👤 Kate T Creasy

Short sleep duration, low physical activity (PA), and sedentary behavior (SB) are associated with negative health outcomes and highly prevalent in adolescents. This study examined changes in the amount and timing of PA and SB following a 1-week sleep extension manipulation in adolescents. Forty-three habitually short-sleeping (≤7 h/night on school days), habitually inactive (<3 hours of regular physical activity per week), and healthy-weight adolescents (16.0 ± 1.24 years, 69.8% female; 86% White) completed a randomized crossover procedure during the school year. Participants slept for 1 week on their typical school schedule (Typical Sleep, TS), and 1 week during which time in bed was extended by ≥1 hour each school night (Sleep Extension, EXT). Home-monitoring of sleep with wrist-worn actigraphy and activity with thigh-worn accelerometer was completed during both conditions. Relationships between sleep, SB, PA, and experimental manipulation were assessed with linear mixed models. SB and light PA (LPA) across the 24 days decreased significantly during EXT compared to TS by 72 minutes and 13.2 minutes, respectively (95% CI: -102, -42, p < .001; 95% CI: -26.4, 0.00, p = .048). SB decreased predominantly between the hours of 18:00-00:00 (-39 minute 95% CI: -54.6, -24, p < .001). There was no significant change in moderate-to-vigorous PA (MVPA) between conditions (p > .05). Increased sleep duration replaced time spent in SB primarily in the evening hours. While LPA decreased primarily in the morning hours, the amount of change was small and likely not clinically significant. Sleep extension did not impact MVPA. Show less

Common variants of the max-like protein X (MLX)-interacting protein-like (MLXIPL) gene, encoding the transcription factor carbohydrate-responsive element-binding protein, have been shown to be associated with plasma triglyceride levels. However, the role of these variants in steatotic liver disease (SLD) is unclear. We used a genome-first approach to analyze a variety of metabolic phenotypes and clinical outcomes associated with a common missense variant in MLXIPL, Gln241His, in 2 large biobanks: the UK Biobank and the Penn Medicine Biobank. Carriers of MLXIPL Gln241His were associated with significantly lower serum levels of triglycerides, apolipoprotein-B, gamma-glutamyl transferase, and alkaline phosphatase. Additionally, MLXIPL Gln241His carriers were associated with significantly higher serum levels of HDL cholesterol and alanine aminotransferase. Carriers homozygous for MLXIPL Gln241His showed a higher risk of SLD in 2 unrelated cohorts. Carriers of MLXIPL Gln241His were especially more likely to be diagnosed with SLD if they were female, obese, and/or also carried the PNPLA3 I148M variant. Furthermore, the heterozygous carriage of MLXIPL Gln241His was associated with significantly higher all-cause, liver-related, and cardiovascular mortality rates. Nuclear magnetic resonance metabolomics data indicated that carriage of MLXIPL Gln241His was significantly associated with lower serum levels of VLDL and increased serum levels of HDL cholesterol. Analyses of the MLXIPL Gln241His polymorphism showed a significant association with a higher risk of SLD diagnosis and elevated serum alanine aminotransferase as well as significantly lower serum triglycerides and apolipoprotein-B levels. MLXIPL might, therefore, be a potential pharmacological target for the treatment of SLD and hyperlipidemia, notably for patients at risk. More mechanistic studies are needed to better understand the role of MLXIPL Gln241His on lipid metabolism and steatosis development. Show less