Biology subjects

Domingues, M. R.

Publications and source records attributed to Domingues, M. R..

4 recordsLinked to original sources

bioRxiv2025

Lipid droplet dysmetabolism affects cell homeostasis in an in vitro model of Alzheimer disease

Lipid droplets (LD) are dynamic organelles involved in neutral lipid storage, energy homeostasis, and can prevent lipotoxicity and oxidative distress. LD dysmetabolism has been considered a pathological hallmark in neurodegenerative disorders, including Alzheimers disease (AD). In this study, we investigated the alterations in LD metabolism and their impact on mitochondria-associated membranes (MAM) in an in vitro model of AD, namely the mouse neuroblastoma cell (N2A) line overexpressing the amyloid precursor protein with the familial Swedish mutation (APPswe). In APPswe cells, we found depletion of LD associated with an accumulation of free fatty acids that can be related with the observed LD degradation by chaperone-mediated autophagy. In these cells we also found decreased levels of seipin, which might contribute to triacylglycerol accumulation. These lipid alterations are associated with increased levels of ROS and lipid peroxidation in APPswe cells. The pharmacological modulation of DGAT1, that mediates triacylglycerol synthesis, normalized LD size and improved ER-mitochondria contacts and mitochondrial function in APPswe cells. In summary, these observations suggest the involvement of altered LD metabolism in AD pathophysiology, which impact on MAM and mitochondria function leading to cell dyshomeostasis. Our findings also support the idea that LD are relevant therapeutic targets in AD. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/658644v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@de3fc6org.highwire.dtl.DTLVardef@12d1f2forg.highwire.dtl.DTLVardef@15a5185org.highwire.dtl.DTLVardef@9e1655_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Molecular programming in utero modulates hepatic lipid metabolism and adult metabolic risk in obese mother offspring in a sex-specific manner

Male and female offspring of obese mothers are known to differ significantly in their metabolic adaptation and later development of complications. We investigated the sex-dependent responses in obese offspring of mice with maternal obesity, focusing on changes in liver glucose and lipid metabolism. Maternal obesity prior to and during gestation led to hepatic insulin resistance and inflammation in male offspring, while female offspring were protected. These sex differences were explained by more efficient transcriptional and posttranscriptional reprogramming of metabolic pathways to prevent the damaging effects of maternal obesity in females compared to males. These differences were sustained later in life, resulting in a better metabolic balance in female offspring. In conclusion, sex and maternal obesity drive transcriptional and posttranscriptional regulation of major metabolic processes in offspring liver differently, explaining the sexual dimorphism in obesity-associated metabolic risk.

physiology↗

bioRxiv2021

Maternal obesity programs white and brown adipose tissue transcriptome and lipidome in offspring in a sex-dependent manner

The prevalence of overweight and obesity among children has drastically increased during the last decades and maternal obesity has been demonstrated as one of the ultimate factors. Nutrition-stimulated transgenerational epigenetic regulation of key metabolic genes is fundamental to the developmental origins of the metabolic syndrome. Fetal nutrition may differently influence female and male offspring. In this work, we investigated the sex-dependent programming of maternal obesity in visceral, subcutaneous and brown adipose tissues of offspring using magnetic resonance imaging and spectroscopy and a lipidomic approach combined with a Smart-Seq2 differential sequencing analysis. We show that the triglyceride profile varies between adipose depots, sexes and maternal diet. Our results demonstrate for the first time that a sex-dependent gene programming exists in visceral, subcutaneous and brown adipose tissues. Maternal obesity differentially programs gene expression in adipose depots of female and male offspring, which may contribute to the sex-dependent metabolic complications later in life. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=146 SRC="FIGDIR/small/430188v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@8ceac8org.highwire.dtl.DTLVardef@18a2a32org.highwire.dtl.DTLVardef@1d8530dorg.highwire.dtl.DTLVardef@1349512_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2019

How many days are needed to estimate accelerometry-assessed physical activity during pregnancy? Methodological analyses based on a cohort study using wrist-worn accelerometer

BackgroundObjective methods to measure physical activity (PA) can lead to better cross-cultural comparisons, monitoring temporal PA trends, and measuring the effect of interventions. However, when applying this technology in field-work, the accelerometer data processing is prone to methodological issues. One of the most challenging issues relates to standardizing total wear time to provide reliable data across participants. It is generally accepted that at least 4 complete days of accelerometer wear represent a week for adults. It is not known if this same assumption holds true for pregnant women.\n\nAimWe assessed the optimal number of days needed to obtain reliable estimates of overall PA and moderate-to-vigorous physical activity (MVPA) during pregnancy using a raw triaxial wrist-worn accelerometer.\n\nMethodsCross-sectional analyses were carried out in the antenatal wave of the 2015 Pelotas (Brazil) Birth Cohort Study. Participants wore the wrist ActiGraph wGT3X-BT accelerometer for seven consecutive days. The daily average acceleration, which indicates overall PA, was measured as milli-g (mg), and time spent in MVPA (minutes/day) was analyzed in 5-minute bouts. ANOVA and Kruskal-Wallis tests were used to compare variability across days of the week. Bland-Altman plots and Spearman-Brown Prophecy Formula were applied to determine the reliability coefficient associated with one to seven days of measurement. Analyses were stratified by sociodemographic factors and nutritional status.\n\nResultsAmong 2,082 pregnant women who wore the accelerometer for seven complete days, overall and MVPA were lower on Sundays compared to other days of the week. Reliability of >=0.80 to evaluate overall PA was reached with at least three monitoring days, whereas six days were needed to estimate reliable measures of MVPA.\n\nConclusionsOur findings indicate that the usual approach obtaining one week of accelerometry in adults is also appropriate for pregnant women, particularly to obtain differences on weekend days and reliably estimate MVPA.

epidemiology↗