Investigação de parâmetros circadianos associados a alterações metabólicas e obesidade

Relevância: Oscilações comportamentais e fisiológicas diárias são uma característica fundamental da biologia de mamíferos. Para permitir que estes ritmos estejam sincronizados com o ambiente externo, mamíferos desenvolveram um relógio circadiano endógeno que responde a pistas ambientais, como o ciclo claro-escuro e os horários de alimentação. No entanto, com a adoção de um estilo de vida moderno, caracterizado por exposição à luz inadequada, jetlag social, hábitos alimentares irregulares, sedentarismo e estresse, a organização dos ritmos circadianos tem sido ameaçada. Estas mudanças ambientais contribuem para o desenvolvimento de diversas patologias, incluindo depressão, obesidade, doenças cardiovasculares e câncer. Objetivos: avaliar a influência de diferentes padrões de iluminação sobre a fisiologia e metabolismo de ratas Wistar. Além disso, identificar associações entre padrões de ritmos de atividade-repouso, exposição à luz e urbanização com índice de massa corporal em comunidades rurais e urbanas. Métodos: Estudo 1: ratas Wistar foram alocadas desde a gestação em quatro padrões de iluminação: combinação de cores RGB (vermelho, red; verde, green; azul, blue) que variam sua composição espectral ao longo do dia (RGB-v; N = 14), RGB durante o fotoperíodo com uma temperatura de cor fixa (RGB-f; N = 13), escuro constante (DD; N = 13) e claro constante (LL; N = 15). Os experimentos foram realizados em fêmeas desde o dia pós-natal (PND) 22 ao 50. Peso corporal, abertura vaginal, ciclicidade estral e parâmetros metabólicos séricos foram mensurados. Estudo 2: Foram coletados dados antropométricos de moradores de comunidades quilombolas rurais e urbanas para calcular o índice de massa corporal, que foi categorizado em: ≥18.5 kg/m² to <25 kg/m² = peso normal; ≥25 kg/m² to <30 kg/m² = sobrepeso; ≥30 kg/m² = obesidade. Os participantes também foram questionados a respeito das suas rotinas de sono e exposição à luz utilizando o Questionário de Cronotipos de Munique (n = 244). Por fim, foram analisados dados de actimetria de 121 participantes com 7 dias de registros consecutivos. Resultados: Estudo 1: o grupo RGB-f apresentou o primeiro ciclo estral completo mais cedo quando comparado ao grupo RGB-v. Fêmeas expostas ao claro constante apresentaram peso corporal mais baixo do PND 33 ao 47 quando comparadas ao restante dos grupos. Foram observados níveis plasmáticos de triglicerídeos maiores no grupo exposto ao escuro constante, quando comparado aos grupos RGB-v e RGB-f. O colesterol total foi mais baixo no grupo RGB-v em relação aos outros grupos. Por fim, a gordura visceral foi maior no grupo RGB-f quando comparado ao grupo LL. Estudo 2: Viver em áreas mais urbanizadas e ter maior variabilidade nos ritmos de atividade-repouso foram associados a maior risco para sobrepeso/obesidade, controlando para sexo e idade. Conclusões: Este trabalho contribui para o conhecimento sobre o papel da exposição à luz e das características dos ritmos circadianos sobre o desenvolvimento de alterações metabólicas e obesidade. Além disso, estes resultados apontam para novas estratégias na prevenção da obesidade e promoção de perfis metabólicos saudáveis.Relevance: Daily behavioral and physiological fluctuations are a fundamental feature of the mammalian biology. For synchronizing these rhythms with the external environment, mammals have developed an endogenous circadian clock that responds to environmental cues such as the light-dark cycle and feeding schedules. However, with the adoption of modern lifestyles, characterized by inadequate light exposure, social jetlag, irregular eating habits, sedentary lifestyle and stress, the organization of circadian rhythms has been threatened. These environmental changes contribute to the development of several pathologies, including depression, obesity, cardiovascular disease and cancer. Objectives: to evaluate the influence of different lighting patterns on the physiology and metabolism of Wistar rats. Furthermore, to identify associations between patterns of activity-rest rhythms, light exposure and urbanization with body mass index in rural and urban communities. Methods: Study 1: Female Wistar rats were allocated from gestation into four lighting patterns: RGB color combination (red, red; green, green; blue, blue) varying their spectral composition throughout the day (RGB-v; N = 14), RGB during the photoperiod with a fixed color temperature (RGB-f; N = 13), constant dark (DD; N = 13) and constant light (LL; N = 15). The experiments were performed on females from postnatal day (PND) 22 to 50. Body weight, vaginal opening, estrous cyclicity and serum metabolic parameters were measured. Study 2: Anthropometric data were collected from residents of rural and urban quilombolas communities to calculate the body mass index, which was then categorized into: ≥18.5 kg/m² to <25 kg/m² = normal weight; ≥25 kg/m² to <30 kg/m² = overweight; ≥30 kg/m² = obesity. Participants were also asked about their sleep routines and light exposure using the Munich Chronotype Questionnaire (n = 244). Finally, actimetry data from 121 participants with 7 days of consecutive records were analyzed. Results: Study 1: the RGB-f group presented the first complete estrous cycle earlier when compared to the RGB-v group. Females exposed to constant light had lower body weight from PND 33 to 47 when compared to the rest of the groups. Higher plasma triglyceride levels were observed in the group exposed to constant dark, when compared to the RGB-v and RGB-f groups. Total cholesterol was lower in the RGB-v group than in the other groups. Finally, visceral fat was higher in the RGB-f group when compared to the LL group. Study 2: Living in more urbanized areas and having higher variability in activity-rest rhythms were associated with a higher risk of overweight/obesity, controlling for sex and age. Conclusions: This work contributes to the knowledge about the role of light exposure and the circadian rhythms features on the development of metabolic alterations and obesity. Furthermore, these results point to new strategies aiming to prevent obesity and promote healthy metabolic profiles

Avaliação do efeito de diferentes padrões de iluminação no desenvolvimento puberal de ratas Wistar

A puberdade é uma fase associada a diversas mudanças físicas e comportamentais, as quais são estabelecidas pela ativação do eixo hipotálamo-hipófise-gônadas (HPG). O sistema circadiano é um programa temporal que atribui e organiza ritmos biológicos, além de permitir que eles estejam sincronizados com o ambiente. O ciclo reprodutivo feminino é regulado pelo sistema circadiano, que é sensível a diversos estímulos externos, principalmente o ciclo claro-escuro. Disrupções no sistema circadiano, causadas pela crescente exposição à iluminação artificial, podem causar alterações nos ritmos biológicos, anormalidades nos ciclos reprodutivos e mudanças em parâmetros metabólicos. No presente trabalho, foi avaliado o efeito de quatro diferentes padrões de iluminação no desenvolvimento puberal de ratas Wistar. Além disso, foram analisadas possíveis alterações metabólicas influenciadas por estes regimes de iluminação. A obtenção das fêmeas passou por um processo inicial de acasalamentos dentro de uma estante de fotoperíodos, para que as fêmeas fossem expostas desde a gestação aos padrões de iluminação. Assim, foram divididas em quatro grupos: combinação de cores RGB (vermelho, red; verde, green; azul, blue) que variam sua composição espectral ao longo do dia (RGB-v; N = 14), RGB durante o fotoperíodo com uma temperatura de cor fixa (RGB-f; N = 13), escuro constante (DD; N = 13) e claro constante (LL; N = 15). Os experimentos foram realizados em fêmeas desde o dia pós-natal (PND) 22 ao 50. Peso corporal, abertura vaginal, ciclicidade estral e parâmetros metabólicos séricos foram mensurados. Não foram observadas diferenças significativas na idade de abertura vaginal, no entanto, o grupo RGB-f apresentou o primeiro ciclo estral completo significativamente mais cedo quando comparado ao grupo RGB-v. Fêmeas expostas ao claro constante apresentaram peso corporal significativamente mais baixo do PND 33 ao 47 quando comparadas ao restante dos grupos. Em relação aos parâmetros metabólicos, foram observados níveis plasmáticos de triglicerídeos significativamente maiores no grupo exposto ao escuro constante, quando comparado aos grupos RGB-v e RGB-f. O colesterol total foi significativamente mais baixo no grupo RGB-v em relação aos outros grupos. Por fim, a gordura visceral foi significativamente maior no grupo RGB-f quando comparado ao grupo LL. Considerando os dados apresentados, é possível sugerir que tanto mudanças no fotoperíodo quanto na qualidade de iluminação afetam o desenvolvimento puberal e alteram o perfil lipídico e acúmulo de gordura visceral de ratas Wistar.Puberty is associated with several physical and behavioral changes, which are shaped by the activation of the hypothalamic-pituitary-gonadal (HPG) axis. The circadian system is a temporal program that assigns and organizes biological rhythms, in addition to allowing them to be synchronized with the environment. The female reproductive cycle is regulated by the circadian system, which is sensitive to several external stimuli, especially the light-dark cycle. Disruptions in the circadian system, caused by increased exposure to artificial lighting, can cause changes in biological rhythms, abnormalities in reproductive cycles and changes in metabolic parameters. In the present study, we evaluated the effect of four different lighting patterns on pubertal development of Wistar rats. In addition, possible metabolic changes influenced by these lighting regimes were analyzed. Females were obtained from a process of mating within a photoperiod station, so that females were exposed to different lighting patterns since gestation. Thus, they were divided into four groups: RGB color combination (red, red, green, blue, blue) varying their spectral composition throughout the day (RGB-v; N = 14), RGB during the photoperiod with a fixed light color temperature (RGB-f; N = 13) during the whole photoperiod, constant dark (DD; N = 13) and constant clear (LL; N = 15). The experiments were performed in females from the postnatal day (PND) 22 to 50. Body weight, vaginal opening, estrous cyclicity and serum metabolic parameters were measured. No significant differences were observed in the age of vaginal openning, however, the RGB-f group exhibited the first complete estrous cycle significantly earlier when compared to the RGB-v group. Females exposed to constant light showed significantly lower body weight from PND 33 to 47 when compared to the rest of the groups. Regarding metabolic parameters, significantly higher triglyceride plasma levels were observed in the group exposed to constant dark when compared to the RGB-v and RGB-f groups. Total cholesterol was significantly lower in the RGB-v group than in the other groups. Finally, visceral fat was significantly higher in the RGB-f group when compared to the LL group. Considering the data presented, it is possible to suggest that both changes in photoperiod and lighting quality affect pubertal development and alter the lipid profile and accumulation of visceral fat of Wistar rats

Relationship between circadian strain, light exposure, and body mass index in rural and urban quilombola communities

Industrialization has greatly changed human lifestyle; work and leisure activities have been moved indoors, and artificial light has been used to illuminate the night. As cyclic environmental cues such as light and feeding become weak and/or irregular, endogenous circadian systems are increasingly being disrupted. These disruptions are associated with metabolic dysfunction, possibly contributing to increased rates of overweight and obesity worldwide. Here, we aimed to investigate how activity-rest rhythms, patterns of light exposure, and levels of urbanization may be associated with body mass index (BMI) in a sample of rural and urban Quilombola communities in southern Brazil. These are characterized as remaining social groups who resisted the slavery regime that prevailed in Brazil. Quilombola communities were classified into five groups according to their stage of urbanization: from rural areas with no access to electricity to highly urbanized communities. We collected anthropometric data to calculate BMI, which was categorized as follows: from ≥ 18.5 kg/m2 to < 25 kg/m2 = normal weight; from ≥ 25 kg/m2 to < 30 kg/m2 = overweight; and ≥ 30 kg/m2 = obese. Subjects were asked about their sleep routines and light exposure on workdays and work-free days using the Munich Chronotype Questionnaire (N = 244 included). In addition, we analyzed actimetry data from 121 participants with seven consecutive days of recordings. Living in more urbanized areas and higher intradaily variability (IV) of activity-rest rhythms were associated with an increased risk of belonging to the overweight or obese group, when controlling for age and sex. These findings are consistent with preclinical data and point to potential strategies in obesity prevention and promotion of healthy metabolic profiles

Circadian strain, light exposure, and depressive symptoms in rural communities of Southern Brazil

Irregular light–dark cycles and circadian/sleep disturbances have been suggested as risk or co-occurring factors in depression. Among a set of metrics developed to quantify strain on the circadian system, social jetlag (SJL) has been put forward as a measure of the discrepancy between biological and social clocks. Here, we approached the question on whether light exposure and SJL would also be associated with depressive symptoms in Quilombola communities in Southern Brazil. These rural communities are void of potential confounders of modern lifestyles and show low levels of SJL. 210 Quilombolas (age range 16–92; 56% women) were asked about their sleep times and light exposure using the Munich ChronoType Questionnaire (MCTQ). The Beck Depression Inventory (BDI) was used to assess depressive symptoms. Additionally, we analyzed 7-day actimetry recordings in 124 subjects. BDI scores higher than 10 (having clinically significant depressive symptoms; controlled for age and sex in the multivariate analysis) were positively associated with SJL >1 h and negatively associated with median light exposure during the day, especially in the morning from 8:00 to 10:00. Our results suggest that low light exposure during the day, and higher levels of SJL are associated with depressive symptoms; longitudinal and experimental studies are needed to understand the underlying mechanisms. Nevertheless, we highlight the potential of treatment strategies aimed at decreasing circadian strain and insufficient light exposure, which are suggested as areas of further research in Psychiatry

Effective recommendations towards healthy routines to preserve mental health during the COVID-19 pandemic

Objective: To assess the adherence to a set of evidence-based recommendations to support mental health during the coronavirus disease 2019 (COVID-19) pandemic and its association with depressive and anxiety symptoms. Methods: A team of health workers and researchers prepared the recommendations, formatted into three volumes (1: COVID-19 prevention; 2: Healthy habits; 3: Biological clock and sleep). Participants were randomized to receive only Volume 1 (control), Volumes 1 and 2, Volumes 1 and 3, or all volumes. We used a convenience sample of Portuguese-speaking participants over age 18 years. An online survey consisting of sociodemographic and behavioral questionnaires and mental health instruments (Patient Health Questionnaire-9 [PHQ-9] and Generalized Anxiety Disorder-7 [GAD-7]) was administered. At 14 and 28 days later, participants were invited to complete follow-up surveys, which also included questions regarding adherence to the recommendations. A total of 409 participants completed the study – mostly young adult women holding university degrees. Results: The set of recommendations contained in Volumes 2 and 3 was effective in protecting mental health, as suggested by significant associations of adherence with PHQ-9 and GAD-7 scores (reflecting anxiety and depression symptoms, respectively). Conclusion: The recommendations developed in this study could be useful to prevent negative mental health effects in the context of the pandemic and beyond