Plasma and Aorta Biochemistry and MMPs Activities in Female Rabbit Fed Methionine Enriched Diet and Their Offspring

This study investigated whether a high Met diet influences biochemical parameters, MMPs activities in plasma, and biochemical and histological remodeling in aorta, in both pregnant female rabbits and their offspring. Four female rabbit groups are constituted (each n=8), nonpregnant control (NPC), pregnant control (PC) that received normal commercial chow, nonpregnant Met (NPMet), and pregnant Met (PMet) that received the same diet supplemented with 0,35% L-methionine (w/w) for 3 months (500 mg/d). All pregnant females realize 3 successive pregnancies. Plasma results showed that Met excess increased Hcy, raised CRP in NPMet and decreased it in PMet, enhanced significantly proMMP-2 and proMMP-9 activities in NPMet, and reduced them in PMet. Aorta showed a rise in collagen level, essentially in PMet, a reduction of elastin content in both PMet and NPMet, and a significant decrease in lipid content in PMet, with histological changes that are more pronounced in NPMet than PMet. Met excess enhanced proMMP-9 activities in NPMet while it decreased them in PMet. PMet newborn presented increase in uremia and CRP and significant rise of active MMP-2 and MMP-9 forms. In aorta, media and adventitia thickness increased, total lipids content decreased, proMMP-9 activity decreased, and proMMP-2 activity increased

Lipogenesis in arterial wall and vascular smooth muscular cells: regulation and abnormalities in insulin-resistance

<p>Abstract</p> <p>Background</p> <p>Vascular smooth muscular cells (VSMC) express lipogenic genes. Therefore <it>in situ </it>lipogenesis could provide fatty acids for triglycerides synthesis and cholesterol esterification and contribute to lipid accumulation in arterial wall with aging and during atheroma.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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. <it>In vitro</it>, 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 <it>in vivo</it>. Lipogenic genes expression was lower in VSMC from ZO rats and not stimulated by glucose or ADM.</p> <p>Conclusion</p> <p>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.</p

The role of homocysteine in seminal vesicles remodeling in rat

Introduction. Elevated plasma homocysteine (Hcy) levels have been associated with several tissue injuries including heart and liver fibrosis. In these diseases, hyperhomocysteinemia (Hhcy) plays a major role in modulating the alteration of the balance between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMPs), leading to the pathological accumulation of extracellular matrix (ECM) proteins. Since the effect of Hhcy on ECM of seminal vesicle was not studied, the aim of our research was to check if Hcy can induce a remodeling within seminal vesicles ECM. Material and methods. The study was conducted in 22 adult male Wistar rats. The rats were divided into two groups: a control group, which received standard diet and tap water; the treated group received the same diet and water supplemented with solution of L-methionine (200 mg/kg b.w./day) for 6 months. Plasma homocysteine concentration was measured. Histological changes were observed with light microscope. The presence of collagen I and III and metalloproteinases (2, 3, 7 and 9) in the seminal vesicles was examined using immunohistochemistry and Western blotting. Results. Plasma Hcy levels increased significantly after methionine treatment and interfered significantly with body weight in treated rats. The content of fibrillar collagens (I and III) in the wall of seminal vesicles was elevated in hyperhomocysteinemic rats. Moreover, we found that hyperhomocysteinemia increased the expression of MMP-2, -3, -7 and -9 in seminal vesicles of experimental rats. Conclusions. Increased plasma concentration of Hcy accompanied by the accumulation of collagen and upregulation of MMPs in rat seminal vesicles might contribute to the remodeling of seminal vesicles.

The role of homocysteine in seminal vesicles remodeling in rat

Elevated plasma homocysteine (Hcy) levels have been associated with several tissue injuries including heart and liver fibrosis. In these diseases, hyperhomocysteinemia (Hhcy) plays a major role in modulating the alteration of the balance between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMPs), leading to the pathological accumulation of extracellular matrix (ECM) proteins. Since the effect of Hhcy on ECM of seminal vesicle was not studied, the aim of our research was to check if Hcy can induce a remodeling within seminal vesicles ECM. Material and methods. The study was conducted in 22 adult male Wistar rats. The rats were divided into two groups: a control group, which received standard diet and tap water; the treated group received the same diet and water supplemented with solution of L-methionine (200 mg/kg b.w./day) for 6 months. Plasma homocysteine concentration was measured. Histological changes were observed with light microscope. The presence of collagen I and III and metalloproteinases (2, 3, 7 and 9) in the seminal vesicles was examined using immunohistochemistry and Western blotting. Results. Plasma Hcy levels increased significantly after methionine treatment and interfered significantly with body weight in treated rats. The content of fibrillar collagens (I and III) in the wall of seminal vesicles was elevated in hyperhomocysteinemic rats. Moreover, we found that hyperhomocysteinemia increased the expression of MMP-2, -3, -7 and -9 in seminal vesicles of experimental rats. Conclusions. Increased plasma concentration of Hcy accompanied by the accumulation of collagen and upregulation of MMPs in rat seminal vesicles might contribute to the remodeling of seminal vesicles. Folia Histochemica et Cytobiologica 2017, Vol. 55, No. 2, 62–73

Time-Restricted Feeding Improves Body Weight Gain, Lipid Profiles, and Atherogenic Indices in Cafeteria-Diet-Fed Rats: Role of Browning of Inguinal White Adipose Tissue

We would like to express our appreciation to all staff from Diabesity-UGR group (AnaTorrices, DiegoSalagre, and Juan Miguel Leiva) for their technical support and for being attentive to answer our research questions and to AsmaAmalou from Physiopathology-USTHB group for the animal sacrifice assistance. We would also like to express our warmest thanks to NemchaLebaili and her staff from ÉcoleNormaleSupérieure (Kouba, Algiers) for the use of their animal facilities.The following are available online at http://www.mdpi.com/2072-6643/12/8/2185/s1, Table S1: normal chow and cafeteria food items compositions as given by the product manufacturers.Time-restricted feeding (TRF) showed a potent effect in preventing obesity and improving metabolicoutcomes in several animal models of obesity. However, there is, as of yet, scarce evidence concerning its effectiveness against obesogenic challenges that more accurately mimic human Western diets, such as the cafeteria diet. Moreover, the mechanism for its efficacy is poorly understood. White adipose browning has been linked to body weight loss. Herein, we tested whether TRF has the potential to induce browning of inguinal white adipose tissue (iWAT) and to attenuate obesity and associated dyslipidemia in a cafeteria-diet-induced obesity model. Male Wistar rats were fed normal laboratory chow (NC) or cafeteria diet (CAF) for 16 weeks and were subdivided into two groups that were subjected to either ad libitum (ad lib, A) or TRF (R) for 8 h per day. Rats under the TRF regimen had a lower body weight gain and adiposity than the diet-matchedad lib rats, despite equivalent levels of food intake and locomotor activity. In addition, TRF improved the deranged lipid profile (total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-c), low-density lipoprotein (LDL-c)) and atherogenic indices (atherogenic index of plasma (AIP), atherogenic coefficient (AC), coronary risk index (CRI) in CAF-fed rats. Remarkably, TRF resulted in decreased size of adipocytes and induced emergence of multilocular brown-like adipocytes in iWAT of NC- and CAF-fed rats. Protein expression of browning markers, such as uncoupling protein-1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), were also up-regulated in the iWAToftime-restricted NC- or CAF-fed rats. These findings suggest that a TRF regimen is an effective strategy to improve CAF diet-induced obesity, probably via a mechanismthe involving WAT browning process.Ministerio de Economia y Competitividad (Spain) SAF2016-79794-RErasmus + Mobility Program Dimension Internacional from "European Commission" KA 10

In Vivo Subacute Toxicity and Antidiabetic Effect of Aqueous Extract of Nigella sativa

Context. Nigella sativa seeds are usually used as traditional medicine for a wide range of therapeutic purposes. Objective. To investigate the subacute toxicity of NS aqueous extract and select its lowest dose to study its antidiabetic effect. Methods. 5 AqE.NS doses (2, 6.4, 21, 33, and 60 g/Kg) were daily administered to mice by gavage. Biochemical parameters measurements and histological study of the liver and the kidney were performed after 6 weeks of supplementation. Thereafter, and after inducing diabetes by alloxan, rats were treated by 2 g/Kg of AqE.NS during 8 weeks. Metabolic parameters were measured on sera. A horizontal electrophoresis of plasmatic lipoprotein was conducted. Glycogen, total lipids, and triglycerides were measured in the liver. TBARS were evaluated on adipose tissue, liver, and pancreas. Results. AqE.NS showed no variation in urea and albumin at the 5 doses, but hepatotoxicity from 21 g/Kg was confirmed by histopathological observations of the liver. In diabetic rats, AqE.NS significantly decreased glycemia, TG, T-cholesterol, LDL-c, and TBARS and showed a restored insulinemia and a significant increase in HDL-c. Results on the liver indicated a decrease in lipids and a possible glycogenogenesis. Conclusion. AqE.NS showed its safety at low doses and its evident antihyperglycemic, antihyperlipidemic, and antioxidant effect

Myocardial structural and biological anomalies induced by high fat diet in Psammomys obesus gerbils

Background: Psammomys obesus gerbils are particularly prone to develop diabetes and obesity after brief period of abundant food intake. A hypercaloric high fat diet has been shown to affect cardiac function. Here, we sought to determine whether a short period of high fat feeding might alter myocardial structure and expression of calcium handling proteins in this particular strain of gerbils. Methods: Twenty Psammomys obesus gerbils were randomly assigned to receive a normal plant diet (controls) or a high fat diet. At baseline and 16-week later, body weight, plasma biochemical parameters (including lipid and carbohydrate levels) were evaluated. Myocardial samples were collected for pathobiological evaluation. Results: Sixteen-week high fat dieting resulted in body weight gain and hyperlipidemia, while levels of carbohydrates remained unchanged. At myocardial level, high fat diet induced structural disorganization, including cardiomyocyte hypertrophy, lipid accumulation, interstitial and perivascular fibrosis and increased number of infiltrating neutrophils. Myocardial expressions of pro-apoptotic Bax-to-Bcl-2 ratio, pro-inflammatory cytokines [interleukin (IL)-1β and tumor necrosis factor (TNF)-α], intercellular (ICAM1) and vascular adhesion molecules (VCAM1) increased, while gene encoding cardiac muscle protein, the alpha myosin heavy polypeptide (MYH6), was downregulated. Myocardial expressions of sarco(endo)plasmic calcium-ATPase (SERCA2) and voltage-dependent calcium channel (Cacna1c) decreased, while protein kinase A (PKA) and calcium-calmodulin-dependent protein kinase (CaMK2D) expressions increased. Myocardial expressions of ryanodine receptor, phospholamban and sodium/calcium exchanger (Slc8a1) did not change. Conclusions: We conclude that a relative short period of high fat diet in Psammomys obesus results in severe alterations of cardiac structure, activation of inflammatory and apoptotic processes, and altered expression of calcium-cycling determinants.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

High fat diet altered cardiac metabolic gene profile in Psammomys obesus gerbils.

In metabolic disorders, myocardial fatty infiltration is critically associated with lipotoxic cardiomyopathy.info:eu-repo/semantics/publishe

Thyroid Hormone Receptor Alpha Deletion in ApoE^–/– Mice Alters the Arterial Renin-Angiotensin System and Vascular Smooth Muscular Cell Cholesterol Metabolism

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