Serono Ltd and Abbott Laboratories Ltd and the Postgraduate Medical and Dental Board of Ireland. Conflicts of interest: none declared. Dear Editor, An increased incidence of obesity in patients with psoriasis has been documented in cross‐sectional studies of large healthcare databases and case–control studies.1 2 3 4 5 6 7 Obesity, and in particular centripetal obesity, confers a risk of developing insulin resistance and type 2 diabetes, which in turn increases the risk of cardiovascular disease. Since 1978 it has been known that patients with psoriasis have higher rates of type 2 diabetes and cardiovascular disease and it is likely that this is driven by obesity and concomitant insulin resistance. We undertook a study to establish the effect of body mass index (BMI), abdominal obesity and insulin resistance on psoriasis severity and Framingham risk. Following ethical approval, consecutive patients with psoriasis, aged ≥ 18 years, were recruited prior to commencing phototherapy or photochemotherapy (TL‐01 or psoralen plus ultraviolet A) between October 2008 and July 2011. Patients had a full physical examination and the Psoriasis Area and Severity Index (PASI) score was recorded. Height, weight and waist circumference were measured for each patient. The BMI was calculated using the formula: weight in kg/(height in m)2. Obesity was defined as a BMI > 30, overweight as BMI 25–30 and lean as a BMI < 25 according to the World Health Organization definition of obesity. Systolic blood pressure was measured using a sphygmomanometer on the left brachial artery. Fasting blood samples were taken for the measurement of insulin, glucose and serum cholesterol. Insulin resistance was measured using the homeostasis model with the formula: insulin × glucose/22·5 (HOMA‐IR, homeostatic model assessment–insulin resistance). Framingham risk was calculated using MedCalc® (MedCalc Software, Ostend, Belgium). Results were analysed using GraphPad Prism (GraphPad Software Inc., La Jolla, CA, U.S.A.), using Student's t‐test, anova and Pearson's rank correlation.

Serum cholesterol and cognitive functions: the Lothian Birth Cohort 1936.

We examined the associations between serum cholesterol measures, statin use, and cognitive function measured in childhood and in old age. The possibility that lifelong (trait) cognitive ability accounts for any cross-sectional associations between cholesterol and cognitive performance in older age, seen in observational studies, has not been tested to date. Participants were 1,043 men and women from the Lothian Birth Cohort 1936 Study, most of whom had participated in a nationwide IQ-type test in childhood (Scottish Mental Survey of 1947), and were followed up at about age 70 years. Serum cholesterol measures included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides, and cholesterol:HDL cholesterol ratio. Cognitive outcome measures were age 70 IQ (using the same test as at age 11 years), general cognitive ability (g), processing speed, memory, and verbal ability. Higher TC, higher HDL-C, and lower triglycerides were associated with higher age 70 cognitive scores in most cognitive domains. These relationships were no longer significant after covarying for childhood IQ, with the exception a markedly attenuated association between TC and processing speed, and triglycerides and age 70 IQ. In the fully adjusted model, all conventionally significant (p < 0.05) effects were removed. Childhood IQ predicted statin use in old age. Statin users had lower g, processing speed, and verbal ability scores at age 70 years after covarying for childhood IQ, but significance was lost after adjusting for TC levels. These results suggest that serum cholesterol and cognitive function are associated in older age via the lifelong stable trait of intelligence. Potential mechanisms, including lifestyle factors, are discussed.

Abstract P052: History of High Cholesterol and Incidence of Dementia: The 90+ Study

Background: Hypercholesterolemia at midlife has been associated with increased dementia risk. However, some studies suggest that this relationship may change with age. It is not known if an association between cholesterol and dementia incidence persists in the oldest-old (people aged 90+) [[Unable to Display Character: &amp;#8211;]] the most rapidly growing segment of the population. We examined whether a history of high cholesterol is associated with dementia incidence in The 90+ Study, a longitudinal population-based study of the oldest-old. Methods: We analyzed data from 569 participants who were non-demented at baseline, had one or more follow-up visits, and provided self-reported history of high cholesterol. Participants were evaluated every six months, with dementia diagnosis (DSM-IV criteria) at follow-up determined in a hierarchal manner from: neurological exam, Mini-Mental Status Exam, informant questionnaires, and the Cognitive Abilities Screening Instrument (telephone short form). We used Cox regression to estimate the association between history of high cholesterol and incident dementia, using age as the time scale and adjusting for gender and education. Results: Participants had a mean age of 93.3 years (range 90-103) at baseline and were primarily Caucasian (99%), women (69%), and with at least some college education (77%). 200 participants (35%) reported a history of high cholesterol. After a mean follow-up of 3.3 years (range 0.1-9.0), 224 individuals (39%) were diagnosed with dementia (68% from neurological exam). People who reported a history of high cholesterol at baseline were less likely to develop dementia compared to people without a history of high cholesterol (HR=0.76, 95% CI 0.57[[Unable to Display Character: &amp;#8211;]]1.02, p=0.072). Conclusions: Contrary to findings in younger ages, high cholesterol appears to be associated with lower dementia risk in the oldest-old. A potential mechanism could be that with advanced age a compensatory increase in cholesterol synthesis or uptake occurs in order to preserve function of the aging brain, as the cholesterol molecule has a variety of biological roles related to brain health. Further research is needed to analyze direct measurements of serum cholesterol, as well as to examine the effects of a variety of factors (such as use and duration of cholesterol-lowering medications, low cholesterol as a proxy for poor health and frailty, and duration of hypercholesterolemia) on the observed association. Our results imply that target cholesterol levels in the oldest-old may be different from those recommended in younger populations, at least in regards to cognitive health.

Preparation of cholesterol oxidase nanoparticles and their application in amperometric determination of cholesterol

The nanoparticle (NP) aggregates of commercial cholesterol oxidase (ChOx) were prepared by desolvation method. The formation and characterization of ChOxNP aggregates were studied by transmission electron microscopy and scanning electron microscopy. NP aggregates were more stable, active and had a higher shelf life than that of free enzyme. An amperometric cholesterol biosensor was constructed by immobilizing ChOxNPs onto Au electrode. The biosensor showed optimum response within 8 s at pH 6.0 and 35 °C, when polarized at +0.27 V versus Ag/AgCl. The biosensor possesses high sensitivity and measures cholesterol concentrations as low as 1.56 mg/dl. The working linear range was 12.5–700 mg/dl for cholesterol. The biosensor was evaluated and employed for measurement of total cholesterol in human serum. The enzyme electrode lost 50 % of its initial activity during its regular use for 180 times over a period of 90 days when stored in 0.1 M sodium phosphate buffer, pH 7.0 at 4 °C.

The effects of phytosterol supplementation on serum LDL-C levels and learning ability in mice fed a high-fat, high-energy diet from gestation onward

A high-fat, high-energy (HFE) diet may be deleterious to the cardiovascular system and mental health. We previously reported that serum cholesterol levels and escape latency were significantly increased in mice by feeding them an HFE diet from gestation onward. In this study, we examined whether an HFE diet supplemented with phytosterols fed to pregnant C57BL/6j dams and their offspring would protect the HFE-diet-induced compromise of the offspring’s learning capability. We measured serum cholesterol levels, brain N-methyl-D-aspartate receptor (NMDAR1) mRNA and protein expression and liver sterol 27-hydroxylase (Cyp27a1) mRNA expression, as well as a Morris water maze performance. The results showed that, compared to mice consuming the HFE diet alone, those also consuming phytosterols (the HFE + PS diet) significantly decreased mean serum low-density lipoprotein cholesterol levels and altered brain NMDAR1 mRNA and protein expression and liver Cyp27a1 mRNA expression. The Morris water maze experiments indicated that dietary phytosterol supplementation slightly decreased the escape latency (p = 0.07). Collectively, these observations suggest that consumption of phytosterols from early in life may help alleviate the detrimental effects of HFE diets in mice.

Lesiones ateroscleróticas tempranas y nivel de colesterol post mortem en un grupo de niños colombianos

Atherosclerosis is an asymptomatic chronic disease, which begins at early age and is difficult to detect during this stage. Prospective studies suggest a causal relationship between total serum cholesterol levels during childhood and early adolescence and the development of cardiovascular diseases in adulthood. The aim of this study was to evaluate the prevalence of early atherosclerotic lesions in the aorta artery of children and its relationship with post-mortem serum cholesterol levels. Post-mortem samples of blood and aorta were taken from 43 subjects aged less than 17 years old. Histopathological analysis (intimal thickening and inflammatory infiltrates) of the thoracic aorta and measurement of total serum cholesterol were performed. The analysis showed thickening of the intima and lymphocyte infiltrates in 93% of children, and macrophage infiltrates in 79.1% of cases. A relationship between the highest terciles of total serum cholesterol levels and the presence of multiple lesions in the aorta wall was found ( P <0.05). This group of children had a high prevalence of early inflammatory atherosclerotic lesions positively related with serum cholesterol levels. To our knowledge this study represents the first report of a relationship between post-mortem total serum cholesterol levels and pathological findings of macrophages and lymphocytes infiltrates in the aorta wall.

P450 Long-term impacts of colectomy surgery among ulcerative colitis patients study (LOCUS): the final analysis

to steroid therapy, although several serious side-effects may limit the use of the drug. Cyclosporine has been reported to increase the total cholesterol level; however the change in the serum cholesterol levels before and after cyclosporine therapy has not been examined in UC patients. The aim of this study was to compare the serum cholesterol levels before and after the cyclosporine therapy in patients with refractory UC and to examine the association between serum cholesterol level and other common side-effects. Methods: We retrospectively assessed the serum cholesterol levels of UC patients who had been treated with cyclosporine. Data of 72 patients (39 female, 33 male, mean age at diagnosis 31.7 years, mean disease duration: 13.5 years) were analyzed statistically. Results: The mean age of UC patients at the start of cyclosporine therapy was 40.3 years, and the mean disease duration at the beginning of the therapy was 8.6 years. The median duration of cyclosporine therapy was 9.6 months, and side effects developed in 52 patients. 65% of them developed increased cholesterol levels. The mean levels of serum cholesterol were 4.48, 6.1 and 5.08mmol/l at the beginning, during and at the end of the therapy. Elevated serum cholesterol levels were detected in 27% of the patients. Serum cholesterol level was significantly increased during and after stopping cyclosporine therapy compared the time before the use of the drug (p < 0.001, p < 0.004). However, cholesterol levels measured during the therapy was significantly higher compared to the time after stopping cyclosporine (p < 0.001). Significant association was found between the increased serum cholesterol levels and side effects developing during cyclosporine therapy. Conclusions: Our findings suggest that cyclosporine therapy may result in increased serum cholesterol levels even in longterm after stopping the therapy. Considering that cholesterol level were significantly more common in patients developing drug-related complications, routine measurement of serum cholesterol can increase the safety of the drug.

P449 Long-term increase of serum cholesterol level in ulcerative colitis patients treated with cyclosporine: an underdiagnosed side effect frequently associated with other drug-related complications

Introduction. Several serious side effects may limit the use of cyclosporine. Cyclosporine has been reported to increase the total cholesterol level; however, the change in serum cholesterol levels before and after cyclosporine therapy has not been examined in ulcerative colitis (UC) patients. The purpose of this article was to compare serum cholesterol levels before and after cyclosporine therapy in patients with refractory UC and to examine the relationship between serum cholesterol levels and other common side effects. Patients and methods. We prospectively assessed serum cholesterol levels in UC patients who had been treated with cyclosporine. Data of 72 patients were analyzed and compared to a control group treated with Infliximab. Results. The average duration of cyclosporine therapy was 9.6 months, and side effects developed in 52 patients. Elevated cholesterol levels were detected in 47.2% of the patients. Serum cholesterol levels were significantly increased during and after discontinuation of cyclosporine therapy compared to the time before use of the drug. However, cholesterol levels measured during cyclosporine therapy were significantly higher compared to the time after its discontinuation (p < 0.001). Patients with drug-related side effects showed higher cholesterol levels after discontinuation of the therapy compared to those who did not experience any adverse events. Conclusions. Our findings suggest that cyclosporine therapy may result in increased serum cholesterol levels even in the long-term, after discontinuation of the therapy. Considering that significantly higher post-therapy cholesterol levels were more common in patients who developed drug-related complications, routine measurement of serum cholesterol may increase the safety of the drug.

Nonalcoholic fatty liver disease and serum lipoproteins: The Multi-Ethnic Study of Atherosclerosis

ObjectiveWhile nonalcoholic fatty liver disease (NAFLD) is associated with the metabolic syndrome, it is not known if NAFLD plays an independent role in the atherogenic dyslipidemia phenotype. Methods and resultsThe Multi-Ethnic Study of Atherosclerosis (MESA) is a population-based prospective cohort study of adults free of clinical cardiovascular disease at enrollment. We tested for a relationship between NAFLD, defined as a liver/spleen (L/S) attenuation ratio of <1 on a non-contrast cardiac CT scan, and multiple measures of fasting serum lipoprotein size, cholesterol and particle concentrations.NAFLD was present in 569 (17%) of 3362 participants. After adjustment for multiple metabolic risk factors, adiposity and measures of insulin resistance (HOMA-IR), NAFLD was independently associated with higher fasting serum triglycerides and lower serum HDL-C. Despite a lack of association with LDL-C, NAFLD was associated with higher LDL particle concentration and lower LDL particle size. Modeling the L/S ratio as a continuous variable, a severity dependent association was observed between atherogenic lipoprotein abnormalities and NAFLD. ConclusionIn a large, multi-ethnic, gender balanced cohort, CT-diagnosed NAFLD was associated with the atherogenic dyslipidemia phenotype in a dose dependent fashion. These relationships persisted after adjustment for several metabolic risk factors and HOMA-IR, suggesting a possible independent pathophysiologic role between NAFLD and dyslipidemia.

Long-term increase in serum cholesterol levels in ulcerative colitis patients treated with cyclosporine: an underdiagnosed side effect frequently associated with other drug-related complications

Introduction. Several serious side effects may limit the use of cyclosporine. Cyclosporine has been reported to increase the total cholesterol level; however, the change in serum cholesterol levels before and after cyclosporine therapy has not been examined in ulcerative colitis (UC) patients. The purpose of this article was to compare serum cholesterol levels before and after cyclosporine therapy in patients with refractory UC and to examine the relationship between serum cholesterol levels and other common side effects. Patients and methods. We prospectively assessed serum cholesterol levels in UC patients who had been treated with cyclosporine. Data of 72 patients were analyzed and compared to a control group treated with Infliximab. Results. The average duration of cyclosporine therapy was 9.6 months, and side effects developed in 52 patients. Elevated cholesterol levels were detected in 47.2% of the patients. Serum cholesterol levels were significantly increased during and after discontinuation of cyclosporine therapy compared to the time before use of the drug. However, cholesterol levels measured during cyclosporine therapy were significantly higher compared to the time after its discontinuation (p < 0.001). Patients with drug-related side effects showed higher cholesterol levels after discontinuation of the therapy compared to those who did not experience any adverse events. Conclusions. Our findings suggest that cyclosporine therapy may result in increased serum cholesterol levels even in the long-term, after discontinuation of the therapy. Considering that significantly higher post-therapy cholesterol levels were more common in patients who developed drug-related complications, routine measurement of serum cholesterol may increase the safety of the drug.

Mild cognitive impairment associates with concurrent decreases in serum cholesterol and cholesterol-related lipoprotein subclasses.

Accumulating evidence suggests that serum lipids are associated with cognitive decline and dementias. However, majority of the existing information concerns only serum total cholesterol (TC) and data at the level of lipoprotein fractions and subclasses is limited. The aim of this study was to explore the levels and trends of main cholesterol and triglyceride measures and eight lipoprotein subclasses during normal aging and the development of mild cognitive impairment by following a group of elderly for six years. Longitudinal. City of Kuopio, Finland. 45 elderly individuals of which 20 developed mild cognitive impairment (MCI) during the follow-up. On each visit participants underwent an extensive neuropsychological and clinical assessment. Lipoprotein levels were measured via 1H NMR from native serum samples. Serum cholesterol and many primarily cholesterol-associated lipoprotein measures clearly decreased in MCI while the trends were increasing for those elderly people who maintained normal cognition. These findings suggest that a decreasing trend in serum cholesterol measures in elderly individuals may suffice as an indication for more detailed inspection for potential signs of cognitive decline.

Mitochondrial DNA Variant for Complex I Reveals a Role in Diabetic Cardiac Remodeling

Myocardial remodeling and dysfunction are serious complications of type 2 diabetes mellitus (T2DM). Factors controlling their development are not well established. To specifically address the role of the mitochondrial genome, we developed novel conplastic rat strains, i.e. strains with the same nuclear genome but a different mitochondrial genome. The new animals were named T2DN(mtFHH) and T2DN(mtWistar), where the acronym T2DN denotes their common nuclear genome (type 2 diabetic nephropathy (T2DN) rats) and mtFHH or mtWistar the origin of their mitochondria, Fawn Hooded Hypertensive (FHH) or Wistar rats, respectively. The T2DN(mtFHH) and T2DN(mtWistar) showed a similar progression of diabetes as determined by HbA1c, cholesterol, and triglycerides with normal blood pressure, thus enabling investigation of the specific role of the mitochondrial genome in cardiac function without the confounding effects of obesity or hypertension found in other models of diabetes. Echocardiographic analysis of 12-week-old animals showed no abnormalities, but at 12 months of age the T2DN(mtFHH) showed left ventricular remodeling that was verified by histology. Decreased complex I and complex IV but not complex II activity within the electron transport chain was found only in T2DN(mtFHH), which was not explained by differences in protein content. Decreased cardiac ATP levels in T2DN(mtFHH) were in agreement with a lower ATP synthetic capacity by isolated mitochondria. Together, our data provide experimental evidence that mtDNA sequence variations have an additional role in energetic heart deficiency. The mitochondrial DNA background may explain the increased susceptibility of certain T2DM patients to develop myocardial dysfunction.

Parenteral Plant Sterols and Intestinal Failure–associated Liver Disease in Neonates

We prospectively evaluated incidence of prolonged (>28 days) parenteral nutrition (PN), associated complications, and significance of parenteral plant sterols (PS) in neonatal intestinal failure-associated liver disease (IFALD) compared with children. We recruited 28 neonates (mean age 50 days, range 28-126) and 11 children (6.9 y, 2.1-16.6) in all of Finland. Patients underwent repeated measurements of serum cholesterol, noncholesterol sterols, including PS, cholestanol and cholesterol precursors, and liver biochemistry during and 1 month after discontinuation of PN. Healthy matched neonates (n=10) and children (n=22) served as controls. IFALD occurred more frequently among neonates (63%) than children (27%; P<0.05). Ratios of serum PS, including stigmasterol, sitosterol, avenasterol, and campesterol, and total PS were increased among neonates compared with healthy controls and children on PN by 2- to 22- and 2- to 5-fold (P<0.005), respectively. Neonates with IFALD had significantly higher ratios of serum PS and cholestanol compared with neonates without IFALD (P<0.05). Total duration of PN associated with serum cholestanol, stigmasterol, avenasterol, alanine aminotransferase, and aspartate aminotransferase (r=0.472-0.636, P<0.05). Cholestanol and individual serum PS, excluding campesterol, reflected direct bilirubin (r=0.529-0.688, P<0.05). IFALD persisted after discontinuation of PN in 25% of neonates with 4.2- and 2.2-times higher ratios of serum stigmasterol and cholestanol compared with neonates without IFALD (P<0.05). Frequent occurrence of IFALD among neonates on PN displays an association to duration of PN and markedly increased serum PS, especially stigmasterol, in comparison to healthy neonates and children on PN. Striking accumulation of parenteral PS may contribute to IFALD among neonates.

Next stop for HDL: the lung

Next stop for <scp>HDL</scp>: the lung

Diet and exercise in an obese mouse fed a high-fat diet improve metabolic health and reverse perturbed sperm function

Male obesity is associated with reduced sperm motility and morphology and increased sperm DNA damage and oxidative stress; however, the reversibility of these phenotypes has never been studied. Therefore, the aim of this study was to assess the reversibility of obesity and its associated sperm physiology and function in mice in response to weight loss through diet and exercise. C57BL6 male mice (n = 40) were fed either a control diet (CD; 6% fat) or a high-fat diet (HFD; 21% fat) for 10 wk before allocation to either diet and/or swimming exercise interventions for 8 wk. Diet alone reduced adiposity (1.6-fold) and serum cholesterol levels (1.7-fold, P < 0.05), while exercise alone did not alter these, but exercise plus diet also improved glucose tolerance (1.3-fold, P < 0.05). Diet and/or exercise improved sperm motility (1.2-fold) and morphology (1.1-fold, P < 0.05), and reduced sperm DNA damage (1.5-fold), reactive oxygen species (1.1-fold), and mitochondrial membrane potential (1.2-fold, P < 0.05) and increased sperm binding (1.4-fold) (P < 0.05). Sperm parameters were highly correlated with measures of glycemia, insulin action, and serum cholesterol (all P < 0.05) regardless of adiposity or intervention, suggesting a link between systemic metabolic status and sperm function. This is the first study to show that the abnormal sperm physiology resulting from obesity can be reversed through diet and exercise, even in the presence of ongoing obesity, suggesting that diet and lifestyle interventions could be a combined approach to target subfertility in overweight and obese men.