Patricia Martins Bock

Chronic whole-body heat treatment relieves atherosclerotic lesions, cardiovascular and metabolic abnormalities, and enhances survival time restoring the anti-inflammatory and anti-senescent heat shock response in mice

Unhealthy lifestyle persistently feeds forward inflammation in metabolic organs thus imposing senescence-associated secretory phenotype (SASP), as observed in obesity and type 2 diabetes. However, SASP blocks physiological resolution of inflammation by suppressing the anti-inflammatory and anti-senescent heat shock (HS) response, i.e., the gene program centered in heat shock factor-1 (HSF1)-dependent expression heat shock proteins (HSPs). As SASP-inducing factors are not removed, leading to the perpetuation of inflammation, we argued that SIRT1-HSF1-HSP axis might also be suppressed in atherosclerosis, which could be reversible by heat treatment (HT), the most powerful HS response trigger. LDLr-/- adult mice were fed on high-fat/high-cholesterol diet from the age of 90 days until the end of study (age of 270 days). After 120 days under atherosclerotic diet, the animals were submitted to either whole-body HT (n = 42; 40 °C) or sham (n = 59; 37 °C) treatment (15 min/session), under anesthesia, once a week, for 8 weeks, being echographically and metabolically monitored. Aortic expressions of SIRT1, HSF1, HSP27, HSP72 and HSP73 were progressively depressed in atherosclerotic animals, as compared to normal (LDLr+/+; n = 25) healthy counterparts, which was paralleled by increased expression of NF-κB-dependent VCAM1 adhesion molecule. Conversely, HT completely reversed suppression of the above HS response proteins, while markedly inhibiting both VCAM1 expression and NF-κB DNA-binding activity. Also, HT dramatically reduced plasma levels of TG, total cholesterol, LDL-cholesterol, oxidative stress, fasting glucose and insulin resistance while rising HDL-cholesterol levels. HT also decreased body weight gain, visceral fat, cellular infiltration and aortic fatty streaks, and heart ventricular congestive hypertrophy, thereby improving aortic blood flow and myocardial performance (Tei) indices. Remarkably, heat-treated mice stopped dying after the third HT session (= 8 human years), suggesting a curative effect. Therefore, evolution of atherosclerosis is associated with suppression of the anti-inflammatory and anti-senescent SIRT1-HSF1-HSP molecular axis, which is refreshed by chronic heat treatment.

Heat-induced extracellular HSP72 release is blunted in elderly diabetic people compared with healthy middle-aged and older adults, but it is partially restored by resistance training

Abstract Recent evidence suggests that the anti‐inflammatory heat shock response (HSR) is reduced in aging and diabetes. In this study we compared HSR between healthy middle‐aged adults, healthy elderly and type 2 diabetic (T2DM) elderly, and tested whether resistance training (RT) could improve the HSR in T2DM group. Thirty sedentary participants volunteered for this study. HSR (assessed as the capacity to export HSP72 during heat stress) was measured in the blood and compared between the groups. HSR was similar between healthy middle‐aged and healthy elderly volunteers, but diminished in elderly T2DM (p < 0.001). Hence, T2DM subjects (n = 12) were submitted to a 12‐week RT program, because exercise is a physiological HSR inducer. HSR, cytokines, metabolic parameters and visceral adipose tissue (VAT) were measured before and after the RT. Remarkably, VAT was negatively correlated with HSR (r = − 0.49, p < 0.01) while RT improved the HSR and reduced inflammation [TNF‐&agr;: from 51.5 ± 9 to 40.7 ± 4 pg/mL and TNF‐&agr;/IL‐10 ratio: from 1.55 ± 0.3 to 1.16 ± 0.2 (p < 0.001)], without affecting other parameters. All together, these findings confirm the hypothesis that the anti‐inflammatory HSR is depressed in elderly diabetic people, but can be partially restored by RT. HighlightsHeat Shock Response (HSR) is similar in healthy middle‐aged and elderly people, but is blunted in aged T2DM individuals.Visceral Adipose Tissue (VAT) is increased with age, and the increased VAT is correlated with a lower HSR.Resistance training (RT) is an efficient intervention to restore the HSR and reduce inflammation in aged T2DM individuals.Restoration of HSR may delay the appearance and the establishment of inflammatory‐related diseases.

O papel do fator nuclear eritroide 2 relacionado ao fator 2 (Nrf2) no diabetes mellitus

O diabetes mellitus (DM) e uma doenca metabolica complexa. Sua etiologia e atribuida a uma combinacao entre fatores geneticos, ambientais e de estilo de vida. Contudo, sabe-se que o estresse oxidativo desempenha papel crucial na patogenese do DM, acarretando em disfuncao das celulas β pancreaticas e resistencia a insulina. Neste contexto, o fator nuclear eritroide 2 relacionado ao fator 2 (Nrf2) e considerado o regulador mestre da resposta antioxidante do organismo, sendo um mecanismo de importância critica para a manutencao da homeostase e sobrevivencia celular. Todavia, a funcao do Nrf2 nao se limita somente a resposta antioxidante. Ao interagir com outras vias metabolicas, o Nrf2 possui importante papel na regulacao do metabolismo, atuando no metabolismo dos lipidios, manutencao da glicemia, resposta inflamatoria, entre outros. Entretanto, a exata relacao do Nrf2 com outras vias metabolicas ainda nao e totalmente conhecida. Contudo, sabe-se que o comprometimento da funcao do Nrf2 e evidente na fisiopatologia do DM bem como no desenvolvimento de suas complicacoes clinicas. A ativacao do Nrf2 protege contra os danos mediados pelo DM, podendo ser adequada uma intervencao exogena para aumentar a sua atividade. Palavras-chave: Complicacoes do diabetes; estresse oxidativo; antioxidantes; inflamacao; obesidade

Perfil farmacoterapêutico de pacientes obesos no pós-operatório de cirurgia bariátrica

Resumo Contexto A obesidade pode estar relacionada a doenças como diabetes, hipertensão arterial e dislipidemia. A cirurgia bariátrica é um dos tratamentos mais eficazes, levando à diminuição de peso e comorbidades. Objetivo Avaliar o perfil metabólico e farmacoterapêutico de pacientes obesos após cirurgia bariátrica. Métodos Trata-se de um estudo observacional transversal retrospectivo, realizado em um hospital localizado na cidade de Porto Alegre, RS, Brasil. Foram avaliados 70 prontuários de pacientes que realizaram cirurgia bariátrica, nos períodos de antes de 2 meses e mais de 6 meses após a cirurgia bariátrica. A análise estatística foi realizada no programa SPSS 17.0®. Resultados A pressão arterial inicial foi de 130/85 mmHg, passando para 120/80 mmHg (p < 0,01). Com relação ao perfil metabólico antes de dois meses, o HDL foi de 34 mg/dL, o colesterol total foi de 195,07 ± 40,17 mg/dL, o LDL foi de 118,22 ± 41,28 mg/dL, os triglicerídeos foram de 141,09 ± 43,39 mg/dL, e a glicemia de jejum foi de 90 mg/dL. Após 6 meses de cirurgia, os valores passaram para 43 mg/dL, 133,67 ± 28,14 mg/dL, 65,53 ± 24,3 mg/dL, 104,41 ± 29,6 mg/dL, e 77 mg/dL, respectivamente (p < 0,01). Com relação ao uso de medicamentos, 41% utilizaram anti-hipertensivos, 39% utilizaram hipolipemiantes, 10% utilizaram hipoglicemiantes orais e 97% utilizaram suplementos antes dos 2 meses de cirurgia. Após os 6 meses, os percentuais foram alterados para 21%, 19%, 9% e 99%, respectivamente. Conclusões O estudo mostra o sucesso da cirurgia bariátrica em pacientes obesos com comorbidades, revelando melhora no perfil metabólico e redução na utilização de medicamentos para tratamento de comorbidades.