Background:Although the health benefits of regular physical activity and exercise are well established and have been incorporated into national public health recommendations, there is a relative lack of understanding pertaining to the harmful effects of physical inactivity. Experimental paradigms including complete immobilization and bed rest are not physiologically representative of sedentary living. A useful ‘real-world’ approach to contextualize the physiology of societal downward shifts in physical activity patterns is that of short-term daily step reduction.Results:Step-reduction studies have largely focused on musculoskeletal and metabolic health parameters, providing relevant disease models for metabolic syndrome, type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD), sarcopenia and osteopenia/osteoporosis. In untrained individuals, even a short-term reduction in physical activity has a significant impact on skeletal muscle protein and carbohydrate metabolism, causing anabolic resistance and peripheral insulin resistance, respectively. From a metabolic perspective, short-term inactivity-induced peripheral insulin resistance in skeletal muscle and adipose tissue, with consequent liver triglyceride accumulation, leads to hepatic insulin resistance and a characteristic dyslipidaemia. Concomitantly, various inactivity-related factors contribute to a decline in function; a reduction in cardiorespiratory fitness, muscle mass and muscle strength.Conclusions:Physical inactivity maybe particularly deleterious in certain patient populations, such as those at high risk of T2D or in the elderly, considering concomitant sarcopenia or osteoporosis. The effects of short-term physical inactivity (with step reduction) are reversible on resumption of habitual physical activity in younger people, but less so in older adults. Nutritional interventions and resistance training offer potential strategies to prevent these deleterious metabolic and musculoskeletal effects.Impact:Individuals at high risk of/with cardiometabolic disease and older adults may be more prone to these acute periods of inactivity due to acute illness or hospitalization. Understanding the risks is paramount to implementing countermeasures.

Aims/hypothesis Low physical activity levels and sedentary behaviour are associated with obesity, insulin resistance and type 2 diabetes. We investigated the effects of a short-term reduction in physical activity with increased sedentary behaviour on metabolic profiles and body composition, comparing the effects in individuals with first-degree relatives with type 2 diabetes (FDR+ve) vs those without (FDR−ve). Methods Forty-five habitually active participants (16 FDR+ve [10 female, 6 male] and 29 FDR−ve [18 female, 11 male]; age 36 ± 14 years) were assessed at baseline, after 14 days of step reduction and 14 days after resuming normal activity. We determined physical activity (using a SenseWear armband), cardiorespiratory fitness (V : O 2peak ), body composition (dual-energy x-ray absorptiometry/magnetic resonance spectroscopy) and multi-organ insulin sensitivity (OGTT) at each time point. Statistical analysis was performed using a two-factor between-groups ANCOVA, with data presented as mean ± SD or (95% CI). Results There were no significant between-group differences in physical activity either at baseline or following step reduction. During the step-reduction phase, average daily step count decreased by 10,285 steps (95% CI 9389, 11,182; p < 0.001), a reduction of 81 ± 8%, increasing sedentary time by 223 min/day (151, 295; p < 0.001). Pooling data from both groups, following step reduction there was a significant decrease in whole-body insulin sensitivity (Matsuda index) (p < 0.001), muscle insulin sensitivity index (p < 0.001), cardiorespiratory fitness (p = 0.002) and lower limb lean mass (p = 0.004). Further, there was a significant increase in total body fat (p < 0.001), liver fat (p = 0.001) and LDL-cholesterol (p = 0.013), with a borderline significant increase in NEFA AUC during the OGTT (p = 0.050). Four significant between-group differences were apparent: following step reduction, FDR+ve participants accumulated 1.5% more android fat (0.4, 2.6; p = 0.008) and increased triacylglycerol by 0.3 mmol/l (0.1, 0.6; p = 0.044). After resuming normal activity, FDR+ve participants engaged in lower amounts of vigorous activity (p = 0.006) and had lower muscle insulin sensitivity (p = 0.023). All other changes were reversed with no significant between-group differences. Conclusions/interpretation A short-term reduction in physical activity with increased sedentary behaviour leads to a reversible reduction in multi-organ insulin sensitivity and cardiorespiratory fitness, with concomitant increases in central and liver fat and dyslipidaemia. The effects are broadly similar in FDR+ve and FDR−ve individuals. Public health recommendations promoting physical activity should incorporate advice to avoid periods of sedentary behaviour.

Introduction/Purpose To investigate whether (a) lower levels of daily physical activity (PA) and greater sedentary time accounted for contrasting metabolic phenotypes (higher liver fat/presence of metabolic syndrome [METS+] vs lower liver fat/absence of metabolic syndrome [METS−]) in individuals of similar body mass index and (b) the association of sedentary time on metabolic health and liver fat. Methods Ninety-eight habitually active participants (53 female, 45 male; age, 39 ± 13 yr; body mass index 26.9 ± 5.1 kg·m −2 ), underwent assessments of PA (SenseWear armband; wear time ~98%), cardiorespiratory fitness (V˙O 2 peak), body composition (magnetic resonance imaging and magnetic resonance spectroscopy) and multiorgan insulin sensitivity (oral glucose tolerance test). We undertook a) cross-sectional analysis comparing four groups: nonobese or obese, with and without metabolic syndrome (METS+ vs METS−) and b) univariate and multivariate regression for sedentary time and other levels of PA in relation to liver fat. Results Light, moderate, and vigorous PA did not account for differences in metabolic health between individuals, whether nonobese or obese, although METS+ individuals were more sedentary, with a higher number, and prolonged bouts (~1–2 h). Overall, sedentary time, average daily METS and V˙O 2 peak were each independently associated with liver fat percentage. Each additional hour of daily sedentary time was associated with a 1.15% (95% confidence interval, 1.14%–1.50%) higher liver fat content. Conclusions Greater sedentary time, independent of other levels of PA, is associated with being metabolically unhealthy; even in habitually active people, lesser sedentary time, and higher cardiorespiratory fitness and average daily METS is associated with lower liver fat.