Interest of fasting in the exploration of the lipid balance

Introduction. Le bilan lipidique correspond à un ensemble d’analyses permettant de mettre en évidence des anomalies du métabolisme des lipides et d’optimiser la prise en charge diététique et/ou le besoin thérapeutique pour le suivi, la surveillance et l’évaluation du risque athérogène. L’objectif de cette étude est d’évaluer la place du jeûne dans les recommandations pré analytiques du dosage des paramètres lipidiques. Matériels et Méthodes. Notre étude prospective a été réalisée sur 27 prélèvements sanguins sur tube hépariné, des patients en deux temps : à jeun et non à jeun après la prise d’un repas consistant. Le dosage des deux paramètres : Triglycérides et le Cholestérol total, ont été réalisé par la méthode colorimétrique enzymatique. Résultats. Nos résultats ont été classés en deux groupes pour chaque paramètre. L’étude statistique a été réalisée sur le logiciel Graph Pad Prism7. La comparaison des deux groupes TG par l’application du test non paramétrique de Wilcoxon retrouve p<0,0001, ce qui signifie la présence d’une différence significative entre les deux groupes. La comparaison des deux groupes Chol par l’application du test paramétrique test T retrouve p<0,0001, ce qui signifie la présence d’une différence significative entre les deux groupes. Conclusion. À travers cette étude, bien qu’elle soit réalisée sur un faible échantillonnage, nous permet de souligner l’importance du jeûne dans l’analyse des paramètres du bilan lipidique, ce qui concorde avec plusieurs travaux de la littérature qui ont permis d’instaurer le jeûne dans les recommandations lors de l’exploration du métabolisme lipidique.

Evaluation of Lipid Profile and Atherogenic Index of Plasma in Patients with Type 2 Diabetes (AIP = log TG/HDL-c)

Aims: The objective of our study was to evaluate the lipid profile and the plasma atherogenicity index obtained from the log (TG / HDL-c) in diabetics patients. Study Design: This is a comparative and analytical study. Place and Duration of Study: Sample: MARC SANKALE Centre at the Abass Ndao Hospital in Dakar (Senegal), CHNU/Fann Biochemistry Laboratory, from June 2018 to November 2019. Controls: For each patient, a witness of the same sex and the same age ± 2 years was recruited. Methodology: The lipid balance parameters were assayed using enzymatic techniques with the Cobas c311 system (Roche Diagnostics, Switzerland). Plasma atherogenicity indices for each patient were calculated (CT / HDL-c, LDL / HDL-c and Log (TG / HDL-c)). Data analysis was performed using XLSTAT software and a p value <0.05 was considered to be a statistically significant difference. Results: Our study concerned 100 subjects with type 2 diabetes. The average age was 50.5 ± 10.80 years old and the sex ratio was 0.58. Evaluation of lipid parameters had shown an increase in diabetic subjects compared to controls for total cholesterol (2.30 g / l) and LDL-cholesterol (1.40 g / l) with significant differences (p < 0.001). We also found that 11% of patients had a CT / HDL-c ratio > 4.5, while 8% had an LDL-c / HDL-c ratio > 3.5 and 26% of patients had a log (Tg / HDL- c) > 0.21. Conclusion: Lipid disturbances constitute significant abnormalities in type 2 diabetic subjects and would predispose them to cardiovascular complications. However, IAP = log (TG / HDL-c) could be considered the most sensitive predictor of cardiovascular risk.

Lipid profile of antiretroviral therapy-naive HIV-infected patients attending infectious diseases service of University Teaching Hospital of Kinshasa, Democratic Republic of the Congo (DRC)

Introduction: HIV infection leads to metabolic disorders. The objective of this work was to study the lipid profile of HIV + patients followed at the University Teaching Hospital of Kinshasa (UTHK). Methods: This study analyzes the lipid profile of HIV + patients, aged at least 18 years, followed at the UTHK from January 1, 2008 to December 31, 2014. The medians of different types of lipids, the frequency of lipid disorders, the general clinical characteristics of patients and factors associated with dyslipidaemia were studied. Haemoglobin (Hb), White Blood Cells (WBC), Leukocyte Formula (LF), Blood Sugar, Urea, Creatinine, Transaminases, Uric Acid, CD4s+ count were analyzed. Results: The lipid balance was performed in 38.8% of patients; 38.1% of them had dyslipidaemia. Total hypercholesterolaemia (28.6%), elevated LDL-C (19%), hypertriglyceridemia (23.8%) and HDL hypocholesterolaemia (42.9%) were observed. The medians of TG (128 mg / dL), HDL-C (51 mg/dL) and LDL-C (78 mg/dL) were high. Risk factors associated with dyslipidaemia were represented by WHO stage 4, tuberculosis (TB) and hyperglycaemia. The highest levels of LDL-C and TG and the lowest HDL-C were seen when CD4s+ were below 200 elements/µL. Conclusion: The HIV/AIDS dyslipidaemia characterized in this study by HDL-C hypocholesterolaemia, hypertriglyceridemia and total and LDL hypercholesterolemia can be considered as an indicator of the progression of HIV infection.

Resveratrol Improves Hepatic Redox Status and Lipid Balance of Neonates with Intrauterine Growth Retardation in a Piglet Model

Abnormal lipid metabolism, oxidative stress (OS), and inflammation play a pivotal role in the increased susceptibility to neonatal fatty liver diseases associated with intrauterine growth retardation (IUGR). This study was firstly conducted to investigate whether resveratrol could alleviate IUGR-induced hepatic lipid accumulation, alteration of redox and immune status in a sucking piglet model and explore the possible mechanisms at transcriptional levels. A total of 36 pairs of 7 d old male normal birth weight (NBW) and IUGR piglets were orally fed with either 80 mg resveratrol/kg body weight/d or 0.5% carboxymethylcellulose sodium for a period of 14 days, respectively. Compared with the NBW piglets, the IUGR piglets displayed compromised growth performance and liver weight, reduced plasma free fatty acid (FFA) level, increased hepatic OS, abnormal hepatic lipid accumulation and weakened hepatic immune function, and hepatic aberrant transcriptional expression of some genes such as heme oxygenase 1, superoxide dismutase 1, sterol regulatory element-binding protein 1c, stearoyl-CoA desaturase 1, liver fatty acid-binding proteins 1, toll-like receptor 4, and tumor necrosis factor alpha (TNF-α). Oral administration of resveratrol to piglets decreased the levels of FFA and total triglycerides (TG) in the plasma and hepatic TNF-α concentration, and increased glutathione reductase activity and reduced glutathione level in the liver. Resveratrol restored the increased alanine aminotransferase activity in the plasma of IUGR piglets. Treatment with resveratrol ameliorated the increased hepatic malondialdehyde, protein carbonyl, TG, and FFA concentrations induced by IUGR. Resveratrol treatment alleviated the reduced lipoprotein lipase activity and its mRNA expression as well as TNF-α gene expression in the liver of IUGR piglets. Hepatic glutathione peroxidase 1 and monocyte chemotactic protein 1 genes expression of piglets was upregulated by oral resveratrol administration. In conclusion, resveratrol administration plays a beneficial role in hepatic redox status and lipid balance of the IUGR piglets.

CITICOLINE APPLICATIONS AS A COMPLEX PRIMARY TREATMENT

This article is about primary open-angle glaucoma (POAG) which is a multifactorial degenerative disease that affects the optic nerve and subsequently leads to the loss of retinal ganglion cells (RGC) and their axons. Therefore, preparations with antioxidant and membrane-stabilizing effect, as well as ensuring restoration of lipid balance, are relevant in the complex therapy of POAG.

Interstitial Leydig Cell Tumorigenesis—Leptin and Adiponectin Signaling in Relation to Aromatase Expression in the Human Testis

Although epidemiological studies from the last years report an increase in the incidences of Leydig cell tumors (previously thought to be a rare disease), the biochemical characteristics of that tumor important for understanding its etiology, diagnosis, and therapy still remains not completely characterized. Our prior studies reported G-protein coupled estrogen receptor signaling and estrogen level disturbances in Leydig cell tumors. In addition, we found that expressions of multi-level-acting lipid balance- and steroidogenesis–controlling proteins including peroxisome proliferator-activated receptor are altered in this tumor. In order to get deeper into the other molecular mechanisms that regulate lipid homeostasis in the Leydig cell tumor, here we investigate the presence and expression of newly-described hormones responsible for lipid homeostasis balancing (leptin and adiponectin), together with expression of estrogen synthase (aromatase). Samples of Leydig cell tumors (n = 20) were obtained from patients (31–45 years old) and used for light and transmission electron microscopic, western blotting, and immunohistochemical analyses. In addition, body mass index (BMI) was calculated. In tumor mass, abundant lipid accumulation in Leydig cells and various alterations of Leydig cell shape, as well as the presence of adipocyte-like cells, were observed. Marked lipid content and various lipid droplet size, especially in obese patients, may indicate alterations in lipid homeostasis, lipid processing, and steroidogenic organelle function in response to interstitial tissue pathological changes. We revealed significantly increased expression of leptin, adiponectin and their receptors, as well as aromatase in Leydig cell tumors in comparison to control. The majority of patients (n = 13) were overweight as indicated by their BMI. Moreover, a significant increase in expression of phospholipase C (PLC), and kinases Raf, ERK which are part of adipokine transductional pathways, was demonstrated. These data expand our previous findings suggesting that in human Leydig cell tumors, estrogen level and signaling, together with lipid status, are related to each other. Increased BMI may contribute to certain biochemical characteristics and function of the Leydig cell in infertile patients with a tumor. In addition, altered adipokine-estrogen microenvironment can have an effect on proliferation, growth, and metastasis of tumor cells. We report here various targets (receptors, enzymes, hormones) controlling lipid balance and estrogen action in Leydig cell tumors indicating their possible usefulness for diagnostics and therapy.

Sex-specific Effects of α2δ-1 in the Ventromedial Hypothalamus of Female Mice Controlling Glucose and Lipid Balance

The thrombospondin receptor alpha2delta-1 (α2δ-1) plays essential roles promoting the activity of SF1 neurons in the ventromedial hypothalamus (VMH) and mediating glucose and lipid metabolism in male mice. Its role in the VMH of female mice remains to be defined, especially considering that this hypothalamic region is sexually dimorphic. We found that α2δ-1 depletion in SF1 neurons differentially affects glucose and lipid balance control and sympathetic tone in females compared to males. Mutant females show a modest increase in relative body weight gain when fed a high-fat diet (HFD) and normal energy expenditure, indicating that α2δ-1 is not a critical regulator of energy balance in females, similar to males. However, diminished α2δ-1 function in the VMH leads to enhanced glycemic control in females fed a chow diet, in contrast to the glucose intolerance reported previously in mutant males. Interestingly, the effects of α2δ-1 on glucose balance in females are influenced by diet. Accordingly, females but not males lacking α2δ-1 exhibit diminished glycemic control as well as susceptibility to hepatic steatosis when fed a HFD. Increased hepatic sympathetic tone and CD36 mRNA expression and reduced adiponectin levels underlie these diet-induced metabolic alterations in mutant females. The results indicate that α2δ-1 in VMH SF1 neurons critically regulates metabolic function through sexually dimorphic mechanisms. These findings are clinically relevant since metabolic alterations have been reported as a side effect in human patients prescribed gabapentinoid drugs, known to inhibit α2δ-1 function, for the treatment of seizure disorders, neuropathic pain, and anxiety disorders.

YejM Modulates Activity of the YciM/FtsH Protease Complex To Prevent Lethal Accumulation of Lipopolysaccharide

ABSTRACT Lipopolysaccharide (LPS) is an essential glycolipid present in the outer membrane (OM) of many Gram-negative bacteria. Balanced biosynthesis of LPS is critical for cell viability; too little LPS weakens the OM, while too much LPS is lethal. In Escherichia coli, this balance is maintained by the YciM/FtsH protease complex, which adjusts LPS levels by degrading the LPS biosynthesis enzyme LpxC. Here, we provide evidence that activity of the YciM/FtsH protease complex is inhibited by the essential protein YejM. Using strains in which LpxC activity is reduced, we show that yciM is epistatic to yejM, demonstrating that YejM acts upstream of YciM to prevent toxic overproduction of LPS. Previous studies have shown that this toxicity can be suppressed by deleting lpp, which codes for a highly abundant OM lipoprotein. It was assumed that deletion of lpp restores lipid balance by increasing the number of acyl chains available for glycerophospholipid biosynthesis. We show that this is not the case. Rather, our data suggest that preventing attachment of lpp to the peptidoglycan sacculus allows excess LPS to be shed in vesicles. We propose that this loss of OM material allows continued transport of LPS to the OM, thus preventing lethal accumulation of LPS within the inner membrane. Overall, our data justify the commitment of three essential inner membrane proteins to avoid toxic over- or underproduction of LPS. IMPORTANCE Gram-negative bacteria are encapsulated by an outer membrane (OM) that is impermeable to large and hydrophobic molecules. As such, these bacteria are intrinsically resistant to several clinically relevant antibiotics. To better understand how the OM is established or maintained, we sought to clarify the function of the essential protein YejM in Escherichia coli. Here, we show that YejM inhibits activity of the YciM/FtsH protease complex, which regulates synthesis of the essential OM glycolipid lipopolysaccharide (LPS). Our data suggest that disrupting proper communication between LPS synthesis and transport to the OM leads to accumulation of LPS within the inner membrane (IM). The lethality associated with this event can be suppressed by increasing OM vesiculation. Our research has identified a completely novel signaling pathway that we propose coordinates LPS synthesis and transport.

Liver X Receptors and Male (In)fertility

Liver X receptors (LXRs) are ligand-dependent transcription factors acting as ‘cholesterol sensors’ to regulate lipid homeostasis in cells. The two isoforms, LXRα (NR1H3) and LXRβ (NR1H2), are differentially expressed, with the former expressed predominantly in metabolically active tissues and the latter more ubiquitously. Both are activated by oxidised cholesterol metabolites, endogenously produced oxysterols. LXRs have important roles in lipid metabolism and inflammation, plus a number of newly emerging roles. They are implicated in regulating lipid balance in normal male reproductive function and may provide a link between male infertility and lipid disorders and/or obesity. Studies from Lxr knockout mouse models provide compelling evidence to support this. More recently published data suggest distinct and overlapping roles of the LXR isoforms in the testis and recent evidence of a role for LXRs in human male fertility. This review summarises the current literature and explores the likely link between LXR, lipid metabolism and male fertility as part of a special issue on Liver X receptors in International Journal of Molecular Sciences.