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1.
Sci Rep ; 14(1): 10353, 2024 05 06.
Article in English | MEDLINE | ID: mdl-38710742

ABSTRACT

This study was conducted to verify the essentiality of dietary cholesterol for early juvenile slipper lobster, Thenus australiensis (initial weight 4.50 ± 0.72 g, mean ± SD, CV = 0.16), and to explore the potential for interactions between dietary cholesterol and phospholipid. An 8-week experiment was conducted using six experimental feeds containing three supplemental cholesterol concentrations (0, 0.2 and 0.4% dry matter) at two supplemental phospholipid concentrations (0% and 1.0% dry matter). Dietary cholesterol concentrations of ≥ 0.2% resulted in up to threefold greater weight gain compared to 0% dietary cholesterol, but without any significant main or interactive dietary phospholipid effect. An interaction was observed for lobster survival with lowest survival (46%) recorded for combined 0% cholesterol and 0% phospholipid compared to every other treatment (71-100%). However, all surviving lobsters at 0% dietary cholesterol, regardless of dietary phospholipid level, were in poor nutritional condition. Apparent feed intake (AFI) was significantly higher at dietary cholesterol ≥ 0.2% but was lower for each corresponding dietary cholesterol level at 1% dietary phospholipid. This implied that the feed conversion ratio was improved with supplemental phospholipid. In conclusion, this study confirms the essential nature of dietary cholesterol and that dietary phospholipid can provide additional benefits.


Subject(s)
Animal Feed , Cholesterol, Dietary , Palinuridae , Phospholipids , Animals , Phospholipids/metabolism , Cholesterol, Dietary/metabolism , Palinuridae/metabolism , Animal Feed/analysis , Animal Nutritional Physiological Phenomena
2.
Hepatol Commun ; 8(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38696365

ABSTRACT

Cholesterol is an essential lipid molecule in mammalian cells. It is not only involved in the formation of cell membranes but also serves as a raw material for the synthesis of bile acids, vitamin D, and steroid hormones. Additionally, it acts as a covalent modifier of proteins and plays a crucial role in numerous life processes. Generally, the metabolic processes of cholesterol absorption, synthesis, conversion, and efflux are strictly regulated. Excessive accumulation of cholesterol in the body is a risk factor for metabolic diseases such as cardiovascular disease, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). In this review, we first provide an overview of the discovery of cholesterol and the fundamental process of cholesterol metabolism. We then summarize the relationship between dietary cholesterol intake and the risk of developing MASLD, and also the animal models of MASLD specifically established with a cholesterol-containing diet. In the end, the role of cholesterol-induced inflammation in the initiation and development of MASLD is discussed.


Subject(s)
Cholesterol, Dietary , Cholesterol , Humans , Cholesterol/metabolism , Animals , Cholesterol, Dietary/adverse effects , Fatty Liver/metabolism , Inflammation/metabolism , Disease Models, Animal , Lipid Metabolism
3.
Int J Mol Sci ; 25(10)2024 May 15.
Article in English | MEDLINE | ID: mdl-38791421

ABSTRACT

Adequate experimental animal models play an important role in an objective assessment of the effectiveness of medicines and functional foods enriched with biologically active substances. The aim of our study was a comparative assessment of the effect of consumption of 1 or 2% cholesterol with and without regular (two times a week), moderate running exercise on the main biomarkers of lipid and cholesterol metabolism, as well as the intestinal microbiota of male Wistar rats. In experimental rats, a response of 39 indicators (body weight, food consumption, serum biomarkers, liver composition, and changes in intestinal microbiota) was revealed. Total serum cholesterol level increased 1.8 times in animals consuming cholesterol with a simultaneous increase in low-density lipoprotein cholesterol (2 times) and decrease in high-density lipoprotein cholesterol (1.3 times) levels compared to the control animals. These animals had 1.3 times increased liver weight, almost 5 times increased triglycerides level, and more than 6 times increased cholesterol content. There was a tendency towards a decrease in triglycerides levels against the background of running exercise. The consumption of cholesterol led to a predominance of the Bacteroides family, due to a decrease in F. prausnitzii (1.2 times) and bifidobacteria (1.3 times), as well as an increase in Escherichia family (1.2 times). The running exercise did not lead to the complete normalization of microbiota.


Subject(s)
Gastrointestinal Microbiome , Lipid Metabolism , Physical Conditioning, Animal , Rats, Wistar , Animals , Male , Gastrointestinal Microbiome/drug effects , Lipid Metabolism/drug effects , Rats , Liver/metabolism , Cholesterol/blood , Cholesterol, Dietary , Triglycerides/blood , Biomarkers/blood , Body Weight , Diet, High-Fat/adverse effects
4.
Biochem Biophys Res Commun ; 719: 150088, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-38740003

ABSTRACT

Berberine (BBR) is a traditional Chinese herb with broad antimicrobial activity. Gut microbiota plays an important role in the metabolism of bile acids and cholesterol. Our study investigated the effects of BBR on alleviating cholesterol and bile acid metabolism disorders induced by high cholesterol diet in mice. Adult male C57BL/6J mice fed with high cholesterol diet (HC) containing 1.25 % cholesterol (HC group) or fed with chow diet containing 0.02 % cholesterol (Chow group) served as controls. BBR50 and BBR100 group mice were fed with HC, and oral BBR daily at doses of 50 or 100 mg/kg respectively for 8 weeks. The results showed that BBR could reshape the homeostasis and composition of gut microbiota. The abundance of Clostridium genera was significantly inhibited by BBR, which resulted in a significant reduction of secondary bile acids within the enterohepatic circulation and a significant lower hydrophobic index of bile acids. The absorption of cholesterol in intestine, the deposition of cholesterol in liver and the excretion of cholesterol in biliary tract were significantly inhibited by BBR, which promoted the unsaturation of cholesterol in bile. These findings suggest the potential utility of BBR as a functional food to alleviate the negative effects of high cholesterol diet.


Subject(s)
Berberine , Bile Acids and Salts , Cholesterol, Dietary , Cholesterol , Gastrointestinal Microbiome , Mice, Inbred C57BL , Animals , Berberine/pharmacology , Bile Acids and Salts/metabolism , Male , Cholesterol/metabolism , Mice , Gastrointestinal Microbiome/drug effects , Cholesterol, Dietary/adverse effects , Cholesterol, Dietary/metabolism , Diet, High-Fat/adverse effects , Liver/metabolism , Liver/drug effects
5.
Fish Shellfish Immunol ; 150: 109621, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38740230

ABSTRACT

This study aims to explore the effects of supplementing cholesterol in plant-based feed on intestinal barriers (including physical barrier, chemical barrier, immune barrier, biological barrier) of GIFT strain tilapia (Oreochromis niloticus). Four isonitrogenous and isolipidic diets were prepared as follows: plant-based protein diet (Con group) containing corn protein powder, soybean meal, cottonseed meal, and rapeseed meal, with the addition of cholesterol at a level of 0.6 % (C0.6 % group), 1.2 % (C1.2 % group), and 1.8 % (C1.8 % group), respectively. A total of 360 fish (mean initial weight of (6.08 ± 0.12) g) were divided into 12 tanks with 30 fish per tank, each treatment was set with three tanks and the feeding period lasted 9 weeks. Histological analysis revealed that both the C0.6 % and C1.2 % groups exhibited a more organized intestinal structure, with significantly increased muscle layer thickness compared to the Con group (P < 0.05). Furthermore, in the C1.2 % group, there was a significant up-regulation of tight junction-related genes (claudin-14, occludin, zo-1) compared to the Con group (P < 0.05). 5-ethynyl-2'-deoxyuridine staining results also demonstrated a notable enhancement in intestinal cell proliferation within the C1.2 % group (P < 0.05). Regarding the intestinal chemical barrier, trypsin and lipase activities were significantly elevated in the C1.2 % group (P < 0.05), while hepcidin gene expression was considerably down-regulated in this group but up-regulated in the C1.8 % group (P < 0.05). In terms of the intestinal immune barrier, inflammation-related gene expression levels (tnf-α, il-1ß, caspase 9, ire1, perk, atf6) were markedly reduced in the C1.2 % group (P < 0.05). Regarding the intestinal biological barrier, the composition of the intestinal microbiota indicated that compared to the Con group, both the 0.6 % and 1.2 % groups showed a significant increase in Shannon index (P < 0.05). Additionally, there was a significant increase in the abundance of Firmicutes and Clostridium in the C1.2 % group (P < 0.05). In summary, supplementation of 1.2 % cholesterol in the plant-based diet exhibits the potential to enhance intestinal tight junction function and improve the composition of intestinal microbiota, thereby significantly promoting tilapia's intestinal health.


Subject(s)
Animal Feed , Cichlids , Diet , Intestines , Animals , Cichlids/immunology , Animal Feed/analysis , Diet/veterinary , Intestines/drug effects , Intestines/immunology , Cholesterol, Dietary/administration & dosage , Cholesterol, Dietary/adverse effects , Fish Diseases/immunology , Dietary Supplements/analysis , Random Allocation , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Diet, Plant-Based
6.
Diabetes Care ; 47(6): 1092-1098, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38593324

ABSTRACT

OBJECTIVE: Whether genetic susceptibility to disease and dietary cholesterol (DC) absorption contribute to inconsistent associations of DC consumption with diabetes and cardiovascular disease (CVD) remains unclear. RESEARCH DESIGN AND METHODS: DC consumption was assessed by repeated 24-h dietary recalls in the UK Biobank. A polygenetic risk score (PRS) for DC absorption was constructed using genetic variants in the Niemann-Pick C1-Like 1 and ATP Binding Cassettes G5 and G8 genes. PRSs for diabetes, coronary artery disease, and stroke were also created. The associations of DC consumption with incident diabetes (n = 96,826) and CVD (n = 94,536) in the overall sample and by PRS subgroups were evaluated using adjusted Cox models. RESULTS: Each additional 300 mg/day of DC consumption was associated with incident diabetes (hazard ratio [HR], 1.17 [95% CI, 1.07-1.27]) and CVD (HR, 1.09 [95% CI, 1.03-1.17]), but further adjusting for BMI nullified these associations (HR for diabetes, 0.99 [95% CI, 0.90-1.09]; HR for CVD, 1.04 [95% CI, 0.98-1.12]). Genetic susceptibility to the diseases did not modify these associations (P for interaction ≥0.06). The DC-CVD association appeared to be stronger in people with greater genetic susceptibility to cholesterol absorption assessed by the non-high-density lipoprotein cholesterol-related PRS (P for interaction = 0.04), but the stratum-level association estimates were not statistically significant. CONCLUSIONS: DC consumption was not associated with incident diabetes and CVD, after adjusting for BMI, in the overall sample and in subgroups stratified by genetic predisposition to cholesterol absorption and the diseases. Nevertheless, whether genetic predisposition to cholesterol absorption modifies the DC-CVD association requires further investigation.


Subject(s)
Cardiovascular Diseases , Cholesterol, Dietary , Humans , Male , Female , Cardiovascular Diseases/genetics , Cardiovascular Diseases/epidemiology , Middle Aged , Cholesterol, Dietary/adverse effects , Cholesterol, Dietary/administration & dosage , Diabetes Mellitus/genetics , Diabetes Mellitus/epidemiology , Aged , Adult , Genetic Predisposition to Disease , ATP Binding Cassette Transporter, Subfamily G, Member 8/genetics , Membrane Transport Proteins/genetics , ATP Binding Cassette Transporter, Subfamily G, Member 5/genetics
7.
Sci Rep ; 14(1): 9471, 2024 04 24.
Article in English | MEDLINE | ID: mdl-38658568

ABSTRACT

Most metastases in breast cancer occur via the dissemination of tumor cells through the bloodstream. How tumor cells enter the blood (intravasation) is, however, a poorly understood mechanism at the cellular and molecular levels. Particularly uncharacterized is how intravasation is affected by systemic nutrients. High levels of systemic LDL-cholesterol have been shown to contribute to breast cancer progression and metastasis in various models, but the cellular and molecular mechanisms involved are still undisclosed. Here we show that a high- cholesterol diet promotes intravasation in two mouse models of breast cancer and that this could be reverted by blocking LDL binding to LDLR in tumor cells. Moreover, we show that LDL promotes vascular invasion in vitro and the intercalation of tumor cells with endothelial cells, a phenotypic change resembling vascular mimicry (VM). At the molecular level, LDL increases the expression of SERPINE2, previously shown to be required for both VM and intravasation. Overall, our manuscript unravels novel mechanisms by which systemic hypercholesterolemia may affect the onset of metastatic breast cancer by favouring phenotypic changes in breast cancer cells and increasing intravasation.


Subject(s)
Breast Neoplasms , Receptors, LDL , Animals , Receptors, LDL/metabolism , Receptors, LDL/genetics , Female , Mice , Humans , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Cell Line, Tumor , Neoplasm Invasiveness , Cholesterol, Dietary/adverse effects , Cholesterol, LDL/metabolism , Cholesterol, LDL/blood , Lipoproteins, LDL/metabolism , Cholesterol/metabolism , Cholesterol/blood
8.
J Nutr ; 154(6): 1880-1889, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38599384

ABSTRACT

BACKGROUND: Cholesterol plays a vital role in fetal growth and development during pregnancy. There remains controversy over whether pregnant females should limit their cholesterol intake. OBJECTIVES: The objective of this study was to investigate the association between maternal dietary cholesterol intake during pregnancy and infant birth weight in a Chinese prospective cohort study. METHODS: A total of 4146 mother-child pairs were included based on the Jiangsu Birth Cohort study. Maternal dietary information was assessed with a semiquantitative food-frequency questionnaire. Birth weight z-scores and large-for-gestational-age (LGA) infants were converted by the INTERGROWTH-21st neonatal weight-for-gestational-age standard. Poisson regression and generalized estimating equations were employed to examine the relationships between LGA and maternal dietary cholesterol across the entire pregnancy and trimester-specific cholesterol intake, respectively. RESULTS: The median intake of maternal total dietary cholesterol during the entire pregnancy was 671.06 mg/d, with eggs being the main source. Maternal total dietary cholesterol and egg-sourced cholesterol were associated with an increase in birth weight z-score, with per standard deviation increase in maternal total and egg-sourced dietary cholesterol being associated with an increase of 0.16 [95% confidence interval (CI): 0.07, 0.25] and 0.06 (95% CI: 0.03, 0.09) in birth weight z-score, respectively. Egg-derived cholesterol intake in the first and third trimesters was positively linked to LGA, with an adjusted relative risk of 1.11 (95% CI: 1.04, 1.18) and 1.09 (95% CI: 1.00, 1.18). Compared with mothers consuming ≤7 eggs/wk in the third trimester, the adjusted relative risk for having an LGA newborn was 1.37 (95% CI: 1.09, 1.72) for consuming 8-10 eggs/wk and 1.45 (95% CI: 1.12, 1.86) for consuming >10 eggs/wk (P-trend = 0.015). CONCLUSIONS: Maternal total dietary cholesterol intake, as well as consuming over 7 eggs/wk during pregnancy, displayed significant positive relationships with the incidence of LGA, suggesting that mothers should avoid excessive cholesterol intake during pregnancy to prevent adverse birth outcomes.


Subject(s)
Birth Weight , Cholesterol, Dietary , Eggs , Humans , Female , Pregnancy , Prospective Studies , Cholesterol, Dietary/administration & dosage , Adult , Infant, Newborn , Maternal Nutritional Physiological Phenomena , Diet , Cohort Studies , China , Male , Gestational Age , Fetal Macrosomia/epidemiology , Infant, Large for Gestational Age
9.
Nutrients ; 16(5)2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38474843

ABSTRACT

Cholesterol is a nutrient commonly found in the human diet. The relationship between dietary cholesterol, its sources, and cardiovascular disease (CVD) is still a topic of debate. This study aimed to investigate the association between dietary cholesterol, its sources, and cardiovascular events in a Chinese population. The present study analyzed data from the China Health and Nutrition Survey (CHNS) cohort between 1991 and 2015. This study analyzed data from 3903 participants who were 40 years of age or older at baseline and had no history of cardiovascular disease, diabetes, or hypertension. During a median follow-up of 14 years, 503 cardiovascular disease events were identified through follow-up questionnaires administered every 2-3 years. The events included fatal and nonfatal coronary heart disease, stroke, heart failure, and other cardiovascular disease deaths. Cox regression was used to estimate risk ratios (HR) for CVD events after adjusting for demographic, socioeconomic, and behavioral factors. It was discovered that sources of dietary cholesterol varied among different subgroups of the population. The top three sources of cholesterol among all participants were eggs, red meat, and seafood, accounting for 57.4%, 28.2%, and 9.0% of total daily cholesterol intake, respectively. The present study found that there was a significant association between total dietary cholesterol intake, and the risk of developing cardiovascular disease (adjusted HR [95% CI]: total cholesterol (highest and lowest quartiles compared) 1.57 [1.17-2.11]). Cholesterol from poultry, seafood, and eggs was also significantly associated with a reduced risk of CVD (adjusted HR [95% CI]: poultry 0.18 [0.04-0.82], seafood 0.11 [0.02-0.54], and eggs 0.16 [0.03-0.73]). After adjusting for daily caloric intake, daily fat intake, and daily saturated fat intake, the previously observed association between red meat cholesterol and cardiovascular events (unadjusted HR [95% CI]: 0.44 [0.35-0.55]) was no longer statistically significant (adjusted HR [95% CI]: 0.21 [0.04-1.01]).


Subject(s)
Cardiovascular Diseases , Humans , Cardiovascular Diseases/epidemiology , Cholesterol, Dietary , Diet , Cholesterol , Eating , Risk Factors
11.
Nutr Metab Cardiovasc Dis ; 34(5): 1198-1206, 2024 May.
Article in English | MEDLINE | ID: mdl-38218709

ABSTRACT

BACKGROUND AND AIMS: Although dyslipidemia is a major risk factor for chronic kidney disease (CKD), the relationship between dietary cholesterol and CKD remains unknown. We investigated the association between cholesterol intake and CKD risk. METHODS AND RESULTS: The Korea National Health and Nutrition Examination Survey (KNHANES) 2019-2021 (n = 13,769) and the Korean Genome and Epidemiology Study (KoGES) (n = 9225) data were used for this study. Cholesterol intake was assessed using a 24-h recall food frequency questionnaire, and participants were categorized into three groups (T1, T2, and T3) based on cholesterol intake. Primary outcomes were prevalence and incidence of CKD. Higher cholesterol intake was modestly associated with increased serum levels of total, low-density lipoprotein, and high-density lipoprotein cholesterol in the KNHANES. However, we found no significant association between cholesterol intake and CKD prevalence in the KNHANES, regardless of a history of hypercholesterolemia. In the KoGES, during a median follow-up of 11.4 years, cholesterol intake was not associated with incident CKD in participants without hypercholesterolemia (hazard ratio [HR] per 10 mg increase, 1.00; 95 % confidence interval [CI], 0.99-1.01) and in those with hypercholesterolemia (HR, 1.01; 95 % CI, 0.98-1.04). Egg consumption also showed no significant association with the risk of incident CKD. Additionally, cholesterol intake had no significant interaction on the relationships between serum cholesterol levels and incident CKD. CONCLUSION: Although cholesterol intake was associated with increased serum cholesterol levels, it was not associated with CKD prevalence and incidence. Our findings suggest that reducing cholesterol intake alone may not be sufficient to prevent CKD.


Subject(s)
Hypercholesterolemia , Renal Insufficiency, Chronic , Humans , Cholesterol, Dietary/adverse effects , Hypercholesterolemia/diagnosis , Hypercholesterolemia/epidemiology , Nutrition Surveys , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Risk Factors , Cohort Studies , Republic of Korea/epidemiology , Glomerular Filtration Rate
12.
PLoS One ; 19(1): e0295212, 2024.
Article in English | MEDLINE | ID: mdl-38207245

ABSTRACT

Previous research has shown that natural medications pose health risks, especially in subjects with comorbidities. This study aimed to evaluate the safety of saffron ethanolic extract (SEE) administration in early and established atherosclerotic rabbits. Rabbits were given a high-cholesterol diet (HCD) for 4 and 8 weeks to induce early and established atherosclerosis respectively, and then they were treated with 50 and 100 mg/kg/day SEE. The body weight of the animals was recorded. Blood samples were collected at baseline, pre-treatment, and post-treatment for hematological studies, lipid profiles, and biochemical profiles. Tissue specimens of the vital organs were subjected to histological examination. The above parameters were significantly altered post-intervention with 4 and 8 weeks of HCD. No significant differences in body weight were observed in all the groups post-treatment with 50 and 100mg/kg of SEE compared to pre-treatment. However, low-density lipoprotein cholesterol, total cholesterol, serum urea, and glucose significantly decreased post-treatment with 50 and 100mg/kg/day SEE compared to pre-treatment in early and established atherosclerosis groups. Hematological parameters that were affected post-intervention with HCD returned to their baseline values post-treatment with 50 and 100mg/kg/day SEE. There was a significant improvement in the vital organs post-treatment with 50 and 100mg/kg SEE. SEE can safely be administered without causing harmful effects on the hematological, biochemical profiles, and vital organs. Notably, SEE exerts hypolipidemic and hypoglycemic effects on atherosclerotic conditions. Further clinical trials are warranted to ensure the safety of saffron administration in patients with atherosclerosis-related diseases.


Subject(s)
Atherosclerosis , Crocus , Hypercholesterolemia , Hyperlipidemias , Humans , Rabbits , Animals , Cholesterol , Atherosclerosis/pathology , Body Weight , Cholesterol, Dietary
14.
Mar Drugs ; 21(12)2023 Nov 29.
Article in English | MEDLINE | ID: mdl-38132943

ABSTRACT

Aberrantly high dietary cholesterol intake and intestinal cholesterol uptake lead to dyslipidemia, one of the risk factors for cardiovascular diseases (CVDs). Based on previous studies, laminarin, a polysaccharide found in brown algae, has hypolipidemic activity, but its underlying mechanism has not been elucidated. In this study, we investigated the effect of laminarin on intestinal cholesterol uptake in vitro, as well as the lipid and morphological parameters in an in vivo model of high-fat diet (HFD)-fed mice, and addressed the question of whether Niemann-Pick C1-like 1 protein (NPC1L1), a key transporter mediating dietary cholesterol uptake, is involved in the mechanistic action of laminarin. In in vitro studies, BODIPY-cholesterol-labeled Caco-2 cells were examined using confocal microscopy and a fluorescence reader. The results demonstrated that laminarin inhibited cholesterol uptake into Caco-2 cells in a concentration-dependent manner (EC50 = 20.69 µM). In HFD-fed C57BL/6J mice, laminarin significantly reduced the serum levels of total cholesterol (TC), total triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C). It also decreased hepatic levels of TC, TG, and total bile acids (TBA) while promoting the excretion of fecal cholesterol. Furthermore, laminarin significantly reduced local villous damage in the jejunum of HFD mice. Mechanistic studies revealed that laminarin significantly downregulated NPC1L1 protein expression in the jejunum of HFD-fed mice. The siRNA-mediated knockdown of NPC1L1 attenuated the laminarin-mediated inhibition of cholesterol uptake in Caco-2 cells. This study suggests that laminarin significantly improves dyslipidemia in HFD-fed mice, likely by reducing cholesterol uptake through a mechanism that involves the downregulation of NPC1L1 expression.


Subject(s)
Diet, High-Fat , Dyslipidemias , Humans , Mice , Animals , Diet, High-Fat/adverse effects , Cholesterol, Dietary/metabolism , Niemann-Pick C1 Protein/metabolism , Caco-2 Cells , Mice, Inbred C57BL , Cholesterol/metabolism , Triglycerides/metabolism , Liver/metabolism , Membrane Transport Proteins/metabolism
15.
Am J Clin Nutr ; 118(5): 966-976, 2023 11.
Article in English | MEDLINE | ID: mdl-37923501

ABSTRACT

BACKGROUND: Higher dietary cholesterol intake during pregnancy increases risk of gestational diabetes mellitus (GDM). However, no studies have investigated interindividual variability in cholesterol metabolism and the association of genetics and diet on GDM. OBJECTIVE: ; To prospectively evaluate the joint association of cholesterol-rich dietary patterns and polymorphisms of genes coding for cholesterol metabolism pathway proteins with GDM. METHODS: A total of 1116 pregnant females from the Tongji Birth Cohort were enrolled. GDM was diagnosed according to a 75-g 2-h oral glucose tolerance test at 24-28 wk of gestation. Dietary data were collected by a validated food frequency questionnaire. The reduced-rank regression method was used to identify dietary patterns using dietary cholesterol as the response variable. Time-of-flight mass spectrometry was used for genotyping. The genetic risk score (GRS) for GDM was constructed with genetic variants in 28 cholesterol metabolism-related single-nucleotide polymorphisms (SNPs). Conditional logistic regression models were used to assess the odds ratio (OR) for GDM. RESULTS: The cholesterol-rich dietary pattern was rich in livestock and poultry meat and eggs but lower in cereals. The multivariable-adjusted ORs for GDM were 1.24 (95% confidence interval: 1.06-1.44) per SD increment of cholesterol-rich pattern scores and 1.28 (1.09-1.49) per tertile GRS. The variants of the CYP7A1 rs3808607 G→T/rs8192871 G→A/rs7833904 A→T, as well as AGGG and TTGA haplotypes of 4 CYP7A1-spanning SNPs, were significantly associated with GDM. For the joint effect, the OR was 3.53 (1.71-7.31) in the highest categories of both dietary pattern scores and GRS compared with individuals with the lowest strata without significant interaction (P for interaction = 0.101). CONCLUSIONS: Both a cholesterol-rich dietary pattern and genetic variants of cholesterol metabolism genes are associated with risk of GDM. Adherence to a cholesterol-rich dietary pattern during early pregnancy promotes the chance of GDM, especially in women with higher GRS. CLINICAL TRIAL REGISTRY: This trial was registered at http://www.chictr.org.cn (Registration number: ChiCTR1800016908). URL: =https://www.chictr.org.cn/showprojEN.html?proj=28081.


Subject(s)
Diabetes, Gestational , Pregnancy , Female , Humans , Diabetes, Gestational/genetics , Case-Control Studies , Cholesterol, Dietary , Maternal Nutritional Physiological Phenomena , Diet , Risk Factors , Genetic Variation
16.
Science ; 382(6671): eadf0966, 2023 11 10.
Article in English | MEDLINE | ID: mdl-37943936

ABSTRACT

Intestinal absorption is an important contributor to systemic cholesterol homeostasis. Niemann-Pick C1 Like 1 (NPC1L1) assists in the initial step of dietary cholesterol uptake, but how cholesterol moves downstream of NPC1L1 is unknown. We show that Aster-B and Aster-C are critical for nonvesicular cholesterol movement in enterocytes. Loss of NPC1L1 diminishes accessible plasma membrane (PM) cholesterol and abolishes Aster recruitment to the intestinal brush border. Enterocytes lacking Asters accumulate PM cholesterol and show endoplasmic reticulum cholesterol depletion. Aster-deficient mice have impaired cholesterol absorption and are protected against diet-induced hypercholesterolemia. Finally, the Aster pathway can be targeted with a small-molecule inhibitor to manipulate cholesterol uptake. These findings identify the Aster pathway as a physiologically important and pharmacologically tractable node in dietary lipid absorption.


Subject(s)
Cholesterol, Dietary , Enterocytes , Intestinal Absorption , Membrane Transport Proteins , Animals , Mice , Biological Transport , Cholesterol, Dietary/metabolism , Intestinal Absorption/drug effects , Intestinal Absorption/physiology , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Mice, Inbred C57BL , Enterocytes/metabolism , Liver X Receptors/metabolism , Humans , Jejunum/metabolism , Mice, Knockout
18.
J Prev Alzheimers Dis ; 10(4): 748-755, 2023.
Article in English | MEDLINE | ID: mdl-37874096

ABSTRACT

BACKGROUND: Dietary cholesterol has been confirmed to be associated with high risks of diabetes, hypertension, and stroke, but whether it is detrimental to cognitive health is highly debated. This study aimed to investigate the associations between dietary cholesterol and all-cause dementia and AD dementia. METHODS: This prospective study analyzed Framingham Offspring Study cohort (FOS) participants who were dementia-free at baseline and had detailed information on daily diet (measured by food frequency questionnaires) and demographic characteristics. Surveillance for incident dementia commenced at examination 5 (1991-1995) through 2018 and continued for approximately 30 years. RESULTS: A total of 3249 subjects were included with a mean age of 54.7 years (SD: 9.8). During a median follow-up of 20.2 years (interquartile range: 14.2-24.8), a total of 312 incident dementia events occurred, including 211 (67.7%) cases of AD dementia. After multivariate adjustments for established dementia risk factors, participants with the highest intake of dietary cholesterol had a lower risk of all-cause dementia (HR: 0.70; 95% CI: 0.57-0.93) and AD dementia (HR: 0.68; 95% CI: 0.60-0.88) relative to individuals with the lowest intake. However, the associations were not significant for the group with a medium intake of dietary cholesterol. CONCLUSION: High intake of dietary cholesterol was associated with a decreased risk of all-cause dementia and AD dementia. The findings of this observational study need to be confirmed by other studies to highlight the role of dietary cholesterol in the development of neurodegenerative diseases.


Subject(s)
Alzheimer Disease , Dementia , Humans , Middle Aged , Dementia/epidemiology , Dementia/etiology , Dementia/prevention & control , Alzheimer Disease/epidemiology , Alzheimer Disease/etiology , Alzheimer Disease/prevention & control , Cholesterol, Dietary/adverse effects , Prospective Studies , Risk Factors
19.
J Nutr Sci ; 12: e97, 2023.
Article in English | MEDLINE | ID: mdl-37706071

ABSTRACT

Whilst dietary cholesterol guidelines have waivered through the years with historic restrictions lifted for the majority of the general population, recommendations to reduce saturated fat intake have been the mainstay of dietary guidelines since the 1980s and were recently reinforced by the Scientific Advisory Committee on Nutrition (SACN). Cholesterol metabolism is complex, with saturated fat known to have a more significant contribution at raising levels of low-density lipoprotein (LDL) cholesterol, a well-established risk factor for cardiovascular disease (CVD). However, it is clear from metabolic research that hyper-responsiveness to both dietary cholesterol and saturated fat exists; hence, for specific subsets of the population, reductions in both nutrients may be indicated. With this in mind, the current article aims to provide an overview of the mechanisms underlying biological variation in responsiveness and introduces research currently underway which will hopefully identify simple biomarkers that can be used to predict responsiveness and permit tailored, personalised, dietary advice. Eggs are a well-known source of dietary cholesterol whilst being low in saturated fat. A common question encountered in clinical practice is must individuals limit intake to manage blood cholesterol levels. This article summarises key recent papers which confirm that eggs can be enjoyed as part of a healthy balanced diet, whilst highlighting the need for further research in certain population groups, e.g. in individuals with diabetes.


Subject(s)
Cardiovascular Diseases , Dietary Fats , Humans , Cholesterol, Dietary , Cholesterol , Diet
20.
J Alzheimers Dis ; 95(2): 625-640, 2023.
Article in English | MEDLINE | ID: mdl-37574736

ABSTRACT

BACKGROUND: The association between dietary or serum cholesterol and cognitive performance in older adults has not been well-established. OBJECTIVE: This study aimed to investigate the potential association between dietary or serum cholesterol and cognitive performance in the elderly population. METHODS: A cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2012 and 2013-2014. Diet and supplement cholesterol was estimated based on two non-consecutive 24-hour dietary recalls. Cognitive function was assessed using various statistical tests. Poor cognitive performance was defined as scores below the lowest quartile within age groups. Regression models were adjusted for demographic factors, and subgroup analyses were performed for non-Hispanic White (NHW) and non-Hispanic Black (NHB) individuals. RESULTS: Among 759 participants aged 60 years and above, dietary cholesterol was only associated with dietary saturated fatty acids and serum high-density lipoprotein cholesterol. There was no evidence of an association between dietary cholesterol and cognitive function, except for NHB individuals, where dietary cholesterol showed a positive correlation with cognitive function. In the overall sample and NHW participants, there were consistent positive associations between serum total cholesterol and cognitive performance across statistical tests, while such associations were rare among NHB individuals. Although not statistically significant, NHB individuals had higher dietary/supplementary/total cholesterol intake compared with NHW individuals. CONCLUSION: Within the normal range, increasing serum cholesterol may be a potential factor to prevent or relieve cognitive dysfunction. However, ethnic differences should be taken into account when considering the association between cholesterol and cognitive performance.


Subject(s)
Cholesterol, Dietary , Diet , Humans , Aged , Nutrition Surveys , Cross-Sectional Studies , Cholesterol , Cognition , White
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