Biology subjects

Santos, K. B. N. H.

Publications and source records attributed to Santos, K. B. N. H..

2 recordsLinked to original sources

bioRxiv2023

Pathological beige remodeling induced by cancer cachexia depends on the disease severity and involves mainly the trans-differentiation of mature white adipocytes

In cancer associated cachexia (CAC), white adipose tissue undergoes morphofunctional and inflammatory changes that lead to tissue dysfunction and remodeling. In addition to metabolic changes in white adipose tissues (WAT), adipose tissue atrophy has been implicated in several clinical complications and poor prognoses associated with cachexia. Adipocyte atrophy may be associated with increased beige remodeling in human CAC as evidenced by the "beige remodeling" observed in preclinical models of CAC. Even though beige remodeling is associated with CAC-induced WAT dysfunction, there are still some open questions regarding their cellular origins. In this study, we investigated the development of beige remodeling in CAC from a broader perspective. In addition, we used a grading system to identify the scAT as being affected by mice weight loss early and intensely. Using different in vitro and ex-vivo techniques, we demonstrated that Lewis LLC1 cells can induce a switch from white to beige adipocytes, which is specific to this type of tumor cell. During the more advanced stages of CAC, beige adipocytes are mainly formed from the transdifferentiation of cells. According to our results, humanizing the CAC classification system is an efficient approach to defining the onset of the syndrome in a more homogeneous manner. Pathological beige remodeling occurred early in the disease course and exhibited phenotypic characteristics specific to LLC cells secretomes. Developing therapeutic strategies that recruit beige adipocytes in vivo may be better guided by an understanding of the cellular origins of beige adipocytes emitted by CAC.

cell biology↗

bioRxiv2020

FUNGAL DYSBIOSIS CORRELATES WITH THE DEVELOPMENT OF TUMOUR-INDUCED CACHEXIA IN MICE

Cachexia (CC) is a devastating metabolic syndrome associated with a series of underlying diseases that greatly affects life quality and expectancy among cancer patients. Studies involving mouse models, in which CC was induced through inoculation with tumor cells, originally suggested the existence of a direct correlation between the development of this syndrome and changes in the relative proportions of several bacterial groups present in the digestive tract. However, these analyses have focus solely on the characterization of bacterial dysbiosis, ignoring the possible existence of changes in the relative populations of fungi, during the development of CC. Thus, the present study sought to expand such analyses, by characterizing changes that occur in the gut fungal population (mycobiota) of mice, during the development of cancer-induced cachexia. Our results confirm that cachectic animals display significant differences in their gut mycobiota, when compared to healthy controls. Moreover, identification of dysbiotic fungi showed remarkable consistency across successive levels of taxonomic hierarchy. Many of these fungi have also been associated with dysbioses observed in a series of gut inflammatory diseases, such as obesity, Colorectal Cancer (CRC), Myalgic Encephalomyelitis (ME) and Inflammatory Bowel Disease (IBD). Nonetheless, the CC-associated dysbiosis seems to be unique, presenting features observed in both obesity (reduced proportion of Mucoromycota) and CRC/ME/IBD (increased proportions of Sordariomycetes, Saccharomycetaceae and Malassezia). One species of Mucoromycota (Rhyzopus oryzae) stands out as a promising probiotic candidate in adjuvant therapies, aimed at treating and/or preventing the development of CC.

microbiology↗