Biology subjects

Oliveira, M. P.

Publications and source records attributed to Oliveira, M. P..

4 recordsLinked to original sources

bioRxiv2023

Vagus nerve mediated liver-brain axis is a major regulator of the metabolic landscape in the liver

BackgroundThe liver serves as a major energetic reservoir for other tissues and its metabolic function is controlled by humoral and neural factors. The vagus nerve innervating the gastrointestinal tract plays an important role in regulating peripheral metabolism and energy expenditure. Although the liver receives vagus nerve fibers, the impact of this circuitry in the regulation of hepatic metabolism is still poorly understood. MethodsHerein, we used a combination of quantitative proteomics and in vivo imaging techniques to investigate the impact of the vagus nerve on liver metabolism. ResultsVagus nerve shapes the metabolic framework of the liver, as surgical ablation (vagotomy; VNX) of this circuitry led to a significant alteration of the hepatic proteome landscape. Differential protein expression and pathway enrichment analyses showed that glycolytic and fatty acid biosynthesis were increased following VNX, whereas {beta}-oxidation was decreased. This metabolic shift facilitated lipid accumulation in hepatocytes. Furthermore, VNX worsened liver steatosis following high-carbohydrate or high-fat dietary challenges. ConclusionsThis study describes the liver-brain axis mediated by the vagus nerve as an important regulator of the hepatic metabolic landscape. HighlightsO_LIVagus nerve is a novel regulator of the hepatic metabolic landscape. C_LIO_LIAblation of vagus nerve neural circuit by vagotomy resulted in a metabolic shift towards glycolysis and fatty acid biosynthesis. C_LIO_LILipid accumulation was increased in vagotomized mice fed with a standard diet. C_LIO_LILiver steatosis was increased following dietary challenges with high-carbohydrate or high-fat diets. C_LIO_LIVagus nerve can be a promising new target for NAFLD treatment. C_LI

physiology↗

bioRxiv2023

Activation of innate immunity selectively compromises mitochondrial complex I, proline oxidation and flight activity in the major arbovirus vector Aedes aegypti

Aedes aegypti females are natural vectors of important arboviruses such as Dengue, Zika, and yellow fever. Mosquitoes activate innate immune response signaling pathways upon infection, as a resistance mechanism to fight pathogens and limit their propagation. Despite the beneficial effects of immune activation for insect vectors, phenotypic costs ultimately affect their fitness. However, the underlying mechanisms that mediate these fitness costs remain poorly understood. Given the high energy required to mount a proper immune response, we hypothesized that systemic activation of innate immunity would impair flight muscle mitochondrial function, compromising tissue energy demand and flight activity. Here, we investigated the dynamic effects of activation of innate immunity by intra-thoracic zymosan injection on A. aegypti flight muscle mitochondrial metabolism. Zymosan injection significantly increased defensin expression in fat bodies in a time-dependent manner that compromised flight activity. Although oxidant levels in flight muscle were hardly altered, ATP-linked respiratory rates driven by mitochondrial pyruvate+proline oxidation were significantly reduced at 24h upon zymosan injection. Oxidative phosphorylation coupling was preserved regardless of innate immune response activation along 24h. Importantly, rotenone-sensitive respiration and complex I-III activity were specifically reduced 24h upon zymosan injection. Also, loss of complex I activity compromised ATP-linked and maximal respiratory rates mediated by mitochondrial proline oxidation. Finally, the magnitude of innate immune response activation negatively correlated with respiratory rates, regardless of the metabolic states. Collectively, we demonstrate that activation of innate immunity is strongly associated with reduced flight muscle complex I activity with direct consequences to mitochondrial proline oxidation and flight activity. Remarkably, our results indicate a trade-off between dispersal and immunity exists in an insect vector, underscoring the potential consequences of disrupted flight muscle mitochondrial energy metabolism to arbovirus transmission.

biochemistry↗

bioRxiv2023

Heme exporter FLVCR regulates mitochondrial biogenesis and redox balance in the hematophagous insect Rhodnius prolixus

Heme is a prosthetic group of proteins involved in vital physiological processes in aerobic organisms. It participates in redox reactions crucial for cell metabolism due to the variable oxidation state of its central iron atom. However, excessive heme can be cytotoxic due to its prooxidant properties. Therefore, the control of intracellular heme levels ensures the survival of organisms, especially those that deal with high concentrations of heme during their lives, such as hematophagous insects. The feline leukemia virus C receptor (FLVCR) is a membrane protein responsible for heme transport in mammalian cells. In our study, we found that RpFLVCR serves as a heme exporter in the midgut of the hematophagous insect Rhodnius prolixus, a vector for Chagas disease. Silencing RpFLVCR decreased hemolymphatic heme levels and increased the levels of intracellular dicysteinyl-biliverdin, a product of R. prolixus heme degradation, indicating heme retention inside midgut cells. FLVCR silencing led to increased expression of heme oxygenase (HO), ferritin, and mitoferrin mRNAs while downregulating the iron importers Malvolio 1 and 2. In contrast, HO gene silencing increased FLVCR and Malvolio expression and downregulated ferritin, revealing crosstalk between heme degradation/export and iron transport/storage pathways. Furthermore, RpFLVCR silencing strongly increased oxidant production and lipid peroxidation, reduced cytochrome c oxidase activity and activated mitochondrial biogenesis, effects not observed in RpHO-silenced insects. These data support FLVCR function as a heme exporter, playing a pivotal role in heme/iron metabolism and maintenance of redox balance, especially in an organism adapted to face extremely high concentrations of heme.

biochemistry↗

bioRxiv2020

A cytokine network balance influences the fate of Leishmania (Viannia) braziliensis infection in a cutaneous leishmaniasis hamster model

The golden hamster is a suitable model for studying cutaneous leishmaniasis (CL) due to Leishmania (Viannia) braziliensis. Immunopathological mechanismsare wellstablished inthe L. (L.) major-mouse model, in which IL-4 instructs a Th2 response towards progressive infection. In the present study, we evaluatedthe natural history of L. braziliensis infection from its first stagesup to lesion establishment, with the aim ofidentifyingimmunological parameters associated with the disease outcome and parasitismfate. To this end, hamsters infected with 104, 105,or 106 promastigoteswere monitored duringthe first hours (4h, 24h), early (15, 30 days) and late (50 days) post-infection (pi) phases. Cytokines, iNOS and arginasegene expression were quantified in the established lesions by RT-PCR. Compared to the 105 or 106 groups, 104animals presented lower lesions sizes, less tissue damage,and lower IgG levels. Basal gene expression in normal skin was high for TGF-{beta}, and intermediary for TNF, IL-6, and IL-4.At 4hpi, no cytokine induction was observed in the 104 group, while an upregulation of IL-6, IL-10, and IL-4 was observed in the 106 group. At 15dpi, lesion appearance was accompanied byan increasedexpression of all assessed cytokines, markedly in the 105 and 106 groups. Upregulation of all investigated cytokines was observed in the late phase, although less expressive in the 104 group. IFN-{gamma} was the depending variable influencing tissue damage, while IL-6 was associatedto parasite load. The network correlating gene expression and clinical and laboratorial parameters indicated inoculum-independent associations at 15 and 30dpi.A strong positive network correlation was observed in the 104 group, but not in the105 or 106 groups. In conclusion, IL-4, IL-6, IL-10, and TGF-{beta} are linkedto L. braziliensisprogression. However, a balanced cytokine network is the key for an immune response able to reduce the ongoing infection and reduce pathological damage.

immunology↗