cytellin and Obesity

Non-cholesterol sterols are validated biomarkers for intestinal cholesterol absorption and endogenous cholesterol synthesis. However, their use in metabolic disturbances has not been systematically explored. Therefore, we conducted a systematic review to provide an overview of non-cholesterol sterols as markers for cholesterol metabolism in different metabolic disorders. Potentially relevant studies were retrieved by a systematic search of three databases in July 2018 and ninety-four human studies were included. Cholesterol-standardized levels of campesterol, sitosterol and cholestanol were collected to reflect cholesterol absorption and those of lathosterol and desmosterol to reflect cholesterol synthesis. Their use as biomarkers was examined in the following metabolic disorders: overweight/obesity (

Topics: Biomarkers; Cardiovascular Diseases; Cholesterol; Desmosterol; Diabetes Mellitus; Humans; Intestinal Absorption; Intestinal Diseases; Kidney Diseases; Liver Diseases; Metabolic Diseases; Obesity; Overweight; Phytosterols; Sitosterols; Sterols

The physiological roles of phytosterols in chronic inflammation, which are believed to be involved in the underlying mechanisms for metabolic diseases, have yet to be elucidated. Therefore, in the present study, we aimed to elucidate the physiological roles of phytosterols in both clinical studies and animal experiments. We observed the existence of rather specific negative correlations between the serum sitosterol level and the serum IL-6 and the TNF-α levels in both diabetic subjects (n=46) and non-diabetic subjects (n=178). Multiple regression analyses also revealed that the serum IL-6 and TNF-α levels exhibited strong negative correlations with the serum sitosterol levels. When ABCG5/8 KO mice with markedly elevated plasma sitosterol levels and ABCG5/8 hetero mice were fed a high-fat diet, we observed that the increase in body weight, the fatty liver changes, and the expansion of perigonadal adipose tissues were suppressed in ABCG5/8 KO mice without any modulation of food intake. We also observed that the plasma IL-6 and TNF-α levels, the expressions of TNF-α and PAI-1 in the liver and the expressions of the IL-6, TNF-α, and MCP-1 levels in the adipose tissue were lower in ABCG5/8 KO mice. These results suggest that sitosterol might suppress obesity-related chronic inflammation and might be applicable to the treatment of metabolic diseases.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily G, Member 5; Chronic Disease; Female; Humans; Inflammation; Interleukin-6; Lipoproteins; Male; Mice; Mice, Knockout; Middle Aged; Obesity; Sitosterols; Tumor Necrosis Factor-alpha

The aim of this study was to assess the influence of increased plant stanol ester intake on lipid profile and serum ratio of non-cholesterol sterols to cholesterol in obese women (50 years of age) with dyslipidemia.. 90 females were assigned into 2 treatment groups: For a period of 4 weeks, group 1 was receiving a yoghurt, enriched with 2 g of plant stanol ester (PS group), and group 2 was receiving a yoghurt drink without extra stanols. Anthropometric measurements included body height and weight. Lipid profile was determined by commercially available enzymatic methods. Serum non-cholesterol sterols and stanols concentrations were quantitated by gas chromatography. The study was single-blind and placebo-controlled.. The yoghurt drink enriched with plant stanol ester significantly reduced serum total cholesterol, LDL cholesterol, and non-HDL cholesterol levels (p < 0.05). No changes were observed in HDL cholesterol and triacylglycerol levels. The highest drop of LDL cholesterol was noted in the upper quartile of total cholesterol concentrations. In the PS group the statistically significant (p < 0.0001) changes were also observed in serum ratios of non-cholesterol sterols to cholesterol: campesterol, sitosterol, sitostanol, and avenasterol.. Plant stanol esters influence the concentration of total cholesterol, particularly LDL cholesterol. This effect seems to be related to the reduced dietary cholesterol absorption.

Topics: Administration, Oral; Anticholesteremic Agents; Dyslipidemias; Female; Humans; Lipids; Middle Aged; Obesity; Sitosterols; Sterols; Treatment Outcome

We examined serum cholesterol synthesis and absorption markers and their association with neonatal birth weight in obese pregnancies affected by gestational diabetes mellitus (GDM). Pregnant women at risk for GDM (BMI >30 kg/m²) were enrolled from maternity clinics in Finland. GDM was determined from the results of an oral glucose tolerance test. Serum samples were collected at six time-points, one in each trimester of pregnancy, and at 6 weeks, 6 months, and 12 months postpartum. Analysis of serum squalene and noncholesterol sterols by gas-liquid chromatography revealed that in subjects with GDM (n = 22), the serum Δ8-cholestenol concentration and lathosterol/sitosterol ratio were higher (P < 0.05) than in the controls (n = 30) in the first trimester, reflecting increased cholesterol synthesis. Also, subjects with GDM had an increased ratio of squalene to cholesterol (100 × μmol/mmol of cholesterol) in the second (11.5 ± 0.5 vs. 9.1 ± 0.5, P < 0.01) and third (12.1 ± 0.8 vs. 10.0 ± 0.7, P < 0.05) trimester. In GDM, the second trimester maternal serum squalene concentration correlated with neonatal birth weight (r = 0.70, P < 0.001). In conclusion, in obesity, GDM associated with elevated serum markers of cholesterol synthesis. Correlation of maternal serum squalene with neonatal birth weight suggests a potential contribution of maternal cholesterol synthesis to newborn weight in GDM.

Topics: Adult; Biomarkers; Birth Weight; Body Mass Index; Cholesterol; Diabetes, Gestational; Female; Fetal Macrosomia; Finland; Follow-Up Studies; Humans; Infant, Newborn; Male; Maternal Nutritional Physiological Phenomena; Obesity; Phytosterols; Postpartum Period; Pregnancy; Risk; Sitosterols; Squalene

Plant sterols (PSs) cannot be synthesized in mammals and are exclusively diet-derived. PSs cross the blood-brain barrier and may have anti-neuroinflammatory effects. Obesity is linked to lower intestinal uptake and blood levels of PSs, but its effects in terms of neuroinflammation-if any-remain unknown. We investigated the effect of high-fat diet-induced obesity on PSs in the brain and the effects of the PSs campesterol and β-sitosterol on in vitro microglia activation. Sterols (cholesterol, precursors, PSs) and polyunsaturated fatty acid-derived lipid mediators were measured in the food, blood, liver and brain of C57BL/6J mice. Under a PSs-poor high-fat diet, PSs levels decreased in the blood, liver and brain (>50%). This effect was reversible after 2 weeks upon changing back to a chow diet. Inflammatory thromboxane B2 and prostaglandin D2 were inversely correlated to campesterol and β-sitosterol levels in all brain regions. PSs content was determined post mortem in human cortex samples as well. In vitro, PSs accumulate in lipid rafts isolated from SIM-A9 microglia cell membranes. In summary, PSs levels in the blood, liver and brain were associated directly with PSs food content and inversely with BMI. PSs dampen pro-inflammatory lipid mediators in the brain. The identification of PSs in the human cortex in comparable concentration ranges implies the relevance of our findings for humans.

Topics: Animal Feed; Animals; Cells, Cultured; Cholesterol; Chromatography, Liquid; Diet, High-Fat; Disease Models, Animal; Fatty Acids, Unsaturated; Humans; Lipidomics; Liver; Male; Mice; Mice, Inbred C57BL; Microglia; Neuroinflammatory Diseases; Obesity; Phytosterols; Sitosterols; Tandem Mass Spectrometry

β-sitosterol (SIT), the most abundant bioactive component of vegetable oil and other plants, is a highly potent antidiabetic drug. Our previous studies show that SIT controls hyperglycemia and insulin resistance by activating insulin receptor and glucose transporter 4 (GLUT-4) in the adipocytes of obesity induced type 2 diabetic rats. The current research was undertaken to investigate if SIT could also exert its antidiabetic effects by circumventing adipocyte induced inflammation, a key driving factor for insulin resistance in obese individuals. Effective dose of SIT (20 mg/kg b.wt) was administered orally for 30 days to high fat diet and sucrose induced type-2 diabetic rats. Metformin, the conventionally used antidiabetic drug was used as a positive control. Interestingly, SIT treatment restores the elevated serum levels of proinflammatory cytokines including leptin, resistin, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to normalcy and increases anti-inflammatory adipocytokines including adiponectin in type 2 diabetic rats. Furthermore, SIT decreases sterol regulatory element binding protein-1c (SREBP-1c) and enhances Peroxisome Proliferator-activated receptor-γ (PPAR-γ) gene expression in adipocytes of diabetic rats. The gene and protein expression of c-Jun-N-terminal kinase-1 (JNK1), inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) and nuclear factor kappa B (NF-κB) were also significantly attenuated in SIT treated groups. More importantly, SIT acts very effectively as metformin to circumvent inflammation and insulin resistance in diabetic rats. Our results clearly show that SIT inhibits obesity induced insulin resistance by ameliorating the inflammatory events in the adipose tissue through the downregulation of IKKβ/NF-κB and c-Jun-N-terminal kinase (JNK) signaling pathway.

Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Body Weight; Cytokines; Diabetes Mellitus, Type 2; Diet, High-Fat; Down-Regulation; Feeding Behavior; I-kappa B Kinase; Inflammation; Inflammation Mediators; Insulin Resistance; Male; MAP Kinase Signaling System; Molecular Docking Simulation; NF-kappa B; Obesity; PPAR gamma; Rats; RNA, Messenger; Sitosterols; Sterol Regulatory Element Binding Protein 1; Sucrose; Up-Regulation

Changes in cholesterol absorption and cholesterol synthesis may promote dyslipidemia and cardiovascular disease in individuals with type 2 diabetes mellitus (T2DM).. To assess cholesterol synthesis and absorption in lean individuals, obese individuals, and individuals with T2DM.. We measured lathosterol and lanosterol (markers of cholesterol synthesis) as well as campesterol and β-sitosterol (markers of cholesterol absorption) in the serum of 15 to 26 years old individuals with T2DM (n = 95), as well as their lean (n = 98) and obese (n = 92) controls.. Individuals with T2DM showed a 51% increase in lathosterol and a 65% increase in lanosterol compared to lean controls. Similarly, obese individuals showed a 31% increase in lathosterol compared to lean controls. Lathosterol and lanosterol were positively correlated with body mass index, fasting insulin and glucose, serum triglycerides, and C-reactive protein, and negatively correlated with HDL-cholesterol. In contrast, campesterol and β-sitosterol were not altered in individuals with T2DM. Moreover, campesterol and β-sitosterol were negatively correlated with body mass index, fasting insulin, and C-reactive protein and were positively correlated with HDL-cholesterol.. Adolescents and young adults with T2DM show evidence of increased cholesterol synthesis compared to non-diabetic lean controls. These findings suggest that T2DM may promote cardiovascular disease by increasing cholesterol synthesis, and provide additional rationale for the use of cholesterol synthesis inhibitors in this group.

Topics: Adolescent; Adult; Biomarkers; Body Mass Index; Case-Control Studies; Cholesterol; Diabetes Mellitus, Type 2; Humans; Obesity; Phytosterols; Sitosterols; Young Adult

Impaired glucose metabolism during pregnancy may associate with changes in fetal cholesterol metabolism. We investigated if gestational diabetes mellitus (GDM) affects newborn cholesterol metabolism as determined by cord blood squalene and non-cholesterol sterols. Furthermore, we examined potential correlations between cord blood and maternal serum non-cholesterol sterols.. Pregnant women at risk for GDM (BMI>30 kg/m. The ratios of squalene and non-cholesterol sterols to cholesterol (100 × μmol/mmol of cholesterol) in cord blood did not differ between the infants born to mothers with GDM (n = 15) or mothers with normal glucose tolerance (n = 13). The ratios of sitosterol and campesterol to cholesterol in the cord blood correlated with the corresponding maternal serum ratios (r = 0.70, p < 0.0001) in both groups.. In obese women under good glycaemic control, GDM did not affect newborn cholesterol metabolism. Cord blood sitosterol and campesterol ratios to cholesterol correlated with the corresponding maternal serum ratios thus potentially reflecting maternal-fetal cholesterol transport.

Topics: Adult; Biomarkers; Blood Glucose; Case-Control Studies; Cholestanol; Cholesterol; Diabetes, Gestational; Female; Fetal Blood; Finland; Humans; Infant, Newborn; Maternal-Fetal Exchange; Obesity; Phytosterols; Pregnancy; Sitosterols; Squalene

Topics: Bile; Humans; Liver; Non-alcoholic Fatty Liver Disease; Obesity; Sitosterols

Obesity is associated with increased systemic and airway oxidative stress, which may result from a combination of adipokine imbalance and antioxidant defenses reduction. Obesity-mediated oxidative stress plays an important role in the pathogenesis of dyslipidemia, vascular disease, and nonalcoholic hepatic steatosis. The antidyslipidemic activity of pigeon pea were evaluated by high-fat diet (HFD) hamsters model, in which the level of high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and total triglyceride (TG) were examined. We found that pigeon pea administration promoted cholesterol converting to bile acid in HFD-induced hamsters, thereby exerting hypolipidemic activity. In the statistical results, pigeon pea significantly increased hepatic carnitine palmitoyltransferase-1 (CPT-1), LDL receptor, and cholesterol 7α-hydroxylase (also known as cytochrome P450 7A1, CYP7A1) expression to attenuate dyslipidemia in HFD-fed hamsters; and markedly elevated antioxidant enzymes in the liver of HFD-induced hamsters, further alleviating lipid peroxidation. These effects may attribute to pigeon pea contained large of unsaturated fatty acids (UFA; C18:2) and phytosterol (β-sitosterol, campesterol, and stigmasterol). Moreover, the effects of pigeon pea on dyslipidemia were greater than β-sitosterol administration (4%), suggesting that phytosterone in pigeon pea could prevent metabolic syndrome.

Topics: Animals; Antioxidants; Cajanus; Carnitine O-Palmitoyltransferase; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cholesterol, HDL; Cholesterol, LDL; Chromatography, High Pressure Liquid; Cricetinae; Diet, High-Fat; Disease Models, Animal; Hypercholesterolemia; Lipid Peroxidation; Liver; Male; Obesity; Oxidative Stress; Phytosterols; Receptors, LDL; Sitosterols; Stigmasterol; Triglycerides

Non-alcoholic fatty liver disease (NAFLD) is associated with impaired glucose and lipoprotein metabolism. However, the metabolism of cholesterol in NAFLD remains unexplored. We investigated how fatty liver influences cholesterol metabolism in 242 non-diabetic subjects.. Liver fat content was measured with proton magnetic resonance spectroscopy. Cholesterol metabolism was assayed with serum non-cholesterol sterols, surrogate markers of cholesterol synthesis and absorption. The analyses were performed with gas-liquid chromatography.. A total of 114 subjects had NAFLD and 128 subjects had normal liver fat content. Non-cholesterol sterols reflecting cholesterol synthesis (cholestenol, desmosterol, and lathosterol) were higher, and those reflecting cholesterol absorption (cholestanol and plant sterols) were lower in subjects with NAFLD than in controls, independent of body mass index. Liver fat content was positively associated with markers of cholesterol synthesis (r = from 0.262 to 0.344, p < 0.001 for all) and inversely associated with markers of cholesterol absorption (r = from -0.299 to -0.336, p < 0.001 for all). In the entire study group, synthesis and absorption markers were interrelated, indicating that the homeostasis of cholesterol metabolism was maintained. LDL cholesterol was similar in the two groups.. We demonstrated that although LDL cholesterol concentrations are unchanged, cholesterol metabolism in NAFLD is characterized by increased synthesis and diminished absorption of cholesterol. These changes are associated with liver fat content independent of body weight.

Topics: Adult; Aged; Body Mass Index; Case-Control Studies; Cholesterol; Cholesterol, Dietary; Cholesterol, LDL; Fatty Liver; Female; Humans; Insulin; Intestinal Absorption; Liver; Magnetic Resonance Spectroscopy; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Sitosterols; Young Adult

The objective of this study was to determine the effects of disodium ascorbyl phytostanyl phosphate (DAPP), a novel hydrophilic phytostanol analogue, on energy homeostasis, including body weight and intestinal energy absorption, and plasma triglyceride concentrations, in hamsters.. Male Golden Syrian hamsters (n = 50) were fed for 5 weeks with experimental diets varying in cholesterol and phytostanol content. Diets included (i) non-cholesterol (semipurified diet without added cholesterol), (ii) cholesterol-control (semipurified diet with 0.25% cholesterol), (iii) stanol (cholesterol-control with 1% free phytostanols), (iv) DAPP 0.7% (cholesterol-control with 0.71% DAPP) or (v) DAPP 1.4% (cholesterol-control with 1.43% DAPP). Fecal samples were collected continuously for 3 days on week 3, and fecal energy output was measured by bomb calorimetry.. Hamsters fed 1.4% DAPP gained less (P<0.05) weight than hamsters fed non-cholesterol and stanol diets. Diets had no effect on total food consumption or gross energy intake after 5 weeks, but lower (P<0.05) weekly food consumptions in hamsters fed 1.4% DAPP were observed at weeks 1 and 2 of the experiment in comparison to animals fed the non-cholesterol diet. In comparison to non-cholesterol and cholesterol-control diets, DAPP 1.4% increased (P<0.01) fecal energy output by 47 and 46%, respectively. In hamsters supplemented with 1.4% DAPP, plasma triglyceride concentrations were 45% lower (P<0.05) than in cholesterol-control fed hamsters. Furthermore, plasma triglyceride levels in the DAPP 1.4% group was 49% lower (P<0.01) than in the stanol group, despite the fact that both diets contained equivalent amounts of phytostanols. The lower concentration of DAPP (0.7%) also reduced plasma triglycerides (P<0.05) compared with the stanol diet.. Stanol-ascorbate decreases body weight gain in hamsters, likely due to lower energy absorption at the intestinal level. In addition to its previously observed powerful cholesterol-lowering effect, DAPP has a hypotriglyceridemic function in hamsters.

Topics: Animals; Calorimetry; Cholesterol, Dietary; Cricetinae; Diet, Reducing; Eating; Energy Metabolism; Feces; Hypolipidemic Agents; Intestinal Mucosa; Male; Mesocricetus; Obesity; Phytosterols; Random Allocation; Sitosterols; Triglycerides

Because dietary fat appears to be an effective vehicle for dispensing plant sterols into the diet, a special plant-sterol-containing ingredient has recently been developed. This ingredient is a plant sterol suspension in oil in which the sterols are in microcrystalline form. The objective of the present study was to analyse the cholesterol-lowering effects and safety of two different plant sterol preparations, an orally administered microcrystalline plant sterol suspension (MPS) in rapeseed oil and a powdered plant sterol supplement, in obese Zucker rats. Dietary plant sterol supplements (0.5%, w/w) were given concurrently with a high cholesterol diet (HCD, 1% cholesterol and 18% fat, w/w). No significant changes in serum triglyceride, blood glucose, serum glutamate oxaloacetic transaminase and glutamic pyruvic transaminase values or body and liver weights were observed. The powdered plant sterol supplement lowered the serum cholesterol by 25% (P < 0.05) and the MPS diet by 35% (P < 0.001) compared with HCD by the end of the 12-week experiment. Interestingly, the plant sterol supplements also produced a marked reduction in serum ubiquinone levels, suggesting a possible effect on isoprene synthesis. Unlike the powdered plant sterol, both MPS and plain rapeseed oil decreased the serum baseline diene conjugation values, suggesting that they protect against oxidative stress-induced lipid peroxidation in rats. This lipid peroxidation diminishing effect is probably due to some antioxidative components in rapeseed oil. These findings indicate that an unesterified plant sterol, such as the microcrystalline suspension in oil, effectively prevents cholesterol absorption in obese Zucker rats.

Topics: Administration, Oral; Animals; Chemistry, Pharmaceutical; Cholesterol, Dietary; Fatty Acids, Monounsaturated; Female; Hypercholesterolemia; Hypolipidemic Agents; Intestinal Absorption; Lipid Peroxidation; Obesity; Phytosterols; Plant Oils; Powders; Rapeseed Oil; Rats; Rats, Zucker; Sitosterols

The effects of acute caloric restriction on cholesterol balance and kinetics of plasma cholesterol specific activity were investigated in five hyperlipemic subjects with varying degrees of obesity. Caloric restriction decreased plasma triglycerides by 41 +/- 12%, plasma cholesterol by 11 +/- 9%, and the ratio of esterified to free cholesterol by 12 +/- 7+. Immediately on institution of caloric restriction there appeared to be an influx of tissue cholesterol into plasma and a reduction in endogenous synthesis of cholesterol. The cholesterol balance decreased from 1,469 +/- 441 to 1,212 +/- 349 mg/day and the rate of decay of plasma cholesterol specific activity decreased 62 +/- 3%. The effect of caloric restriction on hepatic synthesis of bile acids was also very prompt. The total fecal bile acids were reduced immediately by 36 +/- 7%. Because the effect on fecal excretion of deoxycholic acid was greater than that on fecal lithocholic acid, it was suggested that hepatic synthesis of cholic acid was reduced more than the synthesis of chenodeoxycholic acid. Caloric restriction did not cause any change in the percentage of absorption of dietary cholesterol (40 +/- 2% versus 42 +/- 3%). These observations are in accord with our model relating cholesterol metabolism with the metabolism of plasma lipoproteins in man.

Topics: Adult; Bile Acids and Salts; Cholesterol; Cholesterol Esters; Cholesterol, Dietary; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Energy Intake; Feces; Humans; Hypercholesterolemia; Hyperlipidemias; Kinetics; Male; Middle Aged; Obesity; Sitosterols; Steroids; Triglycerides

An experiment was undertaken to test whether in severe obesity cholesterol production rates obtained by isotope kinetic analysis (two-pool compartmental analysis) are comparable to those measured by chemical sterol balance techniques. Eight severely obese but normocholesterolemic patients were studied by the balance method, and five of these eight were studied by compartmental analysis. Cholesterol turnover was 10% higher by compartmental analysis. In the entire group of eight patients cholesterol turnover was greater than twice that found previously in nonobese patients studied under similar conditions with bile acids and neutral sterols both participating in the increase. This increment was directly related to excess body fat and to adipose cellularity, with correlation co-efficients of 0.66 and 0.72, respectively. The amount of cholesterol in the slowly turning over pool B was related to degree of adiposity, but that in plasma and in pool A did not differ from values in nonobese patients.

Topics: Adipose Tissue; Adult; Body Weight; Carbon Isotopes; Cholesterol; Cholesterol, Dietary; Diet; Feces; Female; Humans; Kinetics; Male; Methods; Middle Aged; Obesity; Sitosterols; Steroids; Time Factors; Tritium