DANIELLE CRISTINA FONSECA CANDIAN
Projetos de Pesquisa
Unidades Organizacionais
LIM/35 - Laboratório de Nutrição e Cirurgia Metabólica do Aparelho Digestivo, Hospital das Clínicas, Faculdade de Medicina
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- Genetic reprogramming of rHemnant duodenum may contribute to type 2 diabetes improvement after Roux-en-Y gastric bypass(2022) SALA, Priscila; MACHADO, Natasha Mendonca; TORRINHAS, Raquel Susana Matos de Miranda; FONSECA, Danielle C.; FERREIRA, Beatriz A. M.; ISHIDA, Robson Kiyoshi; GUARDA, Ismael Francisco Mota Siqueira; MOURA, Eduardo Guimaraes Hourneaux de; SAKAI, Paulo; SANTO, Marco Aurelio; HEYMSFIELD, Steven B.; CORREA-GIANNELLA, Maria Lucia; WAITZBERG, Dan LinetzkyObjectives: Type 2 diabetes control occurs within a few days after Roux-en-Y gastric bypass (RYGB) and might be related to intestinal adaptation to the new anatomic arrangement. The aim of this study was to evaluate the intestinal transcriptome response to RYGB and its correlation with markers of glycemic homeostasis. Methods: Global transcriptomic analyses performed by microarray technique were conducted in intestinal biopsies collected from adult women with obesity (N = 20) and T2D before and 3 mo after RYGB. Clinical and biochemical markers of glycemic homeostasis were also evaluated. At 1-y postoperative, patients were clas-sified as responsive (R) or non-responsive (NR) to complete T2D remission according to the American Diabe-tes Association criteria. Intestinal differentially expressed genes (DEGs) were analyzed separately in the two groups, validated by reverse transcription quantitative polymerase chain reaction, and applied in functional enrichment and canonical pathway analysis. Spearman correlations between clinical and biochemical varia-bles with DEGs were conducted. Twelve patients were classified as R and displayed 62 (duodenum), 241 (jejunum), and 63 (ileum) DEGs. Results: Eight of the patients with DEGs presented very strong or strong positive correlations with glycemia or glycated hemoglobin. Duodenal changes of genes involved in the LXR/RXR pathway were more likely to be associated with T2D. Conclusion: In obese women, complete remission of T2D after RYGB might include intestinal transcriptomic changes that suggest a potential role of intracellular cholesterol and lipid homeostasis on glucose control.(c) 2022 Elsevier Inc. All rights reserved.
- Roux-en-Y gastric bypass affects the expression of genes related to the intestinal folate metabolism pathway in obese women(2023) FERREIRA, Beatriz de Azevedo Muner; FONSECA, Danielle Cristina; SALA, Priscila; ALVES, Juliana Tepedino Martins; PRUDENCIO, Ana Paula Aguiar; MACHADO, Natasha Mendonca; MARQUES, Mariane; BARCELOS, Samira; ISHIDA, Robson Kiyoshi; GUARDA, Ismael Francisco Mota Siqueira; MOURA, Eduardo Guimaraes Hourneaux De; SAKAI, Paulo; SANTE, Marco Aurelio; TORRINHAS, Raquel Susana Matos de Miranda; WAITZBERG, Dan LinetzkyObjectives: Roux-en-Y gastric bypass (RYGB) promotes sustained weight loss, and the resulting new gastroin-testinal anatomy can contribute to nutritional depletions. Folate deficiency is one of the most frequently observed nutritional deficiencies after RYGB. The aim of this study was to assess whether RYGB affects the expression of genes related to the intestinal folate metabolism pathway as an additional molecular mecha-nism contributing to its postoperative deficiency. Methods: Biopsies from the duodenum, jejunum, and ileum of 20 obese women were collected before and 3 mo after RYGB. The expression of genes involved in intestinal folate metabolism was assessed by microarray and reverse transcriptase polymerase chain reaction (RT-qPCR). Folate intake (7-d food record) and plasma levels (electrochemiluminescence) also were measured. Results: Compared with the preoperative phase, transcriptomic alterations were observed in all intestinal segments studied after RYBG, mainly marked by decreased expression of genes encoding folate transporters/ receptors and increased expression of genes involved in folate biosynthesis (P < 0.05). Reduced folate intake and plasma folate levels were also observed simultaneously (P < 0.05). Plasma folate concentrations corre-lated inversely with intestinal FOLR2 and SHMT2 genes (P < 0.001). Conclusion: The present findings suggested that impaired expression of genes related to intestinal folate metabolism may contribute to the early systemic deficiency after RYGB and highlight a potential transcrip-tomic reprogramming of the intestine in response to RYGB to compensate for folate depletion induced by this surgical technique.(c) 2023 Elsevier Inc. All rights reserved.
- SARS-CoV-2 infection, gut dysbiosis, and heterogeneous clinical results of hydroxychloroquine on COVID-19 therapy & mdash;Is there a link?(2021) BALMANT, Bianca D.; TORRINHAS, Raquel S.; ROCHA, Ilanna M.; FONSECA, Danielle C.; FORMIGA, Francisco F. C.; BONFA, Eloisa S. D. O.; BORBA, Eduardo F.; WAITZBERG, Dan L.Clinical manifestations of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can include gastrointestinal signals and symptoms. Individuals with previous clinical conditions that usually enroll gut dysbiosis have been identified as being at high risk to develop more severe infectious phenotypes. Actually, intestinal dysbiosis has been observed in infected patients and potentially linked to systemic hyper-inflammation. These observations suggest that a previous gut dysbiosis may be aggravated by SARS-CoV-2 infection and related to progression of the coronavirus disease 2019 (COVID-19) into more severe stages. While COVID-19 & rsquo;s pathophysiology is not fully understood, it seems relevant to consider the interactions of candidate therapeutic drugs with the host, gut microbiota, and SARS-CoV-2. Here we summarize scientific evidence supporting the potential relevance of these interactions and suggest that unfavorable clinical data on hydroxychloroquine administration in COVID-19 may have been influenced by the dose provided and its impact on gut dysbiosis. The proposition is based on preliminary data on gut microbiota composition from individuals with inactive systemic lupus erythematosus under exclusive continuous hydroxychloroquine treatment, displaying a direct correlation between drug doses and markers typically associated with gut dys-biosis.
- Intestinal expression of toll-like receptor gene changes early after gastric bypass surgery and association with type 2 diabetes remission(2020) SALA, Priscila; TORRINHAS, Raquel Susana Matos de Miranda; FONSECA, Danielle C.; MACHADO, Natasha Mendonca; SINGER, Joelle; SINGER, Pierre; RAVACCI, Graziela Rosa; BELARMINO, Giliane; FERREIRA, Beatriz A. M.; MARQUES, Mariane; ISHIDA, Robson Kiyoshi; GUARDA, Ismael Francisco Mota Siqueira; MOURA, Eduardo Guimaraes Hourneaux de; SAKAI, Paulo; SANTO, Marco Aurelio; SUNAGA, Daniele Yumi; HEYMSFIELD, Steven B.; BEZERRA, Daniele Pereira dos Santos; CORREA-GIANNELLA, Maria Lucia; WAITZBERG, Dan LinetzkyObjectives: Abnormal activation of toll-like receptors (TLRs) is observed in obese rodents and is correlated with local dysbiosis and increased gut permeability. These purported changes trigger systemic inflammation associated with obesity-related comorbidities, including type 2 diabetes (T2D). Roux-en-Y gastric bypass (RYGB) surgery is an effective treatment for severe obesity and known to induce changes in the gut microbiota and decrease systemic inflammation in humans. This study examined the intestinal expression of TLR-encoding genes in obese women (n = 20) treated with RYGB surgery and the relationship of these genes with T2D remission (T2Dr Methods: Intestinal biopsies were performed before and 3 months after RYGB surgery. Partial and complete T2Dr after 1 year was assessed using the American Diabetes Association criteria. Affymetrix Human GeneChip 1.0 ST array (microarray) and TaqMan assay (real-time quantitative polymerase chain reaction) were used to analyze intestinal gene expression, and associations with systemic markers of energy homeostasis were examined. Results: Patients experienced significant weight loss (P < 0.001) and altered gut TLR gene expression 3 months after surgery. The main effects were a reduction in jejunal TLR4 expression in patients with complete and partial T2Dr (P < 0.05). There was a postoperative decrease in jejunal TLR7 expression in patients with complete T2Dr that correlated inversely with high-density lipoprotein cholesterol and positively with triglyceride concentrations, but not with weight loss. Conclusions: RYGB-induced weight loss-independent changes in the expression of intestinal TLR-encoding genes in obese women and complete T2Dr that was correlated with systemic markers of energy homeostasis. The modulation of intestinal TLRs may mediate inflammatory mechanisms linked to T2Dr after RYGB surgery.