Aims/hypothesis We hypothesised that the insulin-sensitising effect of physical activity depends on the timing of the activity. Here, we examined cross-sectional associations of breaks in sedentary time and timing of physical activity with liver fat content and insulin resistance in a Dutch cohort. Methods In 775 participants of the Netherlands Epidemiology of Obesity (NEO) study, we assessed sedentary time, breaks in sedentary time and different intensities of physical activity using activity sensors, and liver fat content by magnetic resonance spectroscopy (n=256). Participants were categorised as being most active in the morning (06:00–12:00 hours), afternoon (12:00–18:00 hours) or evening (18:00–00:00 hours) or as engaging in moderate-to-vigorous-physical activity (MVPA) evenly distributed throughout the day. Most active in a certain time block was defined as spending the majority (%) of total daily MVPA in that block. We examined associations between sedentary time, breaks and timing of MVPA with liver fat content and HOMA-IR using linear regression analyses, adjusted for demographic and lifestyle factors including total body fat. Associations of timing of MVPA were additionally adjusted for total MVPA. Results The participants (42% men) had a mean (SD) age of 56 (4) years and a mean (SD) BMI of 26.2 (4.1) kg/m2. Total sedentary time was not associated with liver fat content or insulin resistance, whereas the amount of breaks in sedentary time was associated with higher liver fat content. Total MVPA (−5%/h [95% CI −10%/h, 0%/h]) and timing of MVPA were associated with reduced insulin resistance but not with liver fat content. Compared with participants who had an even distribution of MVPA throughout the day, insulin resistance was similar (−3% [95% CI −25%, 16%]) in those most active in morning, whereas it was reduced in participants who were most active in the afternoon (−18% [95% CI −33%, −2%]) or evening (−25% [95% CI −49%, −4%]). Conclusions/interpretation The number of daily breaks in sedentary time was not associated with lower liver fat content or reduced insulin resistance. Moderate-to-vigorous activity in the afternoon or evening was associated with a reduction of up to 25% in insulin resistance. Further studies should assess whether timing of physical activity is also important for the occurrence of type 2 diabetes. Graphical abstract

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Purpose-It remains unclear to what extent habitual physical activity and sedentary time are associated with visceral fat and liver fat. We studied substitution of sedentary time with time spent physically active and total body fat (TBF), visceral adipose tissue (VAT) and hepatic triglyceride content (HTGC) in middle-aged men and women. Design-In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, physical activity was assessed in 228 participants using a combined accelerometer and heart rate monitor. Total body fat was assessed by the Tanita bio-electrical impedance, VAT by MRI and HTGC by proton-MR spectroscopy. Behavioural intensity distribution was categorized as sedentary time (ST), time spent in light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). To estimate the effect of replacing 30 minutes/day of ST with 30 minutes/day LPA or MVPA, we performed isotemporal substitution analyses, adjusted for sex, age, ethnicity, education, the Dutch Healthy Diet index, and smoking.Results-Included participants (41% men) had a mean (SD) age of 56 (6) years and spent 88 (56) minutes in MVPA and 9.0 hours (2.1) of ST. Replacing 30 minutes/day of ST with 30 minutes of MVPA was associated with 1.3% less TBF (95% CI: -2.0, -0.7), 7.8 cm 2 less VAT (-11.6, -4.0) and 0.89 times HTGC (0.82, 0.97). Replacement with LPA was not associated with TBF (-0.03 %; -0.5, 0.4), VAT (-1.7 cm 2 ; -4.4, 0.9) or HTGC (0.98 times; 0.92, 1.04).

The antioxidant vitamin E (α-tocopherol, α-TOH) protects lipids from oxidation by reactive oxygen species. We hypothesized that lifestyle factors associate with vitamin E metabolism marked by urinary α-tocopheronolactone hydroquinone (α-TLHQ) and α-carboxymethyl-hydroxychroman (α-CEHC levels), as potential reflection of lipid oxidation. We conducted a cross-sectional study in the Netherlands Epidemiology of Obesity Study. Serum α-TOH, and urinary α-TLHQ and α-CEHC were quantified by liquid chromatography coupled with tandem mass spectrometry. Information on the lifestyle factors (sleep, physical activity (PA), smoking and alcohol) were collected through questionnaires. Multivariable linear regression analyses were performed to assess the associations between the lifestyle factors and α-TOH measures. A total of 530 participants (46% men) were included with mean (SD) age of 56 (6) years. Of the examined lifestyle factors, only poor sleep was associated with a higher serum α-TOH (mean difference: 4% (95% CI: 1, 7%)). Current smoking was associated with higher urinary α-CEHC (32%: (14%, 53%)), with evidence of a dose–response relationship with smoking intensity (low pack years, 24% (2, 52%); high pack years, 55% (25, 93%)). Moderate physical activity was associated with a lower α-TLHQ relative to α-CEHC (−17%: (−26, −6%), compared with low PA). Only specific lifestyle factors associate with vitamin E metabolism. Examining serum α-TOH does not provide complete insight in vitamin E antioxidant capacity.

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