Human adipocyte differentiation and composition of disease-relevant lipids are regulated by miR-221-3p.

MicroRNA-221-3p (miR-221-3p) is associated with both metabolic diseases and cancers. However, its role in terminal adipocyte differentiation and lipid metabolism are uncharacterized. miR-221-3p or its inhibitor was transfected into differentiating or mature human adipocytes. Triglyceride (TG) content and adipogenic gene expression were monitored, global lipidome analysis was carried out, and mechanisms underlying the effects of miR-221-3p were investigated. Finally, cross-talk between miR-221-3p expressing adipocytes and MCF-7 breast carcinoma (BC) cells was studied, and miR-221-3p expression in tumor-proximal adipose biopsies from BC patients analyzed. miR-221-3p overexpression inhibited terminal differentiation of adipocytes, as judged from reduced TG storage and gene expression of the adipogenic markers SCD1, GLUT4, FAS, DGAT1/2, AP2, ATGL and AdipoQ, whereas the miR-221-3p inhibitor increased TG storage. Knockdown of the predicted miR-221-3p target, 14-3-3γ, had similar antiadipogenic effects as miR-221-3p overexpression, indicating it as a potential mediator of mir-221-3p function. Importantly, miR-221-3p overexpression inhibited de novo lipogenesis but increased the concentrations of ceramides and sphingomyelins, while reducing diacylglycerols, concomitant with suppression of sphingomyelin phosphodiesterase, ATP citrate lyase, and acid ceramidase. miR-221-3p expression was elevated in tumor proximal adipose tissue from patients with invasive BC. Conditioned medium of miR-221-3p overexpressing adipocytes stimulated the invasion and proliferation of BC cells, while medium of the BC cells enhanced miR-221-3p expression in adipocytes. Elevated miR-221-3p impairs adipocyte lipid storage and differentiation, and modifies their ceramide, sphingomyelin, and diacylglycerol content. These alterations are relevant for metabolic diseases but may also affect cancer progression.

The association of the lipidomic profile with features of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) affects up to 18% of reproductive-aged women with reproductive and metabolic complications. While lipidomics can identify associations between lipid species and metabolic diseases, no research has examined the association of lipid species with the pathophysiological features of PCOS. The aim of this study was to examine the lipidomic profile in women with and without PCOS. This study was a cross-sectional study in 156 age-matched pre-menopausal women (18-45 years, BMI >20 kg/m2; n = 92 with PCOS, n = 64 without PCOS). Outcomes included the association between the plasma lipidomic profile (325 lipid species (24 classes) using liquid chromatography mass spectrometry) and PCOS, adiposity, homeostasis assessment of insulin resistance (HOMA), sex hormone-binding globulin (SHBG) and free androgen index (FAI). There were no associations of the lipidomic profile with PCOS or testosterone. HOMA was positively associated with 2 classes (dihydroceramide and triacylglycerol), SHBG was inversely associated with 2 classes (diacylglycerol and triacylglycerol), FAI was positively associated with 8 classes (ceramide, phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine, phosphatidylinositol, diacylglycerol and triacylglycerol) and waist circumference was associated with 8 classes (4 positively (dihydroceramide, phosphatidylglycerol, diacylglycerol and triacylglycerol) and 4 inversely (trihexosylceramide, GM3 ganglioside, alkenylphosphatidylcholine and alkylphosphatidylethanolamine)). The lipidomic profile was primarily related to central adiposity and FAI in women with or without PCOS. This supports prior findings that adiposity is a key driver of dyslipidaemia in PCOS and highlights the need for weight management through lifestyle interventions.

Circulating leptin, resistin, adiponectin, visfatin, adipsin and ghrelin levels and insulin resistance in postmenopausal women with and without the metabolic syndrome.

OBJECTIVE: To measure serum levels of adipsin, leptin, resistin, adiponectin, visfatin, ghrelin and insulin in postmenopausal women screened for the metabolic syndrome (METS). METHODS: Serum of 100 postmenopausal women was analyzed using multiplex technology for the mentioned analytes. In addition, values for the homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Comparisons were performed in accordance to the presence or not of the METS and each of its components. Criteria of the American Heart Association were used to define the METS. RESULTS: Age and time since menopause onset were similar in women with the METS (n=57) as compared to those without the syndrome (n=43). METS women displayed significantly higher levels of adipsin, leptin, resistin, insulin and HOMA-IR values and lower adiponectin levels. These differences were mainly observed among women with abdominal obesity, independent of fulfilling METS criteria or not. In this same sense, lower adiponectin levels significantly related to low HDL-C and high triglyceride levels; and higher insulin and HOMA-IR values related to high triglyceride and glucose levels, respectively. CONCLUSION: In this sample, postmenopausal women with the METS displayed higher insulin and adipokine levels. These were mainly related to abdominal obesity and metabolic and lipid abnormalities. More research is warranted in this regard.

On-line two dimensional liquid chromatography/mass spectrometry for the analysis of triacylglycerides in peanut oil and mouse tissue.

Triacylglycerides (TAGs) are a large class of complex neutral lipids that naturally occur in both plants and animals. In the present work, an on-line comprehensive silver-ion liquid chromatography (silver-ion LC) × reversed-phase liquid chromatography (RPLC) system was constructed to analyze these compounds. A micro bore silver-ion modified column was employed in the first dimension with the commonly used hexane-based mobile phase. After a series of C18 columns were assessed, a wide bore column packed with 1.5 µm particles was selected as the second dimension column to reduce the negative effect caused by the large volume and strong solvent injection in the second dimension. The system coupled with mass spectrometry was applied to the analysis of an edible peanut oil and a mouse liver extract. Twenty-eight TAGs from the peanut oil and forty-four from the mouse liver were identified based on the TAGs' retention behaviors on the comprehensive two-dimensional LC system and their APCI MS fragments.

Efecto del aceite de sacha inchi (plukenetia volúbilis l) sobre el perfil lipídico en pacientes con hiperlipoproteinemia / Effect of sacha inchi oil (plukenetia volúbilis l) on the lipid profile of patients with hyperlipoproteinemia

El presente es un trabajo experimental piloto, abierto, para conocer el efecto, dosis efectiva y efectos secundarios del aceite de sacha inchi (Plukenetia volúbilis L) en el perfil lipídico de pacientes con hipercolesterolemia; para ello, se incluyó a 24 pacientes de 35 a 75 años, en quienes se determinó los valores sanguíneos de colesterol total (CT), HDL, triglicéridos (Tg), glucosa, ácidos grasos no esterificados (AGNE) e insulina Se aleatorizó a los participantes para recibir 5 mL o 10 mL de una suspensión conteniendo 2gr/5ml de aceite de sacha inchi, durante cuatro meses. La ingesta del aceite produjo caída en los valores promedio del CT, y AGNE con elevación del c-HDL en ambos grupos. La dosis de 10 mL se asoció a mayores niveles de insulina en el grupo aleatorizado a recibir 10 ml. El aceite de sacha inchi parece tener efectos benéficos sobre el perfil lipídico en pacientes con dislipidemia, requiriéndose la evaluación de su eficacia y seguridad en ensayos clínicos aleatorizados.

We performed a pilot, experimental, open study in order to know the effect, effective dosage and secondary effects of sacha inchi´s (Plukenetia volúbilis L) oil on the lipid profiles of patients with hypercholesterolemia. We included 24 patients of ages 35 to 75, to whom we measured total cholesterol (TC), HDL, triglycerides (Tg), glucose (G), non-esterified fatty acids (NEFA) and insulin (I) levels in blood, then we randomized them to receive sacha inchi oil orally 5 ml or 10 ml of a suspension of sacha inchi oil (2gr/5ml) for four months. The oil intake produced a decrease in the mean values of TC, and NEFA, and a rise in HDL in both subgroups. The subgroup receiving 10 ml was associated to an increase in the insulin levels. Sacha inchi oil appears to have beneficial effects on the lipid profile of patients with dyslipidemia, but their efficacy and security should be evaluated in randomized clinical trials.

[Body mass index influence on aortic valve stenosis]. / Wskaznik masy ciala, a naturalny przebieg zwezenia lewego ujscia tetniczego.

AIM: The 12 months' observation of body mass index (BMI) influence on natural course of aortic valve stenosis (AVS). PATIENTS: 60 AVS patients who did not agree for operational treatment were divided into group A (n = 15) with BMI 20-25, group B (n = 27) with BMI 25,01-30 and group C BMI > 30. METHODS: Plasma Lp(a), total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor (TNF-alpha) as well as titers of immunoglobulin (Ig) class G, A, M against chlamydia pneumoniae were measured every 12 months. Echo-cardiographic evaluation of aortic valve was also done every 12 months. RESULTS: Means serum CRP at 12 month was the highest in group C. No differences in mean serum TNF-alpha and IL-6 levels as well as in Ig titers between groups A, B, C were found. At 12 month of observation HDL/total cholesterol ratio as well as HDL/LDL-cholesterol ratio were the lowest in group B. Left atrium diameter and right ventricle diameter were bigger in groups B and C compared to group A at the visit I and after 12 months of observation. Systolic intraventricular septum (IVS syst) thickness was the highest in group C at visit I. Diastolic left ventricle posterior wall thickness (LVPW) was the highest in group C during 12 months of observation. CONCLUSION: The increase in fat tissue mass may lead to increase in inflammatory process and cardiac muscle remodeling in AVS patients.

[Effect of sacha inchi oil (plukenetia volúbilis l) on the lipid profile of patients with hyperlipoproteinemia]. / Efecto del aceite de sacha inchi (plukenetia volúbilis l) sobre el perfil lipídico en pacientes con hiperlipoproteinemia.

We performed a pilot, experimental, open study in order to know the effect, effective dosage and secondary effects of sacha inchi´s (Plukenetia Huallabamba) [corrected] oil on the lipid profiles of patients with hypercholesterolemia. We included 24 patients of ages 35 to 75, to whom we measured total cholesterol (TC), HDL, triglycerides (Tg), glucose (G), non-esterified fatty acids (NEFA) and insulin (I) levels in blood, then we randomized them to receive sacha inchi oil orally 5 ml or 10 ml of a suspension of sacha inchi oil (2gr/5ml) for four months. The oil intake produced a decrease in the mean values of TC, and NEFA, and a rise in HDL in both subgroups. The subgroup receiving 10 ml was associated to an increase in the insulin levels. Sacha inchi oil appears to have beneficial effects on the lipid profile of patients with dyslipidemia, but their efficacy and security should be evaluated in randomized clinical trials.

A 24-month dietary carcinogenicity study of DAG in mice.

This study evaluated the possible carcinogenic effects of DAG (diacylglycerol) oil when given in the diet at levels up to 6.0% for 24 months to mice. Dietary fat was provided by DAG and/or the control article, TG (triacylglycerol oil). Dietary concentrations (% DAG/% TG) were 0%/6.0% (TG control), 1.5%/4.5%, 3.0%/3.0%, and 6.0%/0%. An additional control group received the standard rodent diet (fat content 4.5%). The clinical condition of the animals, ophthalmic findings, palpable mass occurrence, body weights and gross and histopathologic findings were unaffected by DAG in comparison to TG. The findings in DAG-treated groups were no different than those observed in the TG control group. The standard basal diet had 4.5% fat content. Both TG and/or DAG, when presented separately or together in the diet at a total fat level of 6.0%, resulted in some differences relative to the basal diet control (lower survival, higher body weights, lower food consumption, and higher incidences of macroscopic and microscopic findings), presumably related to the higher dietary fat content and/or the semi-purified diet. However, these parameters were similar in groups fed a diet with 6.0% dietary fat that was either DAG or TG. Thus, DAG at dietary concentrations up to 6.0% for 24 months produced no signs of systemic toxicity and had no effect on the incidence of neoplastic findings.

A 24-month dietary carcinogenicity study of DAG (diacylglycerol) in rats.

Toxicologic and carcinogenic effects of DAG (diacylglycerol) oil, administered in diet for 24 months to Crl:CD((R))(SD)-IGS BR rats, were evaluated using diet-restricted and ad libitum-fed groups. All dietary fat (consistently 5.5%) was provided by DAG and/or the control article, TG (triacylglycerol) oil. Dietary concentrations (% DAG/% TG) were 0%/5.5%, 1%/4.5%, 2.75%/2.75% and 5.5%/0%. Separate groups were fed the 0%/5.5% and 5.5%/0% diets ad libitum. Another group received the standard rodent diet (fat content 4.5%) on the restricted feeding regimen. Clinical condition, ophthalmic findings, palpable mass occurrence, body composition, clinical pathology parameters and incidence of neoplastic lesions were unaffected by DAG in comparison to TG. Groups fed the 5.5% (DAG and/or TG) fat diet when compared to the 4.5% fat diet group displayed lower survival, higher body weights, organ weights, percent body fat, higher fat-related serum chemistry parameters, incidence of microscopic changes in the heart, kidneys, liver, bone marrow, spleen, and incidences of pituitary and mammary gland neoplasms. Parameters more affected in all the ad libitum groups than in the restricted diet groups (regardless of test article) fed the same diet included survival, body weights, body fat, fat-related serum chemistry parameters, and incidences of heart, kidney and liver microscopic changes. However, the DAG and TG ad libitum-fed groups were not different from one another. Thus, DAG-treated animals had no higher risk of carcinogenic effects than rats fed on similar feeding regimens with a diet in which all dietary fat came from TG.

Triglyceride and coronary heart disease mortality in a 24-year follow-up study in Xi'an, China.

PURPOSE: To study whether serum triglyceride (TG) was associated with coronary heart disease (CHD) mortality. METHODS: A cohort analytic study carried out in a machinery factory in Xi'an, China on 1696 subjects aged 35 years or above (1124 men and 572 women) examined in 1976 and followed up till 2000. RESULTS: At baseline, the mean serum total cholesterol (TC) and triglyceride (TG) was 4.64 and 1.16 mmol/L in men, 4.62 and 1.10 mmol/L in women, respectively. Three hundred six (239 men, 67 women) had died within 37,781 person-years of follow-up, with 49 CHD deaths (36 male, 13 female). The relative risk (95% confidence interval) of CHD mortality per mmol/L increase in TG was 2.13 (1.46-3.17) after adjusting for age, marital status, occupation, education, systolic blood pressure and TC. Dose-response relationship between TG levels by tertiles and CHD risk was found. Stratified analyses showed TG was an independent predictor for CHD mortality in subjects with lower or higher TC. CONCLUSIONS: Chinese had lower levels of TC and TG than Western populations. This study provides new evidence that TG is an independent risk factor of CHD in subjects with lower or higher TC levels, and supports the lowering of cut-off value for elevated triglyceride.