Biology subjects

Pires, V.

Publications and source records attributed to Pires, V..

3 recordsLinked to original sources

bioRxiv2026

Postprandial hypertriglyceridemia activates microglia to promote satiety via an ASC dependent signaling.

Reactive microglia are commonly considered neurotoxic and detrimental for brain functioning. Chronic consumption of a high-fat diet strongly activates microglia, disrupts the central control of energy metabolism, contributes to obesity, and promotes cognitive decline. In this study we report an unexpected beneficial function of microglia reaction at the time scale of a meal, whereby they promote satiety in a macronutrient-dependent manner. We show that murine microglia react to ingested dietary fat within three hours. Specifically, postprandial hypertriglyceridemia induced microglial hyper-ramification alongside with a transcriptional reprogramming promoting communication with neurons. This effect occurs in discrete brain areas, including the hypothalamus and the brainstem, which control hunger. Remarkably, microglia-specific genetic ablation of Apoptosis-associated Speck-like protein containing a CARD (named ASC), a master regulator of metabolism, immune function and cell shape, profoundly alters satiety following high-fat food consumption. These results reveal that microglia engage an immune signaling pathway to rapidly alert the neural circuits and activate an anorectic response that limits overconsumption of dietary fat. Unexpectedly, this regulatory process is sexually dimorphic, present in males only. Furthermore, we found that the postprandial microglial reaction is bypassed during obesity, providing a new therapeutic target to treat maladaptive eating disorders.

neuroscience↗

bioRxiv2023

Mob4 is essential for spermatogenesis in Drosophila melanogaster

Gamete formation is essential for sexual reproduction in metazoans. In males, spermatogenesis gives rise to interconnected spermatids that have to differentiate and individualize into mature sperm. In Drosophila melanogaster, individualization of spermatids requires the formation of individualization complexes that synchronously move along the sperm bundles. Here, we show that Mob4, a member of the Mps-one binder family, is essential for male fertility but has no detectable role on female fertility. We describe the function of Mob4 during spermatid individualization, showing that Mob4 is required for proper axonemal structure and that the loss of Mob4 leads to male sterility associated with defective spermatid individualization and absence of mature sperm in the seminal vesicles. Transmission electron micrographs of Mob4RNAi developing spermatids revealed defects in axoneme structure and abnormal mitochondria biogenesis. Importantly, we find that male fertility is impaired upon depletion of other STRIPAK components, suggesting that Mob4 acts through STRIPAK to support spermiogenesis. As we show that expression of the human Mob4 gene effectively rescues all phenotypes of Mob4 downregulation, the gene is not only evolutionary but also functionally conserved. We propose that Mob4 plays a role in regulating the microtubule- and actin-cytoskeleton during spermatogenesis. This study advances our understanding of male infertility by uncovering Mob4 as a novel gene required for sperm individualization.

developmental biology↗

bioRxiv2019

RNase H1 and H2 are differentially regulated to eliminate RNA-DNA hybrids

RNA-DNA hybrids are tightly regulated to ensure genome integrity. The RNase H enzymes, RNase H1 and H2, contribute to chromosomal stability through the removal of RNA-DNA hybrids. Loss of RNase H2 function is implicated in human diseases of the nervous system and cancer. To better understand RNA-DNA hybrid dynamics, we have focused on elucidating the regulation of the RNase H enzymes themselves. Using yeast as a model system, we demonstrate that RNase H1 and H2 are controlled in different manners. RNase H2 is regulated in a strict cell cycle dependent manner, both in terms of its R-loop removal, and ribonucleotide excision repair functions. RNase H1, however, can function independent of cell cycle stage to remove R-loops, but appears to become activated in response to high R-loop loads. These results provide us with a more complete understanding of how and when RNA-DNA hybrids are acted upon by the RNase H enzymes.

molecular biology↗