Chronic consumption of imbalance diets high in sucrose or fat induces abdominal obesity with different pattern of metabolic disturbances and lost in Langerhans cells population.

Aim: Obesity is a worldwide health issue, associated with development of type 2 Diabetes Mellitus. The aim of this study is to analyze the effect of consumption of two hypercaloric diets on metabolic disturbance and beta cells damage.

Main Methods: Male Wistar rats were subjected to twelve months consumption of three diets: a Control balanced diet (CTD, carbohydrates 58 %, proteins 29 %, lipids 13 %) and two hypercaloric diets, high in sucrose (HSD, carbohydrates 68 %, proteins 22 %, lipids 10 %) or high in fat (HFD, carbohydrates 31 %, proteins 14 %, lipids 55 %).

Differential disruption on glucose and insulin metabolism in two rat models of diet-induced obesity, based on carbohydrates or lipids.

Obesity is a relevant health public issue and is the main factor for glucose metabolism dysregulation and diabetes progression; however, the differential role of a high-fat diet or high sugar diet consumption on glucose metabolism and insulin processing is not well understood and has been scarcely described. Our research aimed to analyze the effects of chronic consumption of both high sucrose and high-fat diets on glucose and insulin metabolism regulation. Wistar rats were fed with high-sugar or high-fat diets for 12 months; after that, fasting glucose and insulin levels were measured along with a glucose tolerance test (GTT).

Chronic exposure to ozone induces cardiac antioxidant response and overexpression of either mitochondrial fision protein DRP1 and hipertrophyc-related proteins.

Pollution is considered a risk factor for cardiovascular disease; however, the mechanisms to explain this relationship are not well understood; ozone is one of the most abundant and studied air contaminants. Our study aimed to evaluate the effect of chronic exposition of rats to controlled low doses of ozone on oxidative stress, apoptosis, mitochondrial dynamics, and cardiac hypertrophy. Male Wistar rats were daily exposed to low ozone doses during 7, 15, 30, and 60 days, 4 h/day.

Anthropometric, biochemical, and haematological indicators associated with hyperhomocysteinemia and their relation to global DNA methylation in a young adult population.

Increased homocysteine (Hcy) levels have been associated with a higher risk of cardiovascular and neurodegenerative diseases. Passive DNA demethylation has been suggested as one of the mechanisms implicated in the development of these conditions, and most studies have investigated this relationship in older adult populations. Therefore, this study aimed to evaluate the relationship between corporal composition and biochemical and haematological indicators with plasma homocysteine levels and genome-wide methylation (Alu, LINE-1, and SAT2) in a population of healthy young adults (median age, 18 years).

The high-risk HPV E6 proteins modify the activity of the eIF4E protein via the MEK/ERK and AKT/PKB pathways.

Previous studies have proposed that the human papillomavirus (HPV) E6 oncoproteins modify the transcriptional activity of eIF4E through mechanisms dependent on p53 degradation. However, the effect of these oncoproteins on pathways regulating the activity of the eIF4E protein remains poorly understood. Hence, we investigated the mechanisms whereby E6 proteins regulate the activity of the eIF4E protein and its effect on target genes.

High sugar but not high fat diet consumption induces hepatic metabolic disruption and up-regulation of mitochondrial fission-associated protein Drp1 in a model of moderate obesity.

Identification of new modifications and the association with diet patterns are essential for the prevention of non-alcoholic fatty liver disease (NAFLD). To address this problem, we feed rats with high caloric diets based on high sucrose (HSD) and high fat (HFD) and analysed metabolic and mitochondrial alterations. Both diets induce moderated obesity and fat accumulation in the liver after 8, 10 and 12 months of diet.

Molecular epidemiology of bacterial vaginosis and its association with genital micro-organisms in asymptomatic women.

. Bacterial vaginosis (BV) is dysbiosis associated with an increased risk of several sexually transmitted infections. It is primarily diagnosed via Gram staining, although molecular analyses have presented higher diagnostic accuracy.

Leptin Modifies the Rat Heart Performance Associated with Mitochondrial Dysfunction Independently of Its Prohypertrophic Effects.

Background: Functional receptors for leptin were described on the surface of cardiomyocytes, and there was a prohypertrophic effect with high concentrations of the cytokine. Therefore, leptin could be a link between obesity and the prevalence of cardiovascular diseases. On the other hand, a deleterious effect of leptin on mitochondrial performance was described, which was also associated with the evolution of cardiac hypertrophy to heart failure.

In female rat heart mitochondria, oophorectomy results in loss of oxidative phosphorylation.

Oophorectomy in adult rats affected cardiac mitochondrial function. Progression of mitochondrial alterations was assessed at one, two and three months after surgery: at one month, very slight changes were observed, which increased at two and three months. Gradual effects included decrease in the rates of oxygen consumption and in respiratory uncoupling in the presence of complex I substrates, as well as compromised Ca buffering ability.

Identification of functional leptin receptors expressed in ventricular mitochondria.

Leptin is a 16 kDa pro-satiety peptide produced primarily not only by white adipocytes but also by numerous other tissues including the heart. Circulating leptin exerts its effect through specific receptors, although its principle actions are dependent on the activation of the long form of the leptin receptor, termed OBRb. As leptin is also produced within the cardiomyocyte, we hypothesized that the peptide can also exert effects by targeting intracellular sites.

Lactation reduces stress-caused dopaminergic activity and enhances GABAergic activity in the rat medial prefrontal cortex.

We investigated the effect of restraint on the release of dopamine, GABA and glutamate in the medial prefrontal cortex (mPFC) of lactating compared with virgin Wistar female rats; besides the expression of D1, neuropeptide Y Y2, GABA receptors and corticotropin-releasing factor (CRF). Results from microdialysis experiments showed that basal dopamine and GABA, but not glutamate, concentrations were higher in lactating rats. In virgin animals, immobilization caused significant increase in dopamine, whereas GABA was unchanged and glutamate reduced.

Bax induces cytochrome c release by multiple mechanisms in mitochondria from MCF7 cells.

Bax, a pro-apoptotic member of the Bcl-2 family of proteins has the ability to form transmembrane pores large enough to allow cytochrome c (Cyt c) release, as well as to activate the mitochondrial permeability transition pore (mPTP); however, no differential study has been conducted to clarify which one of these mechanisms predominates over the other in the same system. In the present study, we treated isolated mitochondria from MCF7 cells with recombinant protein Bax and tested the efficacy of the mPTP inhibitor cyclosporin A (CsA) and of the Bax channel blocker (Bcb) to inhibit cytochrome c release. We also, induced apoptosis in MCF7 cell cultures with TNF-α plus cycloheximide to determine the effect of such compounds in apoptosis induction via mPTP or Bax oligomerization.

Postconditioning protects against reperfusion injury in hypertensive dilated cardiomyopathy by activating MEK/ERK1/2 signaling.

Background: Postconditioning (PostC) cardioprotection has been related to up-regulation of survival kinases; however, the efficacy of PostC and the role of ERK1/2 (extracellular signal-regulated kinase 1/2) remain to be substantiated in hypertension states that may produce "pathologic remodeling." Therefore, in this work we compared PostC effect and assessed the role of ERK1/2 activation in a model of hypertensive dilated cardiomyopathy (DCM), versus normal (Sham) and compensated hypertrophy (CH) models.

Methods And Results: Rats were subjected to angiotensin II administration until development of cardiovascular diseases.

Leptin-induced cardiomyocyte hypertrophy reveals both calcium-dependent and calcium-independent/RhoA-dependent calcineurin activation and NFAT nuclear translocation.

Leptin, a product of the obesity gene, has been shown to produce cardiac hypertrophy. Although leptin's mechanism of action is poorly understood activation of the RhoA/ROCK pathway has been proposed as a contributing mechanism. The Ca(2+)-dependent phosphatase calcineurin plays a critical role in the hypertrophic program although it is not known whether leptin can activate this signaling pathway or whether there is a relationship between RhoA activation and calcineurin.

The obesity-related peptide leptin sensitizes cardiac mitochondria to calcium-induced permeability transition pore opening and apoptosis.

The obesity-related 16 kDa peptide leptin is synthesized primarily in white adipocytes although its production has been reported in other tissues including the heart. There is emerging evidence that leptin may contribute to cardiac pathology especially that related to myocardial remodelling and heart failure. In view of the importance of mitochondria to these processes, the goal of the present study is to determine the effect of leptin on mitochondria permeability transition pore opening and the potential consequence in terms of development of apoptosis.

Sexual hormones: effects on cardiac and mitochondrial activity after ischemia-reperfusion in adult rats. Gender difference.

In this work we studied the influence of sex hormones on heart and mitochondrial functions, from adult castrated female and male, and intact rats. Castration was performed at their third week of life and on the fourth month animals were subjected to heart ischemia and reperfusion. Electrocardiogram and blood pressure recordings were made, cytokines levels were measured, histopathological studies were performed and thiobarbituric acid reactive species were determined.

Ginseng reverses established cardiomyocyte hypertrophy and postmyocardial infarction-induced hypertrophy and heart failure.

Background: A major challenge in the treatment of heart failure is the ability to reverse already-established myocardial remodeling and ventricular dysfunction, with few available pharmacological agents prescribed for the management of heart failure having demonstrated successful reversal of the remodeling and hypertrophic processes. North American ginseng (Panax quinquefolius) has previously been shown to effectively prevent cardiomyocyte hypertrophy and heart failure. Here, we determined whether North American ginseng can reverse established cardiomyocyte hypertrophy in cultured myocytes as well as hypertrophy and left ventricular dysfunction in experimental heart failure secondary to coronary artery occlusion.

A CRAC-like motif in BAX sequence: relationship with protein insertion and pore activity in liposomes.

Several proteins that interact with cholesterol have a highly conserved sequence, corresponding to the cholesterol recognition/interaction amino acid consensus. Since cholesterol has been proposed to modulate both oligomerization and insertion of the pro-apoptotic protein BAX, we investigated the existence of such a motif in the BAX sequence. Residues 113 to 119 of the recombinant BAX α5-helix, LFYFASK, correspond with the sequence motif described for the consensus pattern, -L/V-(X)(1-5)-Y-(X)(1-5)-R/K.

Octylguanidine ameliorates the damaging effect of mercury on renal functions.

Mercurials are known to induce morphological and functional modifications in kidney. The protective effect of octylguanidine on the injury induced by Hg(2+) on renal functions was studied. Octylguanidine administered at a dose of 10 mg/kg body weight prevented the damage induced by Hg(2+) administration at a dose of 3 mg/kg body weight.

Protective effect of sulforaphane against cisplatin-induced mitochondrial alterations and impairment in the activity of NAD(P)H: quinone oxidoreductase 1 and γ glutamyl cysteine ligase: studies in mitochondria isolated from rat kidney and in LLC-PK1 cells.

This work was designed to further study the mechanism by which sulforaphane (SFN) exerts a renoprotective effect against cisplatin (CIS)-induced damage. It was evaluated whether SFN attenuates the CIS-induced mitochondrial alterations and the impairment in the activity of the cytoprotective enzymes NAD(P)H: quinone oxidoreductase 1 (NQO1) and γ glutamyl cysteine ligase (γGCL). Studies were performed in renal epithelial LLC-PK1 cells and in isolated renal mitochondria from CIS, SFN or CIS+SFN treated rats.

Reduced capacity of Ca²+ retention in liver as compared to kidney mitochondria. ADP requirement.

Ca²+ loading in mitochondria promotes the opening of a non-selective transmembrane pathway. Permeability transition is also associated with the interaction of cyclophilin D at the internal surface of the non-specific transmembrane pore. This interaction is circumvented by cyclosporin A and ADP.

Cyclosporin A inhibits UV-radiation-induced membrane damage but is unable to inhibit carboxyatractyloside-induced permeability transition.

This work was undertaken to gain further information on the chemical characteristics of the membrane entity involved in the formation of the nonspecific pore. Mitochondria were subjected to oxidative stress by exposure to UV radiation. The results indicate that ultraviolet C radiation induces structural modifications in the adenine nucleotide translocase that lead to membrane permeability transition.

Induction of mitochondrial permeability transition by the DNA-intercalating cationic dye ethidium bromide.

This work shows that the DNA cationic probe, ethidium bromide (EtBr), induces the transition from selective to non-selective mitochondrial permeability. This statement is based on the findings, indicating: (i) EtBr induced the release of accumulated Ca(2+) through a mechanism sensitive to cyclosporin A and octylguanidine; (ii) EtBr induced the release of cytochrome c and (iii) EtBr induced mitochondrial swelling. Interestingly, mersalyl inhibited, in a non-competitive fashion, EtBr uptake, which would indicate that the uptake may be carried out through a protein membrane system.