Decreased Plasma Triglyceride Research Articles

Effect of Ocimum sanctum (Basil) leaf in high-fat-diet induced hyperlipidemic rat

Dyslipidemia mediated atherosclerosis is the key pathogenesis of several cardiovascular diseases. Present study aimed to evaluate the therapeutic potential of Ocimum sanctum leaf consumption against high-fat-diet induced hyperlipidemia in rat model. A total of 18 Wistar albino rats (200-215 g) were randomly divided as control, HFD (hyperlipidemic) and OS-treated groups. HFD-group received high fat diet (HFD) for 15 days, OS-treated group administered with Ocimum sanctum leaf powder (200 mg / kg of bodyweight / day) together with HFD diet for 15 days. Blood samples were analyzed for changes in plasma total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein and very-low-density lipoprotein. Plasma atherogenic index was also calculated. HFD administration significantly increase plasma lipid levels and atherogenic index in HFD-group. Ocimum sanctum supplementation significantly reduce decrease plasma total cholesterol, triglyceride, lipoproteins and atherogenic index in OS-treated rats. 15 days Ocimum sanctum leaf (powder) supplementation at dose of 200 mg / kg of bodyweight / day effectively attenuates dyslipidemia in hyperlipidemic rats.

Antihyperglycemic and antihyperlipidemic activities of hydroethanolic extract of the fruit of Baillonella toxisperma in streptozotocin-induced diabetic rats

ObjectiveThis work evaluated the antihyperglycemic and antihyperlipidemic activities of pulp extracts of B. toxisperma fruits in rats. MethodsThe regulatory ability of the extract on the secretory capacity of pancreatic beta cells (oral glucose tolerance test), and digestion and/or absorption of carbohydrates (starch and sucrose) were evaluated on normal Wistar rats. Diabetes was induced in Wistar rats by intravenous administration of streptozotocin (50 mg/kg), and the animals were treated by the administration of a single daily dose of 400 mg/kg BW of extract. The effect of the extract on blood glucose levels of diabetic rats was monitored 30 min, 2 h, and 5 h after administration, and on the 7th and 14th days of treatment. After 2 weeks of treatment, the rats were sacrificed, liver was preserved for the determination of glycogen content. The serum was prepared and markers for nephro and hepatotoxicity were assessed, as well as cardiovascular risk. ResultsThe hydroethanolic extract of B. toxisperma fruits significantly reduced glucose concentrations after administration of starch and sucrose in normoglycemic rats by limiting the glycemic peak (increasing of 19.67% vs 27.88% for positive control and 35.96% vs 43.97% for positive control, for starch and sucrose respectively). No effect was observed after glucose administration. B. toxisperma fruits significantly decreased glucose levels by 14.5% and 54.23% respectively 30 min after administration and 7th days of treatment respectively. The extract decreased plasma triglycerides and total cholesterol levels in diabetic rats; it also decreased the cardiovascular risk through the reduction of Cardiac Risk Ratio, Atherogenic Coefficient, and non-High-Density Lipoprotein Cholesterol. The extract also promoted renal function but not structural integrity of the liver. ConclusionsThis study suggests that the hydroethanolic pulp extracts of B. toxisperma fruits are good antihyperglycemic and antihyperlipidemic properties agents and could be a potential source of compounds for diabetes management.

Phosphatidylcholine (18:0/20:4), a potential biomarker to predict ethionamide-induced hepatic steatosis in rats.

Ethionamide (ETH), a second‐line drug for multidrug‐resistant tuberculosis, is known to cause hepatic steatosis in rats and humans. To investigate predictive biomarkers for ETH‐induced steatosis, we performed lipidomics analysis using plasma and liver samples collected from rats treated orally with ETH at 30 and 100 mg/kg for 14 days. The ETH‐treated rats developed hepatic steatosis with Oil Red O staining‐positive vacuolation in the centrilobular hepatocytes accompanied by increased hepatic contents of triglycerides (TG) and decreased plasma TG and total cholesterol levels. A multivariate analysis for lipid profiles revealed differences in each of the 35 lipid species in the plasma and liver between the control and the ETH‐treated rats. Of those lipids, phosphatidylcholine (PC) (18:0/20:4) decreased dose‐dependently in both the plasma and liver. Moreover, serum TG‐rich very low‐density lipoprotein (VLDL) levels, especially the large particle fraction of VLDL composed of PC containing arachidonic acid (20:4) involved in hepatic secretion of TG, were decreased dose‐dependently. In conclusion, the decreased PC (18:0/20:4) in the liver, possibly leading to suppression of hepatic TG secretion, was considered to be involved in the pathogenesis of the ETH‐induced hepatic steatosis. Therefore, plasma PC (18:0/20:4) levels are proposed as mechanism‐related biomarkers for ETH‐induced hepatic steatosis.

Dietary protein/carbohydrate ratio and feeding frequency affect feed utilization, intermediary metabolism, and economic efficiency of gilthead seabream (Sparus aurata) juveniles

To evaluate the effects of dietary protein/carbohydrate (P/CHO) ratio and feeding frequency (FF) on growth, intermediary metabolism, and economic efficiency of gilthead seabream (Sparus aurata) juveniles, two practical isolipidic (17%) diets were formulated to include high protein (50%)/ low starch (10%) (diet P50/CHO10) or low protein (40%)/ high starch (20%) (diet P40/CHO20). Triplicate groups of fish with 9.1 ± 0.01 g were fed for 60 days with these diets until visual satiation at three FF: one (9:00), two (9:00 and 17:00), or three (9:00, 13:00, and 17:00) meals per day. Dietary P/CHO ratios did not affect growth performance while feeding 2 or 3 meals per day improved fish growth. Fish fed diet P40/CHO20 had increased feed intake (FI), protein efficiency ratio (PER), and nitrogen retention (NR), and lower feed efficiency (FE), nitrogen intake (NI), and economic conversion ratio (ECR). Feeding 2 or 3 meals per day increased FI, NI, ECR, and economic profit index, and decreased FE, PER, and NR. Fish fed diet P40/CHO20 presented increased hepatic lipid and glycogen content, hepatocyte area covered by lipid vacuoles, and glucokinase (gk) gene expression, and decreased glutamate dehydrogenase expression. Fish fed 3 meals per day had decreased plasma triglycerides and total protein levels, while fish fed 2 or 3 meals per day presented decreased hepatic growth hormone receptor-i (ghr-i), gk, and fatty acid synthase gene expression. Interaction between P/CHO ratio and FF was only observed in plasmatic glucose, cholesterol, and total lipids levels, and insulin-like growth factor-1, and ghr-ii gene expression. Overall, glycogenesis, glycolysis, and economic efficiency seemed to be increased while the amino acid catabolism was reduced in fish fed the P40/CHO20 diet. Higher FF increased growth and economic efficiency, and reduced glycolysis and lipogenesis pathways. In conclusion, a diet with P40/CHO20 ratio fed twice a day appears to be the most adequate strategy regarding feed utilization and economic efficiency for gilthead seabream juveniles in order to achieve optimum sustainable aquaculture.

Effect of Parathyroidectomy on Metabolic Homeostasis in Primary Hyperparathyroidism.

Background: The benefits of parathyroidectomy on cardiovascular risk in primary hyperparathyroidism (PHPT) are controversial. This monocentric, observational, prospective study aimed to assess the effects of parathyroidectomy on glucose and lipid metabolism in classic or mild PHPT. Methods: Patients who underwent parathyroidectomy for classic (calcemia >2.85 mmol/L) or mild PHPT (calcemia ≤2.85 mmol/L) between 2016 and 2019 were included. A metabolic assessment was performed before and 1 year after parathyroidectomy. Patients with a history of diabetes were excluded. Results: Nineteen patients had classic and 120 had mild PHPT. Ninety-five percent were normocalcemic 6 months after surgery. Fasting plasma glucose and insulin levels decreased after parathyroidectomy in patients with mild PHPT (p < 0.001). HOMA-IR decreased after surgery in the overall population (p < 0.001), while plasma adiponectin concentrations increased in patients with both classic (p = 0.005) and mild PHPT (p < 0.001). Plasma triglyceride levels decreased significantly only in patients with classic PHPT (p = 0.021). Plasma PCSK9 levels decreased in patients with mild PHPT (p < 0.001). Conclusions: Parathyroidectomy for PHPT improves insulin resistance and decreases plasma triglyceride levels in classic PHPT and plasma PCSK9 levels in mild PHPT. Further studies are needed to better characterize the consequences of such metabolic risk factors’ improvements on cardiovascular events.

Both low-fat and low-carbohydrate diets reduce triglyceride concentration in subjects with multifactorial chylomicronemia syndrome: a randomized crossover study

Multifactorial chylomicronemia syndrome (MCS) is a complex disease including a genetic component and the presence of lifestyle-related risk factors. We hypothesized that, in subjects with MCS, there would be a greater decrease in plasma triglycerides (TG) with a low-fat (F) diet than with a low-carbohydrate (C) diet. In secondary analyses, we tested the effect of both diets on TG concentration according to the presence or absence of a rare variant in the LPL gene. This randomized crossover dietary intervention included 12 adult subjects with MCS. Subjects followed 2 isocaloric diets, low-C (C, 35%; F, 45%) and low-F (F, 20%; C, 60%), in random order. Each diet lasted 3 weeks, followed by a 6-hour test meal. Diets were separated by a 2-week washout period. TG concentration in fasting subjects decreased by 55% during low-F diet (P = .002) and by 48% during low-C diet (P = .005). The difference between the 2 diets was not significant. However, we observed a more pronounced decrease in TG concentration (65% ± 17%) with the low-F diet compared with the low-C diet (46% ± 31%) (P=.06) in subjects carrying a rare variant in the LPL gene. This is the first study to show that dietary intervention is effective in MCS subjects. In addition, we highlighted the importance of the genetic profile in the choice of treatment by suggesting that subjects with a rare variant of the LPL gene have a greater reduction of TG concentration with a low-F diet than with a low-C diet.

CREBH regulation of lipid metabolism through multifaceted functions that improve arteriosclerosis.

Cyclic adenosine monophosphate-responsive element-binding protein H (CREBH) activates lipoprotein lipase (LPL) activity by modulating apolipoproteins. Activated LPL hydrolyzes triglyceride-rich lipoproteins, such as very low-density lipoprotein (VLDL) and chylomicrons, resulting in remnant lipoproteins. CREBH increases apolipoprotein E (ApoE), a ligand that mediates the clearance of remnant particles and reduces ApoC3, which interferes with remnant clearance. CREBH also improves VLDL receptor (VLDLR) and LDL receptor-related protein 1 (LRP1) protein that mediates remnant clearance. Therefore, CREBH promotes the clearance of remnant particles from the blood, decreasing the atherogenic plaque area. CREBH induces the secretion of fibroblast growth factor 21 (FGF21) into the blood, decreasing plasma triglyceride. CREBH produces ApoA1 and so increases plasma HDL-cholesterol levels.

Lentinan Protects against Nonalcoholic Fatty Liver Disease by Reducing Oxidative Stress and Apoptosis via the PPARα Pathway.

Lentinan (LNT), a type of polysaccharide derived from Lentinus edodes, has manifested protective effects during liver injury and hepatocellular carcinoma, but little is known about its effects on nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate whether LNT can affect the progression of NAFLD and the associated mechanisms. C57BL/6J mice were fed a normal chow diet or a high-fat diet (HFD) with or without LNT (6 mg/kg/d). AML12 cells were exposed to 200 μM palmitate acid (PA) with or without LNT (5 μg/mL). After 21 wk of the high-fat diet, LNT significantly decreased plasma triglyceride levels and liver lipid accumulation, reduced excessive reactive oxygen species production, and subsequently attenuated hepatic apoptosis in NAFLD mice. These effects were associated with increased PPARα levels, a decreased Bax/Bcl-2 ratio, and enhancement of the antioxidant defense system in vivo. Similar effects were also observed in cultured cells. More importantly, these protective effects of LNT on palmitate acid-treated AML12 cells were almost abolished by PPARα knockdown. In conclusion, this study demonstrates that LNT may ameliorate hepatic steatosis and decrease oxidative stress and apoptosis by activating the PPARα pathway and is a potential drug target for NAFLD.

The Effects of PPAR Agonists on Atherosclerosis and Nonalcoholic Fatty Liver Disease in ApoE-/-FXR-/- Mice.

Background Farnesoid X receptor (FXR), a bile acid–activated nuclear receptor, is a potent regulator of glucose and lipid metabolism as well as of bile acid metabolism. Previous studies have demonstrated that FXR deficiency is associated with metabolic derangements, including atherosclerosis and nonalcoholic fatty liver disease (NAFLD), but its mechanism remains unclear. In this study, we investigated the role of FXR in atherosclerosis and NAFLD and the effect of peroxisome proliferator-activated receptor (PPAR) agonists in mouse models with FXR deficiency.Methods En face lipid accumulation analysis, liver histology, serum levels of glucose and lipids, and mRNA expression of genes related to lipid metabolism were compared between apolipoprotein E (ApoE)−/− and ApoE−/−FXR−/− mice. The effects of PPARα and PPARγ agonists were also compared in both groups of mice.Results Compared with ApoE−/− mice, ApoE−/−FXR−/− mice showed more severe atherosclerosis, hepatic steatosis, and higher levels of serum cholesterol, low-density lipoprotein cholesterol, and triglycerides, accompanied by increased mRNA expression of FAS, ApoC2, TNFα, IL-6 (liver), ATGL, TGH, HSL, and MGL (adipocytes), and decreased mRNA expressions of CPT2 (liver) and Tfam (skeletal muscle). Treatment with a PPARα agonist, but not with a PPARγ agonist, partly reversed atherosclerosis and hepatic steatosis, and decreased plasma triglyceride levels in the ApoE−/−FXR−/− mice, in association with increased mRNA expression of CD36 and FATP and decreased expression of ApoC2 and ApoC3 (liver).Conclusion Loss of FXR is associated with aggravation of atherosclerosis and hepatic steatosis in ApoE-deficient mice, which could be reversed by a PPARα agonist through induction of fatty acid uptake, β-oxidation, and triglyceride hydrolysis.

Structural simplification and bioisostere principle lead to Bis-benzodioxole-fibrate derivatives as potential hypolipidemic and hepatoprotective agents

The bis-benzodioxole-fibrate hybrids were designed by structural simplification and bioisostere principle. Lipids lowering activity was preliminarily screened by Triton WR 1339 induced hyperlipidemia mice model, in which T3 showed the best hypolipidemia, decreasing plasma triglyceride (TG) and total cholesterol (TC), which were better than sesamin and fenofibrate (FF). T3 was also found to significantly reduce TG, TC and low density lipoprotein cholesterin (LDL-C) both in plasma and liver tissue of high fat diet (HFD) induced hyperlipidemic mice. In addition, T3 showed hepatoprotective activity, which the noteworthy amelioration in liver aminotransferases (AST and ALT) was evaluated and the histopathological observation exhibited that T3 inhibited lipids accumulation in the hepatic and alleviated liver damage. The expression of PPAR-α receptor involved lipids metabolism in liver tissue significantly increased after T3 supplementation. Other potent activity, such as antioxidation and anti-inflammation, was also observed. The molecular docking study revealed that T3 has good affinity activity toward to the active site of PPAR-α receptor. Based on these findings, T3 may serve as an effective hypolipidemic agent with hepatoprotection.

Browning of White Adipose Tissue as a Therapeutic Tool in the Fight against Atherosclerosis.

Despite continuous medical advances, atherosclerosis remains the prime cause of mortality worldwide. Emerging findings on brown and beige adipocytes highlighted that these fat cells share the specific ability of non-shivering thermogenesis due to the expression of uncoupling protein 1. Brown fat is established during embryogenesis, and beige cells emerge from white adipose tissue exposed to specific stimuli like cold exposure into a process called browning. The consecutive energy expenditure of both thermogenic adipose tissues has shown therapeutic potential in metabolic disorders like obesity and diabetes. The latest data suggest promising effects on atherosclerosis development as well. Upon cold exposure, mice and humans have a physiological increase in brown adipose tissue activation and browning of white adipocytes is promoted. The use of drugs like β3-adrenergic agonists in murine models induces similar effects. With respect to atheroprotection, thermogenic adipose tissue activation has beneficial outcomes in mice by decreasing plasma triglycerides, total cholesterol and low-density lipoproteins, by increasing high-density lipoproteins, and by inducing secretion of atheroprotective adipokines. Atheroprotective effects involve an unaffected hepatic clearance. Latest clinical data tend to find thinner atherosclerotic lesions in patients with higher brown adipose tissue activity. Strategies for preserving healthy arteries are a major concern for public health.

Effects of KY-903, a Novel Tetrazole-Based Peroxisome Proliferator-Activated Receptor γ Modulator, in Male Diabetic Mice and Female Ovariectomized Rats.

Peroxisome proliferator-activated receptor γ (PPARγ) modulators are expected to exert anti-diabetic effects without PPARγ-related adverse effects, such as fluid retention, weight gain, and bone loss. The present study showed that the novel tetrazole derivative KY-903 exerted similar selective PPARγ partial agonist properties to INT-131, a known PPARγ modulator, in transactivation assays, and decreased plasma glucose and triglyceride levels with increases in adiponectin levels in diabetic KK-Ay mice. These effects were similar to those of pioglitazone. Pioglitazone, but not KY-903, increased adipose tissue and heart weights. In pre-adipocytes (3T3-L1), KY-903, in contrast to pioglitazone, increased adiponectin mRNA levels without adipocyte differentiation, indicating anti-diabetic effects via adiponectin without adipogenesis. In ovariectomized rats fed a high-fat diet (OVX/HFD), KY-903 and pioglitazone decreased plasma triglyceride and non-esterified fatty acid levels and increased adiponectin levels, indicating insulin sensitization via adiponectin. KY-903 reduced body weight gain and adipose tissue weight, while pioglitazone increased heart weight and markedly reduced bone mineral density. In mesenchymal stem cell-like ST2 cells, KY-903 slightly reduced osteoblast differentiation without adipocyte differentiation, while pioglitazone markedly reduced it with adipocyte differentiation. In conclusion, KY-903 is a novel PPARγ modulator that exerts anti-diabetic effects without body weight gain or cardiac hypertrophy in diabetic mice and anti-obesity effects with minor bone loss in OVX/HFD, possibly due to increases in adiponectin levels without adipogenesis.

Carrot Supplementation Improves Blood Pressure and Reduces Aortic Root Lesions in an Atherosclerosis-Prone Genetic Mouse Model.

Epidemiological studies have shown that carrot consumption may be associated with a lower risk of developing several metabolic dysfunctions. Our group previously determined that the Bolero (Bo) carrot variety exhibited vascular and hepatic tropism using cellular models of cardiometabolic diseases. The present study evaluated the potential metabolic and cardiovascular protective effect of Bo, grown under two conditions (standard and biotic stress conditions (BoBS)), in apolipoprotein E-knockout (ApoE−/−) mice fed with high fat diet (HFD). Effects on metabolic/hemodynamic parameters and on atherosclerotic lesions have been assessed. Both Bo and BoBS decreased plasma triglyceride and expression levels of genes implicated in hepatic de novo lipogenesis and lipid oxidation. BoBS supplementation decreased body weight gain, secretion of very-low-density lipoprotein, and increased cecal propionate content. Interestingly, Bo and BoBS supplementation improved hemodynamic parameters by decreasing systolic, diastolic, and mean blood pressure. Moreover, Bo improved cardiac output. Finally, Bo and BoBS substantially reduced the aortic root lesion area. These results showed that Bo and BoBS enriched diets corrected most of the metabolic and cardiovascular disorders in an atherosclerosis-prone genetic mouse model and may therefore represent an interesting nutritional approach for the prevention of cardiovascular diseases.

Effects of Fermented Beverage in Subjects with Metabolic Syndrome.

This study investigated the effects of fermented beverage, kale/apple juice containing 5% vinegar in subjects with metabolic syndrome. Subjects were randomly assigned to receive 250 mL fermented beverage or water containing fructose, glucose, and sucrose twice daily for 10 weeks. Consumption of the fermented beverage significantly decreased plasma triglyceride, thiobarbituric acid reactive substances (TBARS), tumor necrosis factor (TNF)-α, and high sensitivity C-reactive protein (hs-CRP) levels compared to baseline values (P<0.05). Furthermore, consumption of the fermented beverage significantly decreased homeostasis model assessment for insulin resistance (HOMA-IR) values and atherogenic indexes compared with baseline values (P<0.05). In the control group, plasma triglyceride, TBARS, TNF-α, and hs-CRP levels, atherogenic indexes, and HOMA-IR values did not significantly differ pre-and post-treatment. The fermented beverage inhibited the activities of α-glucosidase and pancreatic lipase in vitro, therefore could be helpful in alleviating metabolic syndrome in subjects with metabolic syndrome.

SIRT1/NFκB pathway mediates anti-inflammatory and anti-apoptotic effects of rosmarinic acid on in a mouse model of nonalcoholic steatohepatitis (NASH)

Nonalcoholic steatohepatitis (NASH) is considered as a common liver disease. SIRT1, a pivotal sensor, controls activation of metabolic, inflammatory and apoptotic pathways. Rosmarinic acid (RA) has positive effects on the liver injuries; nevertheless, its mechanisms are not completely studied. The aim of this study was to explore the role of rosmarinic acid on the pathways involved by SIRT1 for amelioration of a mouse model of NASH. To do this, C57/BL6 mice were divided into four equal groups (6 in each group). Animals received saline and rosmarinic acid as the control groups. NASH was induced by methionine-choline-deficient (MCD) diet. In the NASH + RA group, Rosmarinic acid was injected daily in mice fed on an MCD diet. Rosmarinic acid decreased plasma triglyceride, cholesterol, liver Steatosis and oxidative stress. Rosmarinic acid administration also increased SIRT1, Nrf2 and PPARα and decreased SREBP1c, FAS, NFκB and caspase3 expressions. Moreover, TNFα, IL6, P53, Bax/Bcl2 ratio and caspase3 expressions decreased. Our study demonstrated that remarkable effects of rosmarinic acid on the mice with NASH might be due to activation of SIRT1/Nrf2, SIRT1/NFκB and SIRT1/PPARα pathways, which alleviate hepatic steatosis, oxidative stress, inflammation and apoptosis.

The attenuation of postprandial lipemia by aerobic exercise depends on allelic variations of the Apolipoprotein B gene

To investigate the effect of aerobic exercise on postprandial lipemia (PPL) related to allelic variants of the apolipoprotein B ( APOB ) gene. All volunteers participated in three randomly selected trials, with at least 48 h between sessions: control (no exercise), MOD-EX (moderate exercise) and INT-EX (intense exercise). Two groups of healthy young men composed of 11 and 19 carriers of the C/C and T/C genotypes of the APOB gene (rs693) were constituted. Each exercise test (MOD-EX and INT-EX) were done until the 500-kcal expenditure and were completed 30-min before ingestion of a high-fat meal (HFM). Venous blood was collected before the exercise test and at 1, 2, 3 and 4 h after the HFM. PPL was assessed using the area under the curve approach as well as the kinetic profile of mean lipid variables. Statistical significance was adopted at P < 0.05 level. The C/C group exhibited a decrease in plasma triglycerides, total cholesterol and very low-density lipoprotein levels following both MOD-EX (1378 ± 787 vs 1069 ± 537; 837 ± 122 vs 830 ± 150; 206 ± 78 vs 186 ± 59, respectively) and INT-EX (1378 ± 787 vs 1119 ± 526; 837 ± 122 vs 828 ± 151; 206 ± 78 vs 174 ± 93, respectively). Interestingly, the T/C group was insensitive to any of the attempts to reduce circulating fat. Moderate and intense aerobic exercise were both equally effective in attenuating PPL in the C/C carriers of the APOB gene. Étudier l’effet de l’exercice aérobie sur la lipémie postprandiale (PPL) liée aux variantes alléliques du gène de l’apolipoprotéine B (APOB). Tous les volontaires ont participé à trois essais sélectionnés au hasard, avec au moins 48 h entre les sessions: contrôle (pas d’exercice), MOD-EX (exercice modéré) et INT-EX (exercice intense). Deux groupes de jeunes hommes en bonne santé composés de 11 et 19 porteurs des génotypes C/C et T/C du gène APOB (rs693) ont été constitués. Chaque test d’effort (MOD-EX et INT-EX) a été effectué jusqu’à la dépense de 500 kcal et a été achevé 30 min avant l’ingestion d’un repas riche en graisses (HFM). Le sang veineux a été prélevé avant l’épreuve d’effort et 1, 2, 3 et 4 h après la HFM. La PPL a été évaluée en utilisant l’aire sous l’approche de la courbe ainsi que le profil cinétique des variables lipidiques moyennes. La signification statistique a été adoptée au niveau p < 0,05. Le groupe C/C a montré une diminution des triglycérides plasmatiques, du cholestérol total et des taux de lipoprotéines de très basse densité après les deux MOD-EX (1378 ± 787 vs 1069 ± 537 ; 837 ± 122 vs 830 ± 150; 206 ± 78 vs 186 ± 59, respectivement) et INT-EX (1378 ± 787 contre 1119 ± 526; 837 ± 122 contre 828 ± 151; 206 ± 78 contre 174 ± 93, respectivement). Fait intéressant, le groupe T/C était insensible à toutes les tentatives de réduction des graisses en circulation. L’exercice aérobie modéré et intense étaient tous deux également efficaces pour atténuer la PPL dans les porteurs C/C du gène APOB .

Empagliflozin increases plasma levels of campesterol, a marker of cholesterol absorption, in patients with type 2 diabetes: Association with a slight increase in high-density lipoprotein cholesterol

Background and aimsSodium/glucose cotransporter 2 (SGLT2) inhibitors decrease plasma triglyceride levels and slightly increase low-density lipoprotein (LDL-c) and high-density lipoprotein cholesterol (HDL-c). However, the mechanisms underlying such changes in the blood lipid profile remain to be determined. We investigated how empagliflozin affects plasma markers of cholesterol absorption and synthesis, and evaluated the relationship between changes in these markers and blood lipids in patients with type 2 diabetes. Methods and resultsIn a randomized, active-controlled, open-label trial, 51 patients were randomly allocated in 2:1 ratio to receive empagliflozin 10 mg/day (n = 32) or standard therapy (n = 19) for 12 weeks. We measured plasma levels of lathosterol as a marker of cholesterol synthesis, and campesterol and sitosterol as markers of cholesterol absorption, at baseline and 12 weeks after treatment.In the empagliflozin group, serum HDL-c, but not LDL-c, significantly increased between baseline and 12 weeks (54.4 ± 16.3 vs. 58.8 ± 19.6 mg/dl; p = 0.0006), whereas in the standard therapy group, HDL-c and LDL-c remained unchanged. In the empagliflozin group, plasma campesterol also increased significantly (4.14 ± 1.88 vs. 4.90 ± 2.26 μg/ml, p = 0.0008), whereas no change in plasma campesterol or sitosterol was found in the control group. Although plasma lathosterol showed no change in the whole empagliflozin group, it decreased significantly in patients who were not taking statins. In statin non-users, plasma lathosterol decreased significantly after treatment with empagliflozin (2.71 ± 0.99 vs. 1.91 ± 0.99 μg/ml, p < 0.05). In the empagliflozin group, changes in plasma campesterol correlated positively with changes in HDL-c. ConclusionEmpagliflozin increases serum campesterol, a marker of cholesterol absorption, in patients with type 2 diabetes. This increase may be associated with SGLT2 inhibitor-induced increases in HDL cholesterol.

Effect of liver total sphingomyelin synthase deficiency on plasma lipid metabolism

Sphingomyelin (SM) is one major phospholipids on lipoproteins. It is enriched on apolipoprotein B-containing particles, including very low-density lipoprotein (VLDL) and its catabolites, low-density lipoprotein (LDL). SM is synthesized by sphingomyelin synthase 1 and 2 (SMS1 and SMS2) which utilizes ceramide and phosphatidylcholine, as two substrates, to produce SM and diacylglyceride. SMS1 and SMS2 activities are co-expressed in all tested tissues, including the liver where VLDL is produced. Thus, neither Sms1 gene knockout (KO) nor Sms2 KO approach is sufficient to evaluate the effect of SMS on VLDL metabolism. We prepared liver-specific Sms1 KO/global Sms2 KO mice to evaluate the effect of hepatocyte SM biosynthesis in lipoprotein metabolism. We found that hepatocyte total SMS depletion significantly reduces cellular sphingomyelin levels. Also, we found that the deficiency induces cellular glycosphingolipid levels which is specifically related with SMS1 but not SMS2 deficiency. To our surprise, hepatocyte total SMS deficiency has marginal effect on hepatocyte ceramide, diacylglyceride, and phosphatidylcholine levels. Importantly, total SMS deficiency decreases plasma triglyceride but not apoB levels and reduces larger VLDL concentration. The reduction of triglyceride levels also was observed when the animals were on a high fat diet. Our results show that hepatocyte total SMS blocking can reduce VLDL-triglyceride production and plasma triglyceride levels. This phenomenon could be related with a reduction of atherogenicity.

Quercetin Reverses Cardiac Systolic Dysfunction in Mice Fed with a High-Fat Diet: Role of Angiogenesis.

Global consumption of high-fat diets (HFD) is associated with an increased incidence of cardiometabolic syndrome and cardiac injury, warranting identification of cardioprotective strategies. Cardioprotective effects of quercetin (Q) have mostly been evaluated in ischemic heart disease models and attributed to senolysis. We hypothesized that Q could alleviate murine cardiac damage caused by HFD by restoring the myocardial microcirculation. C57BL/6J mice were fed standard chow or HFD for 6 months and then treated with Q (50 mg/kg) or vehicle 5-day biweekly for 10 additional weeks. Left ventricular (LV) cardiac function was studied in vivo using magnetic resonance imaging, and intramyocardial fat deposition, microvascular density, oxidative stress, and senescence were analyzed ex vivo. Additionally, direct angiogenic effects of Q were studied in vitro in HUVECs. HFD increased body weight, heart weight, total cholesterol, and triglyceride levels, whereas Q normalized heart weight and triglycerides. LV ejection fraction was lower in HFD vs. control mice (56.20 ± 15.8% vs. 73.38 ± 5.04%, respectively, P < 0.05), but improved in HFD + Q mice (67.42 ± 7.50%, P < 0.05, vs. HFD). Q also prevented cardiac fat accumulation and reduced HFD-induced cardiac fibrosis, cardiomyocyte hypertrophy, oxidative stress, and vascular rarefaction. Cardiac senescence was not observed in any group. In vitro, ox-LDL reduced HUVEC tube formation activity, which Q effectively improved. Quercetin may directly induce angiogenesis and decrease myocardial oxidative stress, which might account for its cardioprotective effects in the murine HFD-fed murine heart independently from senolytic activity. Furthermore, its beneficial effects might be partly attributed to a decrease in plasma triglycerides and intramyocardial fat deposition.

The Effect of Supplementing Tea Polyphenols in Diet of Laying Hens on Yolk Cholesterol Content and Production Performance

ABSTRACT This study was conducted to evaluate the influence of supplementing tea polyphenols (TP) in diet of laying hens on yolk cholesterol content and production performance. A total of 1800 Lohmann laying hens aged 48 weeks were randomly allocated to 6 groups. Each group consisted of 6 replicates with 50 layers. The feeding experiment was 4 weeks including one-week acclimatization. Layers fed basal diet supplemented with 0, 150, 200, 250, 300 and 350 mg TP/kg diet, respectively. The results showed that average daily feed intake (ADFI), feed conversion ratio (FCR), average egg weight (AEW), laying rate and the indicators of egg quality were not significantly affected by the diet supplemented with 300 mg/kg TP (p>0.05). However, yolk cholesterol content decreased by increasing TP concentration (p<0.01), with 18.06% reduction in layers fed diet supplemented with 300 mg TP/kg. Also, the diet supplemented with 300 mg/kg TP significantly decreased plasma triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) level (p<0.05). The activity of serum glutathione peroxidase (GSH-Px) was enhanced by increasing TP concentration, while the content of serum methane dicarboxylic aldehyde (MDA) was decreased by increasing TP concentration. The highest activity of GSH-Px and the lowest serum MDA content were both determined in 300 mg/kg TP group (p<0.01). In conclusion, this study suggests that the addition of 300 mg TP/kg basal diet had no negative effect on the production performance laying hens, yet decreased the egg yolk cholesterol content and enhanced the antioxidant capacity of laying hens at the same time.