Physical inactivity, i.e., not reaching the recommended level of physical activity (PA) and sedentary behaviors (SB), i.e., sitting time have been associated with increased risk for common metabolic diseases. Recent epidemiological data suggest that high volumes of SB are detrimental for metabolic health, even in the presence of regular exercise, i.e., moderate/vigorous (MVPA). This suggests that the health effects of SB are independent from those of exercise. However, experimentally testing this hypothesis is complicated because of the difficulty in disassociating SB from PA. Bedrest studies, a traditional space science model, can offer new insights. In some bedrest studies, an exercise training protocol has been used to counteract the harmful effects of inactivity. While bedrest induces an inactive and sedentary state, exercise with bedrest represents a unique model of sedentary yet physically active people. Here, we review bedrest studies with and without exercise training.Although exercise training prevents the loss of muscle mass and function, even large volumes of exercise are not sufficient to fully counteract the negative metabolic adaptations triggered by inactivity. This observation supports the existence of independent adverse health effects of SB, but also the potential benefits of non-exercise activity, i.e., daily living light-intensity activities (LPA). We gathered available data to examine the complex relationships between exercise, non-exercise activity, SB and health outcomes. Given the large amount of SB in modern societies, the sole promotion of exercise, i.e., MVPA may be insufficient, and promotion of LPA may be a complimentary approach to improve health.

This study compared 24-h nutrient oxidation responses between a sedentary condition (SED) and a condition in which short 5-min bouts of moderate-intensity physical activity were performed hourly for nine consecutive hours over 4 days (MICRO). To determine whether any shifts in fuel use were due solely to increases in energy expenditure, we also studied a condition consisting of a single isoenergetic 45-min bout of moderate-intensity exercise (ONE). Twenty sedentary overweight or obese adults (10 men/10 women; 32.4 ± 6.3 yr; BMI, 30.6 ± 2.9 kg/m2) completed all three conditions (MICRO, SED, and ONE) in a randomized order. Each condition consisted of a 3-day free-living run-in followed by a 24-h stay in a whole-room calorimeter to measure total energy expenditure (TEE) and substrate utilization. Dietary fat oxidation was also assessed during the chamber stay by administering a [1-13C] oleic acid tracer at breakfast. Energy intake was matched across conditions. Both MICRO and ONE increased TEE relative to SED, resulting in a negative energy balance. HOMA-IR improved in both activity conditions. MICRO increased 24-h carbohydrate oxidation compared with both ONE and SED ( P < 0.01 for both). ONE was associated with higher 24-h total fat oxidation compared with SED, and higher 24-h dietary fat oxidation compared with both SED and MICRO. Differences in substrate oxidation remained significant after adjusting for energy balance. In overweight and obese men and women, breaking up sitting time increased reliance upon carbohydrate as fuel over 24 h, while a single energy-matched continuous bout of exercise preferentially relies upon fat over 24 h. NEW & NOTEWORTHY Insulin sensitivity, as assessed by HOMA-IR, was improved after 4 days of physical activity, independent of frequency and duration of activity bouts. Temporal patterns of activity across the day differentially affect substrate oxidation. Frequent interruptions of sedentary time with short bouts of walking primarily increase 24-h carbohydrate oxidation, whereas an energy-matched single continuous bout of moderate intensity walking primarily increased 24-h fat oxidation.

Office workers are vulnerable to the adverse health effects of sedentary behavior (i.e., sitting time). Increasing physical activity and preventing time spent sitting is an occupational health priority. This randomized crossover design study compared the short-term (3-days) effects of hourly interruptions of sedentary time with 5-min micrrobouts of activity for 9 hours (MICRO) to a sedentary control condition (SED) and a duration-matched continuous single bout of physical activity (45-min/d, ONE) condition on inclinometer-derived sitting-time on work and non-work days in sedentary overweight/obese adults. Differences in sitting/lying, standing, stepping, number of sit/stand transitions, time spent in moderate and vigorous activity (MVPA), energy expenditure, self-perceived vigor and fatigue, and insulin sensitivity were also examined. Twenty-two participants (10M/12F; 31.7 ± 1.3 year old BMI 30.4 ± 0.5 kg/m2) completed all conditions. No between-condition effects were observed in sitting-time and sit/stand transitions. Both interventions increased daily steps, MVPA and energy expenditure with increases being greater in ONE than MICRO. Feelings of vigor and fasting insulin sensitivity were also improved. Participants reported less fatigue with MICRO than SED and ONE. Both interventions increase physical activity and energy expenditure in occupational and leisure-time contexts. The sustainability of these effects over the long term and on health outcomes will need to be tested in future studies.

Breaking up sedentary behavior with short-frequent bouts of physical activity (PA) differentially influences metabolic health compared with the performance of a single-continuous bout of PA matched for total active time. However, the underlying mechanisms are unknown. We compared skeletal muscle mitochondrial respiration (high-resolution respirometry) and molecular adaptations (RNA sequencing) following 4-day exposure to breaks vs. energy-matched single-continuous PA bout in inactive adults with overweight/obesity. Participants (9M/10F, 32.2 ± 6.4 years, 30.3 ± 3.0 kg/m2) completed three 4-day interventions of a randomized cross-over study: SED, sedentary control; MICRO, 5 min brisk walking each hour for 9 h; ONE: 45 min/d continuous brisk walking bout. Fasted muscle biopsies were collected on day 5. Mitochondrial coupling in the presence of lipid-associated substrates was higher after ONE (4.8 ± 2.5) compared to MICRO (3.1 ± 1.1, p = 0.02) and SED (2.3 ± 1.0, p = 0.001). Respiratory rates did not differ across groups with carbohydrate-associated substrates. In pathways associated with muscle contraction transcription signaling, ONE and MICRO similarly enhanced Oxidative Phosphorylation and Sirtuin Signaling expression (p < 0.0001, for both). However, ONE (p < 0.001, for all), but not MICRO, had greater pathway enrichment, including Ca++, mTOR, AMPK, and HIF1α signaling, than SED. Although breaking up sedentary behavior triggered skeletal muscle molecular adaptations favoring oxidative capacity, it did not improve mitochondrial function over the short term.

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