The impact of obesity in the cardiac lipidome and its consequences in the cardiac damage observed in obese rats / El impacto de la obesidad sobre el lipidoma cardiaco y sus consecuencias en el daño cardiaco en ratas obesas

Aims: To explore the impact of obesity on the cardiac lipid profile in rats with diet-induced obesity, as well as to evaluate whether or not the specific changes in lipid species are associated with cardiac fibrosis. Methods: Male Wistar rats were fed either a high-fat diet (HFD, 35% fat) or standard diet (3.5% fat) for 6 weeks. Cardiac lipids were analyzed using by liquid chromatography-tandem mass spectrometry. Results: HFD rats showed cardiac fibrosis and enhanced levels of cardiac superoxide anion (O2), HOMA index, adiposity, and plasma leptin, as well as a reduction in those of cardiac glucose transporter (GLUT 4), compared with control animals. Cardiac lipid profile analysis showed a significant increase in triglycerides, especially those enriched with palmitic, stearic, and arachidonic acid. An increase in levels of diacylglycerol (DAG) was also observed. No changes in cardiac levels of diacyl phosphatidylcholine, or even a reduction in total levels of diacyl phosphatidylethanolamine, diacyl phosphatidylinositol, and sphingomyelins (SM) was observed in HFD, as compared with control animals. After adjustment for other variables (oxidative stress, HOMA, cardiac hypertrophy), total levels of DAG were independent predictors of cardiac fibrosis while the levels of total SM were independent predictors of the cardiac levels of GLUT 4. Conclusions: These data suggest that obesity has a significant impact on cardiac lipid composition, although it does not modulate the different species in a similar manner. Nonetheless, these changes are likely to participate in the cardiac damage in the context of obesity, since total DAG levels can facilitate the development of cardiac fibrosis, and SM levels predict GLUT4 levels (AU)

Objetivos: Explorar el impacto de la obesidad sobre el perfil lipídico cardiaco en ratas con obesidad inducida por dieta. Se evaluó, además, si estos cambios se asocian con fibrosis cardiaca. Métodos: Ratas macho Wistar fueron alimentadas con una dieta con alto contenido en grasa (HFD; 35% grasa) o con una dieta estándar (3,5% grasa) durante 6 semanas. El análisis del lipidoma cardiaco se realizó mediante cromatografía líquida en tándem con espectrofotometría de masas. Resultados: Las ratas HFD presentaron fibrosis cardiaca, estrés oxidativo y un aumento en el índice HOMA, adiposidad y los niveles circulantes de leptina así como una reducción en los niveles cardiacos del transportador de glucosa (GLUT 4) en comparación con las ratas controles. El análisis del lipidoma cardiaco mostró un aumento de los niveles de triglicéridos especialmente los que contenían ácido palmítico, esteárico o araquidónico, un incremento en los de diacilglicerol (DAG) aunque no cambios en los de diacilfosfatidilcolina y una reducción en los de diacilfosofatidiletanolamina, diacilfosfatidilinositol o de esfingomielinas (SM) en las ratas HFD en comparación con las control. Después del ajuste por otras variables (estrés oxidativo, hipertrofia cardiaca, índice HOMA), los niveles de DAG fueron predictores independientes de fibrosis cardiaca mientras que los de SM fueron de los de niveles de GLUT4. Conclusiones: La obesidad ejerce un impacto importante sobre el lipidoma cardiaco. Estos cambios parecen participar en el daño cardiaco en el contexto de la obesidad ya que los niveles de DAG podrían facilitar el desarrollo de fibrosis miocárdica y los de SM los de GLUT 4 (AU)

Endothelial dysfunction of rat coronary arteries after exposure to low concentrations of mercury is dependent on reactive oxygen species.

BACKGROUND AND PURPOSE: Exposure to mercury is known to increase cardiovascular risk but the underlying mechanisms are not well explored. We analysed whether chronic exposure to low mercury doses affects endothelial modulation of the coronary circulation. EXPERIMENTAL APPROACH: Left coronary arteries and hearts from Wistar rats treated with either HgCl(2) (first dose 4.6 µg·kg(-1) , subsequent doses 0.07 µg·kg(-1) day(-1) , 30 days) or vehicle were used. Endothelial cells from pig coronary arteries incubated with HgCl(2) were also used. KEY RESULTS: Mercury treatment increased 5-HT-induced vasoconstriction but reduced acetylcholine-induced vasodilatation. It also reduced nitric oxide (NO) production and the effects of NO synthase inhibition with L-NAME (100 µmol·L(-1) ) on 5-HT and acetylcholine responses. Superoxide anion production and mRNA levels of NOX-1 and NOX-4 were all increased. The superoxide anion scavenger tiron (1 mmol·L(-1)) reduced 5-HT responses and increased acetylcholine responses only in vessels from mercury-treated rats. In isolated hearts from mercury-treated rats, coronary perfusion and diastolic pressure were unchanged, but developed isovolumetric systolic pressure was reduced. In these hearts, L-NAME increased coronary perfusion pressure and diastolic pressure while it further reduced developed systolic pressure. CONCLUSIONS AND IMPLICATIONS: Chronic exposure to low doses of mercury promotes endothelial dysfunction of coronary arteries, as shown by decreased NO bioavailability induced by increased oxidative stress. These effects on coronary function increase resistance to flow, which under overload conditions might cause ventricular contraction and relaxation impairment. These findings provide further evidence that mercury, even at low doses, could be an environmental risk factor for cardiovascular disease.

Serotonergic innervation of the inner ear: is it involved in the general physiological control of the auditory receptor?

The auditory pathway of mammals is composed of two complementary ascending afferent and descending efferent independent systems. The brainstem nuclei and cochlear projections for these systems are now well-known. In addition, a highly conspicuous distribution for serotonergic fibers was recently reported. This study focused on these serotonergic fibers and their neurons of origin. We identified several different types of serotonergic brainstem neurons surrounding the superior olivary complex and around the periolivary nuclei. Even though the 5-hydroxytryptamine (5-HT) efferent cochlear innervation originates in the periolivary area of the superior olivary complex system projecting to the cochlea, it is not involved in the transduction of pure tones during auditory processing. However, recent findings, after cochlear blockade of serotonin transporters, strongly suggested that this neuroactive substance has an important turnover within the auditory receptor. The presence of a conspicuous peripheral nerve distribution together with a particular brainstem origin could define a complex role for this innervation. Therefore, 5-HT fibers projecting to the cochlea might be involved, as in other parts of the auditory pathway, in alertness, attention, control of sleep or wakefulness cycles, and state of urgency prior to the transduction processing at the auditory receptor. A lack, or reduction, of the function of these fibers could result in pathological alterations.

Biochemical evidence for the presence of serotonin transporters in the rat cochlea.

Cochlear serotonergic innervation is constituted by efferent fibers projecting both to the area below the inner and the outer hair cells. Previous detection of serotonin (5-HT) metabolites and 5-HT receptor mRNAs suggests the existence of serotonergic synaptic activity in the cochlea. The present study explores this possibility through the effect of 6-nitroquipazine (6-NQ), a 5-HT selective reuptake inhibitor, on the basal turnover of 5-HT. The concentrations of 5-HT and its metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) were quantified by high performance liquid chromatography with electrochemical detection in blood-free cochleae of rats treated with 6-NQ or saline and kept under silent conditions. Treatment with 6-NQ induced a significant increase of the cochlear concentration of 5-HT and a significant reduction of 5-HIAA concentration with respect to saline treatment. These findings could indicate that 6-NQ induced the blockade of the 5-HT selective reuptake to the cochlear serotonergic fibers. This suggests that plasma membrane 5-HT transporters are present in cochlear serotonergic fibers. Even though the role of serotonergic innervation on cochlear physiology remains unknown, the existence of cochlear serotonergic synaptic activity is strongly supported by present contributions.