Desfechos clínico-metabólicos em indivíduos obesos na vigência de altas concentrações de proteínas de fase aguda

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmácia, Florianópolis, 2021.A obesidade é um problema de saúde, caracterizado por um estado inflamatório de baixa intensidade. O tecido adiposo, em ambiente obesogênico perde sua homeostase e passa a secretar citocinas pró-inflamatórias, principalmente interleucina 6 (IL-6), fator de necrose tumoral alfa (TNF-a) e a proteína quimioatraente dos monócitos 1 (MCP-1). A IL-6, especialmente, pode agir localmente ou no fígado desencadeando a produção de proteínas de fase aguda. A a-1 glicoproteína ácida (AGP) e a-1 antitripsina (AAT) são proteínas de fase aguda que podem ter suas concentrações elevadas devido ao processo inflamatório presente na obesidade. São proteínas com características anti-inflamatórias que possuem um importante papel imunomodulador e podem estar envolvidas na regulação da produção de citocinas pró-inflamatórias. Além disso, pertencem ao grupo de proteínas constituinte do GlycA, um novo marcador de inflamação associado a medidas de adiposidade. Dentro deste contexto, o objetivo do estudo foi determinar e comparar as concentrações séricas da AGP e AAT em grupo de indivíduos com obesidade (GO) e em indivíduos magros (controle, GC), além de comparar as concentrações destas proteínas nos períodos anterior e posterior à cirurgia bariátrica, relacionando com o perfil inflamatório destes pacientes. As determinações de AGP e AAT foram realizadas por método imunonefelométrico e as concentrações das citocinas, IL-6, TNF-a e a MCP-1, por ensaio imunoenzimático. Como resultados, foram observadas diferenças significativas entre o GO e o GC nas concentrações de AGP, AAT, MCP-1 e IL-6. As concentrações de AGP apresentaram relação com as concentrações de IL-6 no período pré-operatório. Reduções significativas nas concentrações de AGP e IL-6 foram observadas após um ano do procedimento cirúrgico. Melhora nos parâmetros bioquímicos relacionados ao metabolismo da glicose e de lipídios, redução na utilização de fármacos hipoglicemiantes e de algumas classes de fármacos utilizados para distúrbios do sistema cardiovascular, além do aumento da suplementação de vitaminas e minerais, foram outros achados importantes observados no seguimento dos pacientes após um ano da realização da cirurgia. Com base nestes achados foi possível concluir que a elevação da AGP parece ser resultado da inflamação do tecido adiposo, já que apenas a AGP estava relacionada com as concentrações de IL-6 e suas concentrações apresentaram redução após a perda de peso decorrente do procedimento cirúrgico. Além disso a cirurgia bariátrica foi capaz de promover melhora nos parâmetros bioquímicos e no perfil farmacoterapêutico.Abstract: Obesity is a health problem, characterized by a low-grade inflammatory state. The adipose tissue, in an obesogenic environment, loses its homeostasis and secretes pro-inflammatory cytokines, mainly interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-a) and the monocyte chemoattracting protein-1 (MCP-1). IL-6, in particular, can act locally or in the liver, triggering the production of acute-phase proteins. a-1 acid glycoprotein (AGP) and a-1 antitrypsin (AAT) are acute-phase proteins that may display high concentrations due to the inflammatory process present in obesity. They are proteins with anti-inflammatory properties with an immunomodulatory role, and evidence suggests their action in regulating pro-inflammatory cytokines? production. These proteins are two of the main constituents of GlycA, a new inflammation marker associated with measures of adiposity. Within this context, the study aimed to determine and compare the serum AGP and AAT levels in the patients with obesity (GO) and lean individuals (CG), comparing the concentrations of these proteins in the periods before and after bariatric surgery and connect to the inflammatory profile of these patients. Determinations of AGP and AAT were performed by an immunonephelometric method and the concentrations of cytokines, IL-6, TNF-a and MCP-1, by immunoenzymatic assay. As results, significant differences were observed between the GO and the CG in AGP, AAT, MCP-1 and IL-6 levels. AGP levels were related to IL-6 in the preoperative period. Significant reductions in AGP and IL-6 levels were observed after one year of the surgical procedure. Improvements in biochemical parameters related to glucose and lipid metabolism, reduction in the use of hypoglycemic drugs and some classes of drugs used for disorders of the cardiovascular system, in addition to increased vitamin and mineral supplementation, were other important findings observed in the follow-up of patients with obesity one year after surgery. Based on these findings, it was possible to conclude that the increase in AGP seems to be the result of inflammation of the adipose tissue, since only AGP was related to IL-6 concentrations. Its concentrations showed a reduction after weight loss resulting from the surgical procedure. Besides, bariatric surgery was able to promote improvement in biochemical parameters and pharmacotherapeutic profile

Anti-Saccharomyces cerevisiae (ASCA) in patients with severe obesity undergoing bariatric surgery: 12-month follow-up.

Severe obesity is linked to a low-grade inflammatory process due to enlarged adipose tissue, resulting in elevated pro-inflammatory cytokines. Bariatric surgery induces anatomical changes, causing intestinal inflammation marked by anti-Saccharomyces cerevisiae (ASCA) antibodies. This study aimed to assess ASCA IgG/IgA levels preoperatively and 12 months post-surgery, correlating them with systemic inflammation markers (IL-6, CRP, MCP-1). Participants (BMI > 35 kg/m2) were recruited in South Brazil. Severe obesity individuals showed elevated IL-6 (p = 0.002), CRP (p<0.0001), and MCP-1 (p<0.0001) compared to lean controls. ASCA IgA was significantly higher in severe obesity (p = 0.0019). Post-surgery, ASCA IgG/IgA significantly decreased (p = 0.0046 and p<0.0001), along with IL-6, MCP-1, and CRP, confirming weight loss and reduced inflammation. Hypertrophic adipose tissue, producing pro-inflammatory cytokines, associates with increased intestinal inflammation. Bariatric surgery-induced anatomical changes contribute to long-term weight loss and reduced systemic and intestinal inflammation

Drug binding and drug-drug interaction considerations in individuals with obesity before and after bariatric surgery: A retrospective cross-sectional study

Obesity impacts pharmacokinetic and pharmacodynamic parameters, changing the drug-binding state via plasma proteins, which is critical for drug effectiveness and toxicity. Albumin and α1-acid glycoprotein (AAG) are the two main proteins accountable for drug binding in humans. Previous studies have shown higher values of AAG in individuals with obesity, but the interference of AAG in the pharmacokinetics of drugs remains unclear. We, therefore, aimed to analyze the pharmacotherapeutic profile and interfering factors in patients undergoing bariatric surgery in the pre-operative period and after 12 months. A retrospective cross-sectional study design was conducted and serum AAG was determined, and potential drug-drug interactions were monitored in patients with severe obesity who underwent bariatric surgery. The drug classes most used were antidepressants, cardiovascular agents, and lipid-modifying agents, with a decrease in use after 12 months of surgery. Before surgery, it was found that more than half of the patients had at least one drug interaction in their therapeutic regimen. Of these, most were classified as moderate. After surgery, a decrease in drug interaction was observed. Serum AAG showed a significant reduction after 12 months, which can influence the free fraction of drugs with a high-affinity rate and how they impact therapeutic efficacy