Even when adults meet physical activity guidelines, sitting for prolonged periods can compromise metabolic health Television (TV) time and objective measurement studies show deleterious associations, and breaking up sedentary time is beneficial Sitting time, TV time, and time sitting in automobiles increase premature mortality risk Further evidence from prospective studies, intervention trials, and population-based behavioral studies is required

Too Much Sitting: The Population Health Science of Sedentary Behavior

It is not uncommon for people to spend one-half of their waking day sitting, with relatively idle muscles. The other half of the day includes the often large volume of nonexercise physical activity. Given the increasing pace of technological change in domestic, community, and workplace environments, modern humans may still not have reached the historical pinnacle of physical inactivity, even in cohorts where people already do not perform exercise. Our purpose here is to examine the role of sedentary behaviors, especially sitting, on mortality, cardiovascular disease, type 2 diabetes, metabolic syndrome risk factors, and obesity. Recent observational epidemiological studies strongly suggest that daily sitting time or low nonexercise activity levels may have a significant direct relationship with each of these medical concerns. There is now a need for studies to differentiate between the potentially unique molecular, physiologic, and clinical effects of too much sitting (inactivity physiology) separate from the responses caused by structured exercise (exercise physiology). In theory, this may be in part because nonexercise activity thermogenesis is generally a much greater component of total energy expenditure than exercise or because any type of brief, yet frequent, muscular contraction throughout the day may be necessary to short-circuit unhealthy molecular signals causing metabolic diseases. One of the first series of controlled laboratory studies providing translational evidence for a molecular reason to maintain high levels of daily low-intensity and intermittent activity came from examinations of the cellular regulation of skeletal muscle lipoprotein lipase (LPL) (a protein important for controlling plasma triglyceride catabolism, HDL cholesterol, and other metabolic risk factors). Experimentally reducing normal spontaneous standing and ambulatory time had a much greater effect on LPL regulation than adding vigorous exercise training on top of the normal level of nonexercise activity. Those studies also found that inactivity initiated unique cellular processes that were qualitatively different from the exercise responses. In summary, there is an emergence of inactivity physiology studies. These are beginning to raise a new concern with potentially major clinical and public health significance: the average nonexercising person may become even more metabolically unfit in the coming years if they sit too much, thereby limiting the normally high volume of intermittent nonexercise physical activity in everyday life. Thus, if the inactivity physiology paradigm is proven to be true, the dire concern for the future may rest with growing numbers of people unaware of the potential insidious dangers of sitting too much and who are not taking advantage of the benefits of maintaining nonexercise activity throughout much of the day.

https://diabetes.diabetesjournals.org/content/diabetes/56/11/2655.full.pdf

Role of Low Energy Expenditure and Sitting in Obesity, Metabolic Syndrome, Type 2 Diabetes, and Cardiovascular Disease

KATZMARZYK, P. T., T. S. CHURCH, C. L. CRAIG, and C. BOUCHARD. Sitting Time and Mortality from All Causes, Cardiovascular Disease, and Cancer. Med. Sci. Sports Exerc., Vol. 41, No. 5, pp. 998–1005, 2009. Purpose: Although moderate-tovigorous physical activity is related to premature mortality, the relationship between sedentary behaviors and mortality has not been fully explored and may represent a different paradigm than that associated with lack of exercise. We prospectively examined sitting time and mortality in a representative sample of 17,013 Canadians 18–90 yr of age. Methods: Evaluation of daily sitting time (almost none of the time, one fourth of the time, half of the time, three fourths of the time, almost all of the time), leisure time physical activity, smoking status, and alcohol consumption was conducted at baseline. Participants were followed prospectively for an average of 12.0 yr for the ascertainment of mortality status. Results: There were 1832 deaths (759 of cardiovascular disease (CVD) and 547 of cancer) during 204,732 person-yr of follow-up. After adjustment for potential confounders, there was a progressively higher risk of mortality across higher levels of sitting time from all causes (hazard ratios (HR): 1.00, 1.00, 1.11, 1.36, 1.54; P for trend G0.0001) and CVD (HR: 1.00, 1.01, 1.22, 1.47, 1.54; P for trend G0.0001) but not cancer. Similar results were obtained when stratified by sex, age, smoking status, and body mass index. Age-adjusted all-cause mortality rates per 10,000 person-yr of follow-up were 87, 86, 105, 130, and 161 (P for trend G0.0001) in physically inactive participants and 75, 69, 76, 98, 105 (P for trend = 0.008) in active participants across sitting time categories. Conclusions: These data demonstrate a dose–response association between sitting time and mortality from all causes and CVD, independent of leisure time physical activity. In addition to the promotion of moderate-to-vigorous physical

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Sitting time and mortality from all causes, cardiovascular disease, and cancer.

Aims/hypothesis
Sedentary (sitting) behaviours are ubiquitous in modern society. We conducted a systematic review and meta-analysis to examine the association of sedentary time with diabetes, cardiovascular disease and cardiovascular and all-cause mortality.

/pdf/sedentary-time-in-adults-and-the-association-with-diabetes-1qtz2honr6.pdf

Sedentary time in adults and the association with diabetes, cardiovascular disease and death: systematic review and meta-analysis

OBJECTIVE —Total sedentary (absence of whole-body movement) time is associated with obesity, abnormal glucose metabolism, and the metabolic syndrome. In addition to the effects of total sedentary time, the manner in which it is accumulated may also be important. We examined the association of breaks in objectively measured sedentary time with biological markers of metabolic risk.

RESEARCH DESIGN AND METHODS —Participants ( n = 168, mean age 53.4 years) for this cross-sectional study were recruited from the 2004–2005 Australian Diabetes, Obesity and Lifestyle study. Sedentary time was measured by an accelerometer (counts/minute−1 < 100) worn during waking hours for seven consecutive days. Each interruption in sedentary time (counts/min ≥100) was considered a break. Fasting plasma glucose, 2-h plasma glucose, serum triglycerides, HDL cholesterol, weight, height, waist circumference, and resting blood pressure were measured. MatLab was used to derive the breaks variable; SPSS was used for the statistical analysis.

RESULTS —Independent of total sedentary time and moderate-to-vigorous intensity activity time, increased breaks in sedentary time were beneficially associated with waist circumference (standardized β = −0.16, 95% CI −0.31 to −0.02, P = 0.026), BMI (β = −0.19, −0.35 to −0.02, P = 0.026), triglycerides (β = −0.18, −0.34 to −0.02, P = 0.029), and 2-h plasma glucose (β = −0.18, −0.34 to −0.02, P = 0.025).

CONCLUSIONS —This study provides evidence of the importance of avoiding prolonged uninterrupted periods of sedentary (primarily sitting) time. These findings suggest new public health recommendations regarding breaking up sedentary time that are complementary to those for physical activity.

https://care.diabetesjournals.org/content/diacare/31/4/661.full.pdf

Breaks in Sedentary Time: Beneficial associations with metabolic risk

We have examined the regulation of lipoprotein lipase (LPL) activity in skeletal muscle during physical inactivity in comparison to low-intensity contractile activity of ambulatory controls. From studies acutely preventing ambulatory activity of one or both the hindlimbs in rats, it was shown that ≈90–95 % of the heparin-releasable (HR) LPL activity normally present in rat muscle with ambulatory activity is lost, and thus dependent on local contractile activity. Similarly, ≈95 % of the differences in LPL activity between muscles of different fibre types was dependent on ambulatory activity. The robustness of the finding that physical inactivity significantly decreases muscle LPL activity was evident from confirmatory studies with different models of inactivity, in many rats and mice, both sexes, three muscle types and during both acute and chronic (11 days) treatment. Inactivity caused a local reduction of plasma [3H]triglyceride uptake into muscle and a decrease in high density lipoprotein cholesterol concentration. LPL mRNA was not differentially expressed between ambulatory controls and either the acutely or chronically inactive groups. Instead, the process involved a rapid loss of the HR-LPL protein mass (the portion of LPL largely associated with the vascular endothelium) by an actinomycin D-sensitive signalling mechanism (i.e. transcriptionally dependent process). Significant decreases of intracellular LPL protein content lagged behind the loss of HR-LPL protein. Treadmill walking raised LPL activity ≈8-fold (P < 0.01) within 4 h after inactivity. The striking sensitivity of muscle LPL to inactivity and low-intensity contractile activity may provide one piece of the puzzle for why inactivity is a risk factor for metabolic diseases and why even non-vigorous activity provides marked protection against disorders involving poor lipid metabolism.

Suppression of skeletal muscle lipoprotein lipase activity during physical inactivity: a molecular reason to maintain daily low-intensity activity

Physical inactivity and unloading lead to diverse skeletal muscle alterations. Our goal was to identify the genes in skeletal muscle whose expression is most sensitive to periods of unloading/reduced physical activity and that may be involved in triggering initial responses before phenotypic changes are evident. The ability of short periods of physical activity/loading as an effective countermeasure against changes in gene expression mediated by inactivity was also tested. Affymetrix microarrays were used to compare mRNA levels in the soleus muscle under three experimental treatments (n = 20-29 rats each): 12-h hindlimb unloading (HU), 12-h HU followed by 4 h of intermittent low-intensity ambulatory and postural activity (4-h reloading), and control (with ambulatory and postural activity). Using a combination of criteria, we identified a small set of genes (approximately 1% of 8,738 genes on the array or 4% of significant expressed genes) with the most reproducible and largest responses to altered activity. Analysis revealed a coordinated regulation of transcription for a large number of key signaling proteins and transcription factors involved in protein synthesis/degradation and energy metabolism. Most (21 of 25) of the gene expression changes that were downregulated during HU returned at least to control levels during the reloading. In surprising contrast, 27 of 38 of the genes upregulated during HU remained significantly above control, but most showed trends toward reversal. This introduces a new concept that, in general, genes that are upregulated during unloading/inactivity will be more resistant to periodic reloading than those genes that are downregulated. This study reveals genes that are the most sensitive to loading/activity in rat skeletal muscle and indicates new targets that may initiate muscle alterations during inactivity.

Patterns of global gene expression in rat skeletal muscle during unloading and low-intensity ambulatory activity

Physical activity often declines with age because of a reduction in the spontaneous activities of daily living and because of less intense exercise. In controlled studies of young rats, it was shown that physical activities associated with walking and standing were especially important for maintaining a high level of lipoprotein lipase (LPL) activity in postural skeletal muscles (slow-twitch oxidative muscles). More intense contractions during run training were important for a high LPL activity in the fast-twitch glycolytic muscles. Aging also causes a fiber type-specific decrease of skeletal muscle LPL activity and LPL protein in weight-bearing skeletal muscles (and no aging effect in glycolytic muscles). Thus, contractile inactivity may be a significant factor causing sub-optimal triglyceride metabolism in skeletal muscles during both unloading in young animals and aging. Measurements of plasma LPL activity, plasma triglyceride (TG) clearance rates, postprandial hypertriglyceridemia after oral fat tolerance tests, and fasting TG levels were generally indicative of reduced plasma TG metabolism during middle or old age. In contrast, older endurance-trained individuals had a favorable blood lipid profile compared to age-matched or young controls, even when the controls were not overweight. Therefore, the poor TG metabolism that is frequently associated with aging may be caused by some of the same processes that lower skeletal muscle LPL activity of young sedentary individuals.

Plasma triglyceride metabolism in humans and rats during aging and physical inactivity.

Lipoprotein lipase (LPL) is a key enzyme for fatty acid and lipoprotein metabolism in muscle. However, the effect of aging on LPL regulation in skeletal muscle is unknown. We report the effect of a...

Reduced lipoprotein lipase activity in postural skeletal muscle during aging

Cloning, sequencing and structural analysis of 976 base pairs of the promoter sequence for the rat lipoprotein lipase gene. Comparison with the mouse and human sequences.

Lionel Bey

Papers

Suppression of skeletal muscle lipoprotein lipase activity during physical inactivity: a molecular reason to maintain daily low-intensity activity

Patterns of global gene expression in rat skeletal muscle during unloading and low-intensity ambulatory activity

Plasma triglyceride metabolism in humans and rats during aging and physical inactivity.

Reduced lipoprotein lipase activity in postural skeletal muscle during aging

Cloning, sequencing and structural analysis of 976 base pairs of the promoter sequence for the rat lipoprotein lipase gene. Comparison with the mouse and human sequences.