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Hormones (Athens, Greece) Dec 2023Hypercholesterolemia due to a high-cholesterol diet is linked to numerous diseases and may lead to male infertility. However, the underlying mechanism remains unknown....
PURPOSE
Hypercholesterolemia due to a high-cholesterol diet is linked to numerous diseases and may lead to male infertility. However, the underlying mechanism remains unknown. The maintenance of male fertility requires intact testicular structures (including seminiferous tubules and mesenchyme) and functioning cells (Leydig cells, Sertoli cells and germ cells, etc.), production of appropriate concentrations of sex hormones, and cooperation among testicular cells. Thus, we considered whether male fertility declined as the structure and function of testicular cells were altered in rats on a high-cholesterol diet.
METHODS
Male Sprague Dawley rats were fed either a standard or a high-cholesterol diet for 16 weeks. Serum sex hormones, lipid components, semen quality, and fertility rate were assayed in the rats. The 3β-hydroxysteroid dehydrogenase (3β-HSD), Wilms tumor 1 (WT-1), and deleted in azoospermia-like (DAZL) were regarded as specific markers of Leydig, Sertoli, and germ cells in rats. In addition, the ultrastructure of the testis and expression levels of particular marker molecules of testicular cells were further investigated.
RESULTS
Compared to rats fed on a regular diet, the serum testosterone levels and sperm progressive motility decreased in rats fed high cholesterol. Moreover, we observed a deformed nucleus, dilated smooth endoplasmic reticulum, and swollen mitochondria of Leydig cells and a schizolytic nucleus of Sertoli cells in rats on a high-cholesterol diet. The 3β-HSD, WT-1, and DAZL protein expression levels were significantly reduced in rats on a high-cholesterol diet.
CONCLUSIONS
Our results showed that a high-cholesterol diet adversely affected testosterone production and sperm progressive motility, possibly due to Leydig, Sertoli, and germ cell abnormalities.
Topics: Humans; Male; Rats; Animals; Hypercholesterolemia; Semen Analysis; Rats, Sprague-Dawley; Semen; Testis; Leydig Cells; Testosterone; Testicular Diseases; Diet; Cholesterol
PubMed: 37596375
DOI: 10.1007/s42000-023-00472-4 -
Frontiers in Endocrinology 2023Fasting morning cortisol (FMC) stress hormone levels, are suggested to reflect increased cardiometabolic risk. Acute response to weight loss diet could elevate FMC.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Fasting morning cortisol (FMC) stress hormone levels, are suggested to reflect increased cardiometabolic risk. Acute response to weight loss diet could elevate FMC. Richer Polyphenols and lower carbohydrates diets could favor FMC levels. We aimed to explore the effect of long-term high polyphenol Mediterranean diet (green-MED) on FMC and its relation to metabolic health.
METHODS
We randomized 294 participants into one of three dietary interventions for 18-months: healthy dietary guidelines (HDG), Mediterranean (MED) diet, and Green-MED diet. Both MED diets were similarly hypocaloric and lower in carbohydrates and included walnuts (28 g/day). The high-polyphenols/low-meat Green-MED group further included green tea (3-4 cups/day) and a Wolffia-globosa Mankai plant 1-cup green shakeFMC was obtained between 07:00-07:30AM at baseline, six, and eighteen-months.
RESULTS
Participants (age=51.1years, 88% men) had a mean BMI of 31.3kg/m, FMC=304.07nmol\L, and glycated-hemoglobin-A1c (HbA1c)=5.5%; 11% had type 2 diabetes and 38% were prediabetes. Baseline FMC was higher among men (308.6 ± 90.05nmol\L) than women (269.6± 83.9nmol\L;p=0.02). Higher baseline FMC was directly associated with age, dysglycemia, MRI-assessed visceral adiposity, fasting plasma glucose (FPG), high-sensitivity C-reactive-protein (hsCRP), testosterone, Progesterone and TSH levels (p ≤ 0.05 for all). The 18-month retention was 89%. After 6 months, there were no significant changes in FMC among all intervention groups. However, after 18-months, both MED groups significantly reduced FMC (MED=-1.6%[-21.45 nmol/L]; Green-MED=-1.8%[-26.67 nmol/L]; p<0.05 vs. baseline), as opposed to HDG dieters (+4%[-12 nmol/L], p=0.28 vs. baseline), whereas Green-MED diet FMC change was significant as compared to HDG diet group (p=0.048 multivariable models). Overall, 18-month decrease in FMC levels was associated with favorable changes in FPG, HbA1c, hsCRP, TSH, testosterone and MRI-assessed hepatosteatosis, and with unfavorable changes of HDLc (p<0.05 for all, weight loss adjusted, multivariable models).
CONCLUSION
Long-term adherence to MED diets, and mainly green-MED/high polyphenols diet, may lower FMC, stress hormone, levels,. Lifestyle-induced FMC decrease may have potential benefits related to cardiometabolic health, irrespective of weight loss.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier NCT03020186.
Topics: Female; Humans; Male; Middle Aged; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet, Mediterranean; Fasting; Glycated Hemoglobin; Hydrocortisone; Testosterone; Thyrotropin; Weight Loss
PubMed: 38034010
DOI: 10.3389/fendo.2023.1243910 -
Biomedicine & Pharmacotherapy =... Dec 2023Nuclear receptors (NRs) represent intracellular proteins that function as a signaling network of transcriptional factors to control genes in response to a variety of... (Review)
Review
Nuclear receptors (NRs) represent intracellular proteins that function as a signaling network of transcriptional factors to control genes in response to a variety of environmental, dietary, and hormonal stimulations or serve as orphan receptors lacking a recognized ligand. They also play an essential role in normal development, metabolism, cell growth, cell division, physiology, reproduction, and homeostasis and function as biological markers for tumor subclassification and as targets for hormone therapy. NRs, including steroid hormone receptors (SHRs), have been studied as tools to examine the fundamentals of transcriptional regulation within the development of mammals and human physiology, in addition to their links to disturbances. In this regard, it is widely recognized that aberrant NR signaling is responsible for the pathological growth of hormone-dependent tumors in response to SHRs dysregulation and consequently represents a potential therapeutic candidate in a range of diseases, as in the case of prostate cancer and breast cancer. On the other hand, phytosterols are a group of plant-derived compounds that act directly as ligands for NRs and have proven their efficacy in the management of diabetes, heart diseases, and cancers. However, these plants are not suggested in cases of hormone-dependent cancer since a certain group of plants contains molecules with a chemical structure similar to that of estrogens, which are known as phytoestrogens or estrogen-like compounds, such as lignans, coumestans, and isoflavones. Therefore, it remains an open and controversial debate regarding whether consuming a phytosterol-rich diet and adopting a vegetarian lifestyle like the Mediterranean diet may increase the risk of developing steroid hormone-dependent cancers by constitutively activating SHRs and thereby leading to tumor transformation. Overall, the purpose of this review is to better understand the relevant mechanistic pathways and explore epidemiological investigations in order to establish that phytosterols may contribute to the activation of NRs as cancer drivers in hormone-dependent cancers.
Topics: Animals; Humans; Male; Breast Neoplasms; Estrogens; Mammals; Phytoestrogens; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid; Steroids; Phytosterols
PubMed: 37944439
DOI: 10.1016/j.biopha.2023.115783 -
The Journal of Nutrition Oct 2023Most pregnant women in the United States are at risk of inadequate intake of vitamin A, vitamin D, folic acid, calcium, iron, and omega-3 fatty acids from foods alone....
BACKGROUND
Most pregnant women in the United States are at risk of inadequate intake of vitamin A, vitamin D, folic acid, calcium, iron, and omega-3 fatty acids from foods alone. Very few United States dietary supplements provide sufficient doses of all 6 nutrients without inducing excess intake.
OBJECTIVE
We aimed to identify energy-efficient foods that provide sufficient doses of these nutrients and could be consumed in lieu of dietary supplements to achieve the recommended intake in pregnancy.
METHODS
In a previous analysis of 2,450 pregnant women, we calculated the range of additional intake needed to shift 90% of participants to intake above the estimated average requirement and keep 90% below the tolerable upper level for these 6 nutrients. Here, we identified foods and beverages from the 2019 to 2020 Food and Nutrient Database for Dietary Studies that provide target levels of these nutrients without exceeding the additional energy intake recommended for pregnancy beginning in the second trimester (340 kilocalories).
RESULTS
We identified 2358 candidate foods meeting the target intake range for at least one nutrient. No candidate foods provided target amounts of all 6 nutrients. Seaweed (raw or cooked without fat) provided sufficient vitamin A, folate, calcium, iron, and omega-3s (5 of 6 nutrients) but would require an intake of >5 cups/d. Twenty-one other foods/beverages (mainly fish, vegetables, and beverages) provided target amounts of 4 of the 6 nutrients. Few foods met targets for vitamin D (n = 54) or iron (n = 93).
CONCLUSIONS
Results highlight the difficulty in meeting nutritional requirements from diet alone and imply that dietary supplements are likely necessary to meet vitamin D and iron targets in pregnancy, as well as omega-3 fatty acid targets for individuals who do not consume fish products. Other foods could be added in limited amounts to help meet intake targets without exceeding caloric recommendations or nutrient safety limits.
Topics: Animals; Female; Humans; Pregnancy; United States; Micronutrients; Vitamin A; Calcium; Diet; Dietary Supplements; Vitamins; Folic Acid; Vegetables; Vitamin D; Iron
PubMed: 37604382
DOI: 10.1016/j.tjnut.2023.08.012 -
Redox Biology Aug 2023To identify metabolomic reprogramming in early hyperlipidemia, unbiased metabolome was screened in four tissues from ApoE mice fed with high fat diet (HFD) for 3 weeks....
To identify metabolomic reprogramming in early hyperlipidemia, unbiased metabolome was screened in four tissues from ApoE mice fed with high fat diet (HFD) for 3 weeks. 30, 122, 67, and 97 metabolites in the aorta, heart, liver, and plasma, respectively, were upregulated. 9 upregulated metabolites were uremic toxins, and 13 metabolites, including palmitate, promoted a trained immunity with increased syntheses of acetyl-CoA and cholesterol, increased S-adenosylhomocysteine (SAH) and hypomethylation and decreased glycolysis. The cross-omics analysis found upregulation of 11 metabolite synthetases in ApoE aorta, which promote ROS, cholesterol biosynthesis, and inflammation. Statistical correlation of 12 upregulated metabolites with 37 gene upregulations in ApoE aorta indicated 9 upregulated new metabolites to be proatherogenic. Antioxidant transcription factor NRF2-/- transcriptome analysis indicated that NRF2 suppresses trained immunity-metabolomic reprogramming. Our results have provided novel insights on metabolomic reprogramming in multiple tissues in early hyperlipidemia oriented toward three co-existed new types of trained immunity.
Topics: Mice; Animals; Hyperlipidemias; Acetyl Coenzyme A; S-Adenosylhomocysteine; NF-E2-Related Factor 2; Cholesterol; Diet, High-Fat; Apolipoproteins E; Glycolysis
PubMed: 37364513
DOI: 10.1016/j.redox.2023.102771 -
Advances in Food and Nutrition Research 2024Celiac disease (CD) is an immune-mediated condition affecting the small intestine. Its reported global prevalence falls within the range of 0.7% to 1.4%. Notably,... (Review)
Review
Celiac disease (CD) is an immune-mediated condition affecting the small intestine. Its reported global prevalence falls within the range of 0.7% to 1.4%. Notably, historically, higher rates, reaching 1% in Western Ireland, have been documented. Recent research has even revealed prevalence rates as elevated as 2% in northern Europe. These findings underscore the urgency for swift and cost-effective diagnosis, especially in individuals identified through screening efforts. At present, the diagnosis of CD relies on a multifaceted approach involving positive serological markers such as IgA anti-tissue transglutaminase (anti-TTG) and anti-endomysial antibodies (anti-EMA). These serological findings are assessed in conjunction with classical histological alterations, as outlined in the Marsh classification. CD is an inflammatory condition triggered by the consumption of gluten, resulting from intricate interactions between genetic, immunological, and environmental factors. CD is linked to malabsorption, leading to nutritional deficiencies. Individuals with CD are required to adhere to a gluten-free diet, which itself can lead to nutrient deficiencies. One such deficiency includes vitamin D, and there is substantial experimental evidence supporting the notion of a bidirectional relationship between CD and vitamin D status. A low level of vitamin D has a detrimental impact on the clinical course of the disease. Here we summarize the key characteristics of CD and explore the prominent roles of vitamin D in individuals with CD.
Topics: Celiac Disease; Humans; Vitamin D; Vitamin D Deficiency; Diet, Gluten-Free
PubMed: 38777415
DOI: 10.1016/bs.afnr.2023.12.004 -
Nature Communications Oct 2023Identifying oncological applications for drugs that are already approved for other medical indications is considered a possible solution for the increasing costs of...
Identifying oncological applications for drugs that are already approved for other medical indications is considered a possible solution for the increasing costs of cancer treatment. Under the hypothesis that nutritional stress through fasting might enhance the antitumour properties of at least some non-oncological agents, by screening drug libraries, we find that cholesterol biosynthesis inhibitors (CBIs), including simvastatin, have increased activity against cancers of different histology under fasting conditions. We show fasting's ability to increase CBIs' antitumour effects to depend on the reduction in circulating insulin, insulin-like growth factor-1 and leptin, which blunts the expression of enzymes from the cholesterol biosynthesis pathway and enhances cholesterol efflux from cancer cells. Ultimately, low cholesterol levels through combined fasting and CBIs reduce AKT and STAT3 activity, oxidative phosphorylation and energy stores in the tumour. Our results support further studies of CBIs in combination with fasting-based dietary regimens in cancer treatment and highlight the value of fasting for drug repurposing in oncology.
Topics: Simvastatin; Fasting; Diet; Insulin; Cholesterol
PubMed: 37907500
DOI: 10.1038/s41467-023-42652-1 -
Journal of Public Health (Oxford,... Nov 2023Previous studies of the UK Biobank have examined intake of single food items and their association with health outcomes. Our aim was to develop a dietary quality score...
BACKGROUND
Previous studies of the UK Biobank have examined intake of single food items and their association with health outcomes. Our aim was to develop a dietary quality score and examine the relationship between this score and markers of cardiometabolic health.
METHODS
Principal component analysis was performed on dietary data from UK Biobank participants. Linear regression was used to analyse the relationship between diet and cardiometabolic health.
RESULTS
The first component explained 14% of the variation in the dietary data. It was characterised by high consumption of meat and low fibre carbohydrates, and a low intake of fruit and vegetables. A higher score, indicative of healthier diet, was associated with lower systolic and diastolic blood pressure (β -0.81, 95% CI -1.0, -0.62; β - .61, 95% CI -0.72, -0.5) and a healthier lipid profile (lower levels of cholesterol β -0.05, 95% CI -0.06, -0.04, triglycerides β -0.05, 95% CI -0.06, -0.03, and higher HDL cholesterol β 0.01, 95% CI 0, 0.01).
CONCLUSIONS
The dietary quality score was a good approximation of overall dietary quality. An unhealthy diet was associated with markers of poorer cardiometabolic health.
Topics: Humans; Biological Specimen Banks; Diet; Cholesterol; Cardiovascular Diseases; United Kingdom
PubMed: 37385972
DOI: 10.1093/pubmed/fdad103 -
The American Journal of Clinical... May 2024Distinct circulating bile acid (BA) subtypes may play roles in regulating lipid homeostasis and atherosclerosis. (Randomized Controlled Trial)
Randomized Controlled Trial
Changes in bile acid subtypes and improvements in lipid metabolism and atherosclerotic cardiovascular disease risk: the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial.
BACKGROUND
Distinct circulating bile acid (BA) subtypes may play roles in regulating lipid homeostasis and atherosclerosis.
OBJECTIVES
We investigated whether changes in circulating BA subtypes induced by weight-loss dietary interventions were associated with improved lipid profiles and atherosclerotic cardiovascular disease (ASCVD) risk estimates.
METHODS
This study included adults with overweight or obesity (n = 536) who participated in a randomized weight-loss dietary intervention trial. Circulating primary and secondary unconjugated BAs and their taurine-/glycine-conjugates were measured at baseline and 6 mo after the weight-loss diet intervention. The ASCVD risk estimates were calculated using the validated equations.
RESULTS
At baseline, higher concentrations of specific BA subtypes were related to higher concentrations of atherogenic very low-density lipoprotein lipid subtypes and ASCVD risk estimates. Weight-loss diet-induced decreases in primary BAs were related to larger reductions in triglycerides and total cholesterol [every 1 standard deviation (SD) decrease of glycocholate, glycochenodeoxycholate, or taurochenodeoxycholate was related to β (standard error) -3.3 (1.3), -3.4 (1.3), or -3.8 (1.3) mg/dL, respectively; P < 0.05 for all]. Greater decreases in specific secondary BA subtypes were also associated with improved lipid metabolism at 6 mo; there was β -4.0 (1.1) mg/dL per 1-SD decrease of glycoursodeoxycholate (P =0.003) for changes in low-density lipoprotein cholesterol. We found significant interactions (P-interaction < 0.05) between dietary fat intake and changes in BA subtypes on changes in ASCVD risk estimates; decreases in primary and secondary BAs (such as conjugated cholate or deoxycholate) were significantly associated with improved ASCVD risk after consuming a high-fat diet, but not after consuming a low-fat diet.
CONCLUSIONS
Decreases in distinct BA subtypes were associated with improved lipid profiles and ASCVD risk estimates, highlighting the importance of changes in circulating BA subtypes as significant factors linked to improved lipid metabolism and ASCVD risk estimates in response to weight-loss dietary interventions. Habitual dietary fat intake may modify the associations of changes in BAs with ASCVD risk. This trial was registered at clinicaltrials.gov as NCT00072995.
Topics: Humans; Bile Acids and Salts; Male; Female; Middle Aged; Overweight; Lipid Metabolism; Atherosclerosis; Adult; Diet, Reducing; Risk Factors; Obesity; Weight Loss; Aged; Cardiovascular Diseases
PubMed: 38428740
DOI: 10.1016/j.ajcnut.2024.02.019 -
Journal of the American Nutrition... Aug 2023Cardiometabolic diseases and metabolic syndrome (MetS) are becoming increasingly prevalent in low- and middle-income countries (LMICs). Cardiometabolic diseases and MetS...
BACKGROUND
Cardiometabolic diseases and metabolic syndrome (MetS) are becoming increasingly prevalent in low- and middle-income countries (LMICs). Cardiometabolic diseases and MetS are closely associated with low-grade systemic inflammation, which may be modified by diet. Previous studies have focused on the association of dietary inflammation with MetS and cardiometabolic risk in adult populations, but few studies have examined this issue in children, especially in LMICs.
METHODS
We conducted a cross-sectional study to explore the association of dietary inflammation with cardiometabolic risk components and MetS in urban Ecuadorian children aged 6-12 years old (n = 276). A semi-quantitative food frequency questionnaire (FFQ) was used to collect data on child dietary intake. Dietary inflammation was evaluated using an energy-adjusted Dietary Inflammatory Index (DII), divided into quartiles. Data were also collected on cardiometabolic risk indicators including blood lipids, blood pressure (BP), blood glucose, body mass index, and waist circumference. Data were analyzed using multivariable linear and logistic regression.
RESULTS
Child DII scores ranged from -4.87 (most anti-inflammatory) to 4.75 (most pro-inflammatory). We transformed the continuous scores into quartiles (Q): Q1 was the most anti-inflammatory (-4.87 to -3.35), Q2 was anti-inflammatory (-3.34 to -1.45), Q3 was pro-inflammatory (-1.44 to 1.08), and Q4 was the most pro-inflammatory (1.09 to 4.75). In the covariate-adjusted model, DII scores were positively associated with total blood cholesterol (p = 0.027), triglycerides (p = 0.034), and diastolic BP (p = 0.013). In addition, for every one-unit increase in DII score, MetS increased by 1.20 in the covariate-adjusted model (95% CI = 1.01,1.43).
CONCLUSIONS
The findings suggest that more pro-inflammatory diets may contribute to poorer cardiometabolic health in school-age children. This is important because even small increases in child blood pressure, blood cholesterol, and glucose levels over time can damage health and lead to earlier progression to conditions such as hypertension and atherosclerosis.
Topics: Adult; Humans; Child; Cross-Sectional Studies; Ecuador; Diet; Metabolic Syndrome; Inflammation; Cholesterol; Cardiovascular Diseases
PubMed: 35980812
DOI: 10.1080/27697061.2022.2113177