Ácidos graxos de cadeia curta e seu papel na patofisiologia do hospedeiro

Os ácidos graxos de cadeia curta (AGCC) são metabólitos resultantes da fermentação realizada pela microbiota intestinal e que possuem impacto relevante para a fisiologia do hospedeiro. Os principais AGCC microbianos são o butirato, acetato e propionato, e suas funções são decorrentes da sinalização gerada a partir da ligação com receptores acoplados à proteína G (GPCR) e modulação epigenética de histona deacetilases (HDAC). Os AGCC são absorvidos pelo epitélio intestinal e são utilizados como um importante substrato energético para os colonócitos, com um destaque para o butirato. O que não é consumido pelo epitélio intestinal entra na circulação sanguínea pelos capilares intestinais e migram rumo à veia porta, onde atingem o fígado. O propionato é utilizado como substrato para a gliconeogênese hepática, e dessa forma o acetato se torna o AGCC em maior concentração na circulação sanguínea após passar pelo fígado. Por meio da circulação, os AGCC então atingem o coração, de onde são distribuídos para os tecidos periféricos e para o cérebro, onde o acetato possui capacidade de atravessar a barreira hematoencefálica. A cada parte do organismo no qual os AGCC entram em contato, há a ativação de série de efeitos que são capazes de alterar a fisiologia do hospedeiro, podendo assim estar associados a patologias relacionadas a esses órgãos. Com o rápido desenvolvimento de tecnologias de sequenciamento em massa associadas a análises bioinformáticas mais robustas, pode-se ter maior compreensão acerca da microbiota, seus metabólitos e os mecanismos envolvidos na sua interação com o hospedeiro. Entretanto, novos estudos devem ser feitos para aprofundar o conhecimento acerca dos AGCC e aplicá-lo em prol do benefício humano.Short-chain fatty acids (SCFAs) are end products of gut bacteria and are known to impact host physiology significantly. The main microbial SCFA are butyrate, acetate, and propionate. Their functions are due the signaling generated from G protein-coupled receptors (GPCRs) and epigenetic modulation of histone deacetylases (HDACs). SCFAs are absorbed by the intestinal epithelium and are used as a crucial energetic substrate for colonocytes, emphasizing butyrate. SCFAs not consumed by the epithelium go to the bloodstream through intestinal capillaries and migrates towards the portal vein, where they reach the liver. Propionate is known as a substrate for hepatic gluconeogenesis, and then acetate becomes the SCFA find in greater concentrations in the bloodstream after passing through the liver. Through circulation, SCFAs can reach the heart and then are distributed to peripheral tissues and finally to the brain, where acetate can cross the blood-brain barrier (BBB). At each one of these organs, SCFAs can activate a series of effects that can influence the host’s physiology and may be associated with pathologies related to these organs. With the accelerated development of mass sequencing technologies in association with bioinformatics analysis, we can understand more and more about the microbiota, its metabolites, and mechanisms involved in microbiota-host interaction. However, much remains to be discovered for SCFAs to be applied for human benefit in novel therapeutic strategies

Intranasal HSP70 administration protects against dopaminergic denervation and modulates neuroinflammatory response in the 6-OHDA rat model

HSP70 is one of the main molecular chaperones involved in the cellular stress response. Besides its chaperone action, HSP70 also modulates the immune response. Increased susceptibility to toxic insults in intra- and extracellular environments has been associated with insufficient amounts of inducible HSP70 in adult neurons. On the other hand, exogenous HSP70 administration has demonstrated neuroprotective effects in experimental models of age-related disorders. In this regard, this study investigated the effects of exogenous HSP70 in an animal model of dopaminergic denervation of the nigrostriatal axis. After unilateral intrastriatal injection with 6-hydroxydopamine (6-OHDA), the animals received purified recombinant HSP70 through intranasal administration (2 μg/rat/day) for 15 days. Our results indicate a neuroprotective effect of intranasal HSP70 against dopaminergic denervation induced by 6-OHDA. Exogenous HSP70 improved motor impairment and reduced the loss of dopaminergic neurons caused by 6-OHDA. Moreover, HSP70 modulated neuroinflammatory response in the substantia nigra, an important event in Parkinson’s disease pathogenesis. Specifically, HSP70 treatment reduced microglial activation and astrogliosis induced by 6-OHDA, as well as IL-1β mRNA expression in this region. Also, recombinant HSP70 increased the protein content of HSP70 in the substantia nigra of rats that received 6-OHDA. These data suggest the neuroprotection of HSP70 against dopaminergic neurons damage after cellular stress. Finally, our results indicate that HSP70 neuroprotective action against 6-OHDA toxicity is related to inflammatory response modulation