Several anticancer agents currently used in clinical settings are derived from plants, such as vinblastine vincristine fromCatharanthus roseus, and paclitaxel fromTaxus brevifolia. In this context, the present study investigates the acute and subchronic toxicity ofBerberis hispanica, a medicinal plant traditionally used in North Africa, particularly in the Tikjda region, for its therapeutic properties. The aim was to assess its potential toxic effects on liver and kidney function in Musfemalemusculusmice. The aqueous extract was prepared from the dried root bark through maceration in water, followed by filtration and concentration.cewereMi randomly divided into groups and received daily oral doses of 0, 75, 375, 750, or 1500 mg/kg of extract for six weeks. Acutexiciytowas evaluated based on behavioral changes and mortality within 24 hours. Subchronic toxicity was assessed through biochemicalsesofanaly serum liver enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase) and renal markers (urea,inine,creat albumin), as well as histopathological examination of liver and kidney tissues. No mortality or significant behavioral changeswere observed following acute administration. Subchronic exposure to the highest dose (1500 mg/kg) resulted in a 33 % mortalityand rate mild histological alterations. Biochemical markers showed limited variations compared to controls, suggesting a low levelofpatrenalhe toxicity. These findings indicate that the aqueous extractofBerberis hispanica exhibits low acute and subchronic toxicity in mice, supporting its potential for therapeutic use, pending further pharmacological and toxicological evaluation.

Cardiometabolic disorders, including hepatic steatosis, insulin resistance, and cardiovascular diseases, represent major public health challenges, frequently associated with Western diets high in fats, carbohydrates, and proteins. Dietaryyphenols, pol particularly those found in apples, have shown promising protective effects against metabolic and cardiovascular dysfunctions.This study investigated the therapeutic potential of apple juice in female Wistar rats subjected to a diet-induced model ofmetabolic syndrome. The animals were randomly divided into three groups: a control group (C) fed a standard chow diet; a group fed a high-carbohydrte, high-fat, and high-protein diet (HCHFP; 60 % fat, 30 % carbohydrates, and 9 % protein) for eight weeks; and a third groupP+ (HCHFA) receiving the same diet, supplemented orally with fresh apple juiceMalus (domestica) (15 mL/kg/day) during the final 30 days of the experimental period. Biochemical parameters were assessed in plasma and tissues to evaluate lipid and glucose metabolism,tiveoxida stress (MDA, AOPP, SOD, CAT), inflammatory markers (NO, MCP-1, TNF-alpha), and metabolic regulators (AMPK). Histological examinations of hepatic and cardiac tissues were also performed. Apple juice supplementation significantly improved lipidlycemicandg profiles, enhanced antioxidant enzyme activities, reduced inflammation, and alleviated hepatic steatosis and myocardialThese damage. findings highlight the potential of apple juice as a functional nutritional intervention with antioxidant, anti-inflammatorynd, metabolic regulatory properties against diet-induced cardiometabolic disorders.

Obesity -related pathophysiologies such as insulin resistance and the metabolic syndrome show a markedly increased risk for type 2 diabetes and atherosclerotic cardiovascular disease. This risk appears to be linked to alterations in adipose tissue function, leading to chronic inflammation and the dysregulation of adipocyte-derived factors. Brassica rapa have been used in traditional medicine for the treatment of several diseases, including diabetes.. This study aimed to investigate the effect of nutritional stress induced by a high -fat and high -sucrose diet on the pathophysiology of visceral adipose tissue and the therapeutic effect of Brassica rapa in male Wistar rats. We subjected experimental rats to a high -fat (10 %) high -sucrose (20 %)/per day for 11 months and treated them for 20 days with aqueous extract Br (AEBr) at 200 mg/kg at the end of the experiment. At the time of sacrifice, we monitored plasma and tissue biochemical parameters as well as the morpho-histopathology of visceral adipose tissue. We found AEBr corrected metabolic parameters and inflammatory markers in homogenized visceral adipose tissue and reduced hypertrophy, hyperplasia, and lipid droplets. These results suggest that AEBr enhances anti -diabetic, anti-inflammatory and a protective effect on adipose tissue morphology in type 2 diabetes and obesity.

Endocrine disruptors (ED) are designed by the WHO as “Any chemical substance foreign to the body that can interfere with the functioning of an endocrine system and induce deleterious effects on the latter with a transgenerational effect”. These compounds are present in our environment, carried by air, water, soil and their toxicity is proven because they interact with the hormones synthesis, degradation, transport and mode of action. Exposure of humans and animals to ED through food and/or domestic use is currently a hot topic. The results of numerous independent studies have highlighted the carcinogenic effect of ED, particularly in the case of hormone-dependent cancers. These results provide from experimental and clinical studies. By modifying hormonal function, these compounds have potentially patho-logical consequences for the organism exposed to them or for its descendants. They act by binding to receptors or enzymes and modulate, through their agonist or antagonist activity, the effectiveness or metabolism of natural hormones. The majority of ED are estrogens low-activity. Some are also anti-androgens and/or interfere with the activity of thyroid hormones. ED pose difficult problems, especially since their nature varies over time. Some have been banned, but others persist and concentrate via the food chain in adipose tissue, and cause delayed and multiple effects on human health. Some are toxic for the reproductive function in men via a drop in sperm concentration, others are neurotoxic (Parkinson disease, behavioral disorders) but also those involved in the increasing incidence of chronic diseases, such as type 2 diabetes, obesity and certain hormone-sensitive cancers. Only the cocarcinogenic risk of ED will be discussed in this review, after the presentation of the different families of ED (industrial products in food, food additives, industrial products in packaging, pesticides, substances of natural origin). [Les perturbateurs endocriniens (PE) sont définis par l'OMS comme « toute substance chimique étrangère à l'organisme pouvant interférer avec le fonctionnement d'un système endocrinien et induire des effets délétères sur ce dernier avec un effet transgénérationnel ». Ces composés sont présents dans notre environnement, véhiculés par l’air, l’eau, le sol et leur toxicité est avérée car ils interagissent avec la synthèse, la dégradation, le transport et le mode d’action des hormones. L’exposition des humains et des animaux aux PE par voie alimentaire et/ou domestique est à ce jour un sujet d’actualité. Les résultats de nombreuses études indépendantes ont mis en exergue l’effet cancérigène des PE, notamment dans le cas de cancers hormono-dépendants. Ces résultats proviennent d’études expérimentales et cliniques. Ces composés, en modifiant une fonction hormonale, ont potentiellement des conséquences pathologiques pour l’organisme qui y est exposé ou pour sa descendance. Ils agissent en se liant à des récepteurs ou à des enzymes et modulent, par leur activité agoniste ou antagoniste, l’efficacité ou le métabolisme d’hormones naturelles. La majorité des PE sont des oestrogènes de faible activité. Certains sont également des anti-androgènes et/ou interfèrent avec l’activité des hormones thyroïdiennes. Les PE posent des problèmes difficiles d’autant que leur nature varie dans le temps. Certains ont été interdits, mais d’autres persistent et se concentrent via la chaine alimentaire dans le tissu adipeux et entrainent des effets retardés et multiples sur la santé humaine. Certains sont toxiques pour la fonction de reproduction chez l’homme via une baisse de la concentration de spermatozoïdes, d’autres sont neurotoxiques (maladie de Parkinson, troubles du 32 comportement) mais aussi sont retrouvés ceux impliqués dans l’incidence croissante de maladies chroniques, tels que le diabète de type 2, l’obésité et certains cancers sensibles aux hormones. Ne sera évoqué dans cette revue que le risque cocarcinogène des PE, après la présentation des différentes familles de PE (produits industriels dans les aliments, additifs alimentaires, produits industriels dans les emballages, pesticides, substances d’origine naturelle).]

Endocrine disruptors (ED) are designed by the WHO as “Any chemical substance foreign to the body that can interfere with the functioning of an endocrine system and induce deleterious effects on the latter with a transgenerational effect”. These compounds are present in our environment, carried by air, water, soil and their toxicity is proven because they interact with the hormones synthesis, degradation, transport and mode of action. Exposure of humans and animals to ED through food and/or domestic use is currently a hot topic. The results of numerous independent studies have highlighted the carcinogenic effect of ED, particularly in the case of hormone-dependent cancers. These results provide from experimental and clinical studies. By modifying hormonal function, these compounds have potentially patho-logical consequences for the organism exposed to them or for its descendants. They act by binding to receptors or enzymes and modulate, through their agonist or antagonist activity, the effectiveness or metabolism of natural hormones. The majority of ED are estrogens low-activity. Some are also anti-androgens and/or interfere with the activity of thyroid hormones. ED pose difficult problems, especially since their nature varies over time. Some have been banned, but others persist and concentrate via the food chain in adipose tissue, and cause delayed and multiple effects on human health. Some are toxic for the reproductive function in men via a drop in sperm concentration, others are neurotoxic (Parkinson disease, behavioral disorders) but also those involved in the increasing incidence of chronic diseases, such as type 2 diabetes, obesity and certain hormone-sensitive cancers. Only the cocarcinogenic risk of ED will be discussed in this review, after the presentation of the different families of ED (industrial products in food, food additives, industrial products in packaging, pesticides, substances of natural origin). [Les perturbateurs endocriniens (PE) sont définis par l'OMS comme « toute substance chimique étrangère à l'organisme pouvant interférer avec le fonctionnement d'un système endocrinien et induire des effets délétères sur ce dernier avec un effet transgénérationnel ». Ces composés sont présents dans notre environnement, véhiculés par l’air, l’eau, le sol et leur toxicité est avérée car ils interagissent avec la synthèse, la dégradation, le transport et le mode d’action des hormones. L’exposition des humains et des animaux aux PE par voie alimentaire et/ou domestique est à ce jour un sujet d’actualité. Les résultats de nombreuses études indépendantes ont mis en exergue l’effet cancérigène des PE, notamment dans le cas de cancers hormono-dépendants. Ces résultats proviennent d’études expérimentales et cliniques. Ces composés, en modifiant une fonction hormonale, ont potentiellement des conséquences pathologiques pour l’organisme qui y est exposé ou pour sa descendance. Ils agissent en se liant à des récepteurs ou à des enzymes et modulent, par leur activité agoniste ou antagoniste, l’efficacité ou le métabolisme d’hormones naturelles. La majorité des PE sont des oestrogènes de faible activité. Certains sont également des anti-androgènes et/ou interfèrent avec l’activité des hormones thyroïdiennes. Les PE posent des problèmes difficiles d’autant que leur nature varie dans le temps. Certains ont été interdits, mais d’autres persistent et se concentrent via la chaine alimentaire dans le tissu adipeux et entrainent des effets retardés et multiples sur la santé humaine. Certains sont toxiques pour la fonction de reproduction chez l’homme via une baisse de la concentration de spermatozoïdes, d’autres sont neurotoxiques (maladie de Parkinson, troubles du comportement) mais aussi sont retrouvés ceux impliqués dans l’incidence croissante de maladies chroniques, tels que le diabète de type 2, l’obésité et certains cancers sensibles aux hormones. Ne sera évoqué dans cette revue que le risque cocarcinogène des PE, après la présentation des différentes familles de PE (produits industriels dans les aliments, additifs alimentaires, produits industriels dans les emballages, pesticides, substances d’origine naturelle).]

It has been previously shown that clinical cardiovascular manifestations can be caused by mild changes in thyroid function. However, the implication of angiotensinogen ( Agt ) and vascular smooth muscle cells (VSMCs) dysfunction in the pathophysiology of cardiovascular manifestations in hypothyroidism have not yet been investigated. We induced experimental hypothyroidism in Psammomys obesus by administering carbimazole for five months. At the end of the experiment, the animals were sacrificed and histopathological analysis was performed using Masson's trichrome staining of the aorta and thyroid gland. The expression of the Agt gene and the genes implicated in cholesterol metabolism regulation in the liver and VSMCs was determined by qRT-PCR. Histological observations revealed profound remodeling of the aorta structure in animals with hypothyroidism. In addition, Agt gene expression in the liver was significantly increased. In vitro study, showed that VSMCs from hypothyroid animals overexpressed 3-hydroxy-3-methylglutaryl coenzyme A reductase ( Hmgcr ) and Acyl CoA:cholesterol acyltransferase ( Acat ) 1, with failure to increase the efflux pathway genes (ATP-binding cassette subfamily G member ( Abcg) 1 and 4 ). These results suggest that hypothyroidism leads to vascular alterations, including structural remodeling, VSMCs cholesterol metabolism dysfunction, and their switch to a synthetic phenotype, together with hepatic Agt gene overexpression.

Abstract Thyroid hormones (TH) have several effects on the cardiovascular system. A slight decline in TH levels has harmful effects on the vascular system. The current study aimed to investigate whether a decrease in TH plasma levels was responsible for the expression of some atherosclerosis markers. Experimental hypothyroidism was induced in Psammomys obesus by administering 0.03% carbimazole in their drinking water for five months (M5). The animals were sacrificed at M5, and histopathological analysis of the thoracic aorta and thyroid gland was performed after Masson's trichrome staining. The expression of the angiotensinogen (Agt) gene and the genes implicated in cholesterol metabolism regulation in the liver and vascular smooth muscle cells (VSMCs) was determined by qRT-PCR. Finally, we assessed the in vitro proliferation rate of VSMCs derived from the aortas of the two groups of animals. Hypothyroidism was associated with increased expression of Agt in the liver and 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmgcr) and Acyl CoA:cholesterol acyltransferase (Acat) 1 genes (cholesterol synthesis and esterification pathway) in VSMCs, with failure to increase efflux pathway genes (ATP-binding cassette subfamily G member (Abcg) 1 and 4) in these vascular cells. Moreover, reduction in TH induces aortic endothelial cell and subendothelium hypertrophy, and disorganization of the media with rupture of the elastic fiber network. All these results suggest that hypothyroidism can lead to atherosclerosis through the alteration of the physiology of VSMCs, mainly the phenotype switch and gene expression modification involved in the regulation of cholesterol metabolism.

Plusieurs études ont montré que les taux plasmatiques en homocystéine (Hcy) supérieurs à 14 μMol/L, indépendamment des facteurs de risques dits traditionnels, sont impliqués dans des désordres et dysfonctionnements du système vasculaire. C’est pourquoi développer une démarche thérapeutique visant à normaliser ou réduire l’Hcy est un enjeu de santé publique. Le but de ce travail est d’analyser l’impact d’une surcharge en méthionine sur certaines enzymes du cycle de la méthionine et du stress oxydatif et sa répercussion sur le remodelage du tissu cardiaque. Des rats Wistar mâles sont divisés en 05 groupes, lot 1(NaCl), Lot 2 (Huile d’olive), lot 3 (05 mg de lycopène/Kg de PC, lot 4 (500 mg de méthionine/Kg de P.C/J), et le lot 5 (05 mg de lycopène et 500 mg de méthionine/Kg de P.C/J). La méthionine et le lycopène sont administrés par voie orale tous les jours pendant trois mois. La pesée corporelle, le dosage de l’Hcy, de certains enzymes (CBS, SAHH, PON1, MDA et la MPO) sont réalisés. Au terme de l’expérimentation, nous avons procédé à une analyse histologique du tissu cardiaque avec une attention particulière à la matrice extracellulaire (MEC). L’administration chronique de la méthionine a révélé une augmentation significative de l’Hcy, du MDA et de la MPO et une diminution de la SAHH de la CBS et de la PON1. Le traitement préventif par le lycopène a restauré significativement l’équilibre biochimique des activités des enzymes étudiés. Au niveau tissulaire, nous avons noté la présence de diverses altérations touchant aussi bien les cellules que la matrice extracellulaire cardiaque. Cette étude suggère que les altérations biochimiques et tissulaires engendrées par l’installation d’un état d’hyperhomocystéinémie, sont réduites par la supplémentation en lycopène, lequel exerce son effet protecteur grâce à ses propriétés anti-oxydantes, anti-agrégantes plaquettaires, et modulateur du stress oxydatif.

Objectives. - The tissue renin-angiotensin system (tRAS) plays a key role in the maintenance of cellular homeostasis but is also implicated in atherosclerosis. Thyroid hormone (TH) contributes, via genomic effects, to control of tRAS gene expression in the arterial wall and vascular smooth muscle cells (VSMCs). We investigated the specific functions of TH receptors-alpha and -beta (TR alpha and TR beta) on tRAS gene expression in the aorta and VSMCs, and the potential protective effect of TR alpha against atherosclerosis. Material and methods. - Using aorta and cultured aortic VSMCs from TR alpha and TR beta deficient mice, tRAS gene expression was analyzed by determining mRNA levels on real-time PCR. Gene regulation under cholesterol loading mimicking atherosclerosis conditions was also examined in VSMCs in vitro. Results. - TR alpha deletion significantly increased expression of angiotensinogen (AGT) and angiotensin II receptor type 1 subtype a (AT(1)R(a)) at transcriptional level in aorta, a tissue with high TR alpha expression level. TR alpha activity thus seems to be required for maintenance of physiological levels of AGTand AT(1)R(a) expression in the arterial wall. In addition, during cholesterol loading, TR alpha deletion significantly increased cholesterol content in VSMCs, with a weaker decrease in AGTexpression. Conclusion. - TR alpha seems to have an inhibitory impact on AGTand AT I R a expression, and loss of TR alpha function in TR alpha 0/0 mice increases tRAS expression in the aortic wall. More importantly, TR alpha deletion significantly increases VSMC cholesterol content. Our results are consistent with a protective role of TR alpha against atherosclerosis. (C) 2018 Elsevier Masson SAS. All rights reserved.

Thyroid hormone (TH) regulates gene transcription by binding to TH receptors (TRs). TRs regulate the genes of lipid metabolism and the renin-angiotensin system (RAS). We examined the effect of TRα deletion in ApoE–/– mice (DKO mice) on the following: (i) the expression of genes controlling cholesterol metabolism and tissue (t)RAS in the liver and aorta and (ii) the expression of these genes and the regulation of cholesterol content in cultured vascular smooth muscle cells (VSMCs). TRα deletion in ApoE–/– mice led to the repression of genes involved in the synthesis and influx of cholesterol in the liver. However, TRα deletion in the arterial wall suppressed the expression of genes involved in the esterification and excretion of cholesterol and enhanced the expression of angiotensinogen (AGT). The VSMCs of the ApoE–/– and DKO mice increased their cholesterol content during cholesterol loading, but failed to increase the expression of ATP-binding cassette transporter A1 (ABCA1). T3 addition partially corrected these abnormalities in the cells of the ApoE–/– mice but not those of the DKO mice. In conclusion, TRα deletion in ApoE–/– mice slightly increases the expression of tRAS in the aorta and aggravates the dysregulation of cholesterol content in the VSMCs.

In atherosclerosis studies, there are few data, especially in men, on the biology of perivascular adipose tissue (PVAT) compared to that of other adipose tissue (AT), on amendments in obesity, and its possible role in the development of atherosclerosis. We conducted an ex vivo human study on pericarotid adipose tissue-collected in the immediate vicinity (PVATp) and away from the plate (tapas)-and subcutaneous (SC) neck gathered during surgery from patients suffering from atheromatous carotid disease. In addition, we conducted a study in obese Zucker rats (models of obesity and insulin resistance) and Wistar rats subjected to moderate stress. In these models, we collected renal adipose tissue (RAT), epididymal adipose tissue (EAT), and TAPA samples. On all samples, we measured mRNA levels encoding for proinflammatory cytokines (TNFa, IL-6, IL-1b, MCP-1). Our results showed an increase in mRNA MCP-1, TNF and IL-6 in the adipose tissue around atherosclerotic plaques, an increase that was greater in diabetics than in non-diabetic subjects; we noted for the mRNA of MCP-1 in the TAPAp, 3.49 x 10 (2) +/- 1.17 x 10 (2) ng/ug 18S in diabetic patients compared to 7.26 x 10 (3) +/- 1.00 x 10 (3) ng/ug 18S (** P < 0.01) in non-diabetic patients. In the obese Zucker rat, we found a significant increase in IL-6 in TAPA in obese animals compared to the corresponding controls (4.24 x 10 (5) +/- 1.75 x 10 (6) ng/mg 18S vs 1.29 x 10 (5) +/- 1.55 x 10 (6) ng/ug 18S). In stressed rats, we recorded a TNFa mRNA increase in the PVAT and EAT in the stressed rats compared to fatty tissue of control animals, we note respectively, 7.52 x 10 (3) +/- 2.8 x 10 (3) ng/mg 18S vs 2.62 x 10 (3) +/- 0.57 x 10 (3) ng/18S and 4.78 x 10 (3) +/- 1.52 x 10 (3) ng/mg 18S vs 2.02 x 10 (3) +/- 0.3 x 10 (3) ng/ug 18S. In summary, our work shows an inflammatory state of the TAPA surrounding the atheromatous plaques in diabetic patients. An obesity or stress state promotes an inflammatory profile of PVAT. (C) 2017 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.

In atherosclerosis studies, there are few data, especially in men, on the biology of perivascular adipose tissue (PVAT) compared to that of other adipose tissue (AT), on amendments in obesity, and its possible role in the development of atherosclerosis. We conducted an ex vivo human study on pericarotid adipose tissue-collected in the immediate vicinity (PVATp) and away from the plate (tapas)-and subcutaneous (SC) neck gathered during surgery from patients suffering from atheromatous carotid disease. In addition, we conducted a study in obese Zucker rats (models of obesity and insulin resistance) and Wistar rats subjected to moderate stress. In these models, we collected renal adipose tissue (RAT), epididymal adipose tissue (EAT), and TAPA samples. On all samples, we measured mRNA levels encoding for proinflammatory cytokines (TNFα, IL-6, IL-1β, MCP-1). Our results showed an increase in mRNA MCP-1, TNF and IL-6 in the adipose tissue around atherosclerotic plaques, an increase that was greater in diabetics than in non-diabetic subjects; we noted for the mRNA of MCP-1 in the TAPAp, 3.49×10-2±1.17×10-2ng/ug 18S in diabetic patients compared to 7.26×10-3±1.00×10-3ng/ug 18S (**P<0.01) in non-diabetic patients. In the obese Zucker rat, we found a significant increase in IL-6 in TAPA in obese animals compared to the corresponding controls (4.24×10-5±1.75×10-6ng/μg 18S vs 1.29×10-5±1.55×10-6ng/ug 18S). In stressed rats, we recorded a TNFα mRNA increase in the PVAT and EAT in the stressed rats compared to fatty tissue of control animals, we note respectively, 7.52×10-3±2.8×10-3ng/μg 18S vs 2.62×10-3±0.57×10-3ng/18S and 4.78×10-3±1.52×10-3ng/μg 18S vs 2.02×10-3±0.3×10-3ng/ug 18S. In summary, our work shows an inflammatory state of the TAPA surrounding the atheromatous plaques in diabetic patients. An obesity or stress state promotes an inflammatory profile of PVAT.

Objective: Chronic hyperglycemia characteristic of type diabetes 2 is responsible for the accelerated atherosclerosis with increased cardiovascular risk. In this study, we will propose to analyze the effect of a long-term of glucotoxicity in vivo in Psammomys obesus by addition of sucrose to 30% for 11 months and in vitro study of adventitial fibroblasts in the presence of D-glucose 0.6% for 7 days. Materials and methods: Evaluation of plasma biochemical parameters was carried out at the initial time and at the end of experiment. At autopsy, a morphological study of the aorta was performed after fixation in aqueous Bouin and staining with Masson’s trichrome. The experimental glucotoxicity is induced by incubation of fibroblasts in DMEM enriched with D-glucose at 0.6% for 7 days. The impact of glucotoxicity is assessed in the intracellular compartments through dosage of total nitrite and malondialdehyde, a product of lipid peroxidation, and thanks to a morphological assay after fixation of cells with aqueous bouin and blood staining with May Grünwald Giemsa. The evaluation of cell proliferation is accomplished by cell counting. Collagens I and III of the extracellular compartment are characterized by SDS-PAGE. Results: Animals subjected to sucrose showed hyperglycemia associated with hyperinsulinemia, dyslipidemia, hyperproteinemia, increased CPK and VLDL-LDL and decreased HDL. Histology of aortas revealed endothelial cells hypertrophy, severe disorganization of intima and media. In the presence of glucose, the proliferation of fibroblasts increases very significantly (P = 2.34 × 10-5), the rate of malonaldehyde, nitrite and total density of chains α2 (I) and α1 (I + III) extra-cellular collagens I and III increased significantly. After staining, the cells showed hypertrophy, vacuolation of cytoplasm and chromatin condensation with nuclear fragmentation, indicative of apoptosis. Conclusion: The glucotoxicity induced in vivo and in vitro is responsible for major structural and metabolic alterations leading to the acceleration of the atherosclerotic process.

Perilipin 1 is involved in the control of adipose tissue triacylglycerol hydrolysis. Its ablation in mice decreases fat mass and induces a partial resistance to diet-induced and genetic obesity. However, the consequences of perilipin 1 invalidation on energy balance are not fully defined. Moreover, the impact of perilipin 1 ablation on exercise performance and on fatty acids mobilization and utilization during exercise has not been studied. We compared energy balance (food intake, energy expenditure, spontaneous physical activity) and response to exercise of Plin1(-/-) and wild-type mice receiving a chow diet. The Plin1(-/-) mice had less fat, comparable food intake, comparable or slightly decreased energy expenditure, and no change in spontaneous physical activity. Mean 24-hour respiratory quotient was slightly lower, suggesting enhanced fatty acid oxidation. Exercise performance (both acute and endurance) was not impaired. Changes in nonesterified fatty acid levels during exercise were comparable, showing that triacylglycerol mobilization was unimpaired. Oxygen consumption increased faster (both tests) and to higher values (acute exercise) in Plin1(-/-) mice. Respiratory quotient increased during both types of exercise in Plin1(-/-) and control mice, but less in Plin1(-/-) mice. These lower respiratory quotient values show that Plin1(-/-) mice rely more on fatty acid oxidation during exercise. This is probably related to an overexpression in liver and muscle of genes for fatty acids oxidation. Perilipin 1 ablation has limited consequences on energy balance. It does not impair exercise performance; fatty acids mobilization during exercise is not impaired, whereas their oxidation is enhanced.

Nous avons etudie l’expression et la regulation de la lipogenese dans les aortes et CMLV et determine si elle est modifiee par l’insulino-resistance et le diabete. Les rats Zucker obeses (ZO), diabetiques et Psammomys obesus accumulent plus de lipides dans leurs aortes que leurs controles. Cependant l’expression des genes de la lipogenese et ceux impliques dans la captation des acides gras, n’est pas augmentee. Un resultat similaire a ete retrouve dans des pieces d’endarteriectomies chez l’homme. Le milieu adipogenique, le glucose ou l’insuline seule stimulent moderement la lipogenese uniquement dans les CML de Zucker controles, aucun effet n’a ete observe dans les CML de ZO. Nous avons montre que les effets du TO901317 sur la lipogenese dans les CMLV sont dus uniquement a l’activation du recepteur nucleaire LXRα, PXR n’a aucun effet. En conclusion, la lipogenese n’est pas augmentee dans la paroi arterielle durant l’insulino-resistance et le diabete.

Aim. - Lipogenesis is expressed in vascular smooth muscle cells (VSMCs), and such in situ lipogenesis could be providing the fatty acids for triglyceride synthesis and cholesterol esterification, and contributing to lipid accumulation in the arterial wall. This study investigated both the expression and regulation of lipogenesis in VSMCs to determine if they are modified in Psammomys obesus gerbils fed a high-fat diet as a model of insulin resistance and diabetes.Methods. - Aortas were collected from diabetic and non-diabetic P. obesus for histological examination, measurement of lipogenic gene expression and VSMC culture.Results. - The aortas of diabetic animals exhibited lipid deposits and foam cells as well as disorganization of elastic fibres. However, lipogenic gene expression was not modified. VSMCs in vitro from the aortas of diabetic animals had, compared with cells from non-diabetic animals, lower mRNA levels of SREBP-1c and ChREBP. An adipogenic medium stimulated moderate FAS and ACC1 expression in cells from both diabetic and non-diabetic animals, but glucose and insulin on their own had no such stimulatory action. Also, triiodothyronine (T3) had a clear stimulatory action, while angiotensin It had a moderate effect, in cells from non-diabetic P. obesus, but not from diabetic animals, whereas LXR agonists stimulated lipogenesis in cells from both animal groups.Conclusion. - Lipogenesis is expressed in the arterial walls and VSMCs of P. obesus. However, its expression was not increased in diabetes, and did not respond to either T3 or angiotensin II. Therefore, lipogenesis in situ is unlikely to contribute to the accumulation of lipids in the arterial walls of diabetic P. obesus gerbils. (C) 2010 Elsevier Masson SAS. All rights reserved.

Background: Vascular smooth muscular cells (VSMC) express lipogenic genes. Therefore in situ lipogenesis could provide fatty acids for triglycerides synthesis and cholesterol esterification and contribute to lipid accumulation in arterial wall with aging and during atheroma.Methods: We investigated expression of lipogenic genes in human and rat arterial walls, its regulation in cultured VSMC and determined if it is modified during insulin-resistance and diabetes, situations with increased risk for atheroma.Results: Zucker obese (ZO) and diabetic (ZDF) rats accumulated more triglycerides in their aortas than their respective control rats, and this triglycerides content increased with age in ZDF and control rats. However the expression in aortas of lipogenic genes, or of genes involved in fatty acids uptake, was not higher in ZDF and ZO rats and did not increase with age. Expression of lipogenesis-related genes was not increased in human arterial wall (carotid endarterectomy) of diabetic compared to non-diabetic patients. In vitro, glucose and adipogenic medium (ADM) stimulated moderately the expression and activity of lipogenesis in VSMC from control rats. LXR agonists, but not PXR agonist, stimulated also lipogenesis in VSMC but not in arterial wall in vivo. Lipogenic genes expression was lower in VSMC from ZO rats and not stimulated by glucose or ADM.Conclusion: Lipogenic genes are expressed in arterial wall and VSMC; this expression is stimulated (VSMC) by glucose, ADM and LXR agonists. During insulin-resistance and diabetes, this expression is not increased and resists to the actions of glucose and ADM. It is unlikely that this metabolic pathway contribute to lipid accumulation of arterial wall during insulin-resistance and diabetes and thus to the increased risk of atheroma observed in these situations.