Levine, James A.

Introduction: Identifying and mitigating factors that promote obesity will have a large public health impact. Sleep may be an important regulator of metabolism and energy expenditure. Voluntary sleep restriction is common, with 27% of US adults regularly getting ≤6 h of sleep per day. Epidemiologic evidence suggests a link between short sleep duration and obesity. Human experiments suggest that acute sleep deprivation reduces the anorexigenic hormone leptin, increases the orexigenic factor ghrelin, and promotes caloric intake. Meanwhile, increased energy expenditure during prolonged wakefulness may counterbalance any increased caloric intake associated with a lack of sleep. Hypothesis: We hypothesized that 8 days of modest sleep restriction would reduce leptin, increase ghrelin, promote caloric intake, and increase activity energy expenditure. Methods: We studied 17 healthy individuals age 18–40 y. Subjects completed a protocol consisting of one week of home actigraphy, a 3 night acclimation phase, followed by an 8 night experimental phase in which they were randomized to sleep ad lib or two-thirds of their normal sleep time. Blood was collected at the end of the two periods, food was freely available and caloric intake was calculated daily, and activity energy expenditure was assessed by a comprehensively validated system comprised of inclinometers and accelerometers. Sleep was confirmed using continuous electroencephalography. Mean change from the acclimation period ± standard deviation are presented, with statistical testing by two sample t tests on the changes between acclimation and experimental periods. Results: Subjects included 11 men and 6 women, of whom 8 were randomized to sleep deprivation and 9 served as controls. Sleep duration during the acclimation period averaged 6.5±0.9 h/day but fell to 5.2±0.1 h/d among those randomized to sleep deprivation. The sleep deprivation group consumed +549±583 kcal/d, whereas those randomized to ad lib sleep consumed −143±420 kcal/d (P<0.01). Activity energy expenditure by did not change in either group (+1.2±33.0% vs +8.4±34.0%, P=0.68). Sleep deprivation was associated with a trend towards increased leptin (+8.4±4.7% versus −9.8±13.5%, P=0.12) and decreased ghrelin (−4.9±5.3% vs +4.6±7.0%, P=0.38). Conclusions: Eight days of modest sleep restriction, similar to that encountered in everyday life, was associated with a striking increase in caloric intake with no change in activity energy expenditure. Contrary to expectations, we observed a trend towards increased circulating concentrations of leptin and reduced concentrations of ghrelin, more consistent with a consequence of a positive energy balance than a cause. Our data suggest that chronic sleep restriction may be an important and modifiable behavior promoting obesity.

Triiodothyronine (T3) has a major impact on the regulation of energetics and mitochondrial (mt) function. We determined whether chronic T3 administration alters the age‐related decline in mt function. Ten young (Y, 8 mo) and ten old (O, 27 mo) F344/BN rats were randomized to receive T3 (200 mg/d) or placebo for 14d via subcutaneous osmotic pump. Because OT3 rats decreased food consumption by 39%, we added ten pair fed rats (OPF). T3 treatment caused a significant weight loss (Y, −11.97%; O, −17.49%), while energy expenditure increased in both Y (50.86%) and O (54.40%), but decreased in PF (17.55%). Fat and muscle loss were similar in Y and O in response to T3 (fat, −52.53%(Y) vs −51.69% (O); muscle, −21.50% (Y) vs −21.03% (O) in soleus and −16.70% (Y) vs −17.35% (O) in plantaris), whereas these changes were minor with OPF (fat, −10.4%; soleus −1.69% ; plantaris 7.69%). While mt ATP production and citrate synthase activity in heart and soleus muscle were lower in O, these measures increased equally in Y and O in response to T3. In the soleus, mt DNA abundance increased in Y (54.39%) and O (23.36%) and UCP3 expression increased 10‐fold in both age groups. Gene transcripts levels of PGC1α, COX3&4 and NADH4, UCP2& 3 increased in soleus of T3 rats. In conclusion, T3 similarly increased energy expenditure, weight loss and mt biogenesis in both Y and O rats, despite differences in food intake. NIH grant PO1 AG09531 and Mayo Foundation

Aging is associated with a concomitant decline in non exercise activity (NEA) and mitochondrial ATP production rate (MAPR) in skeletal muscle. To determine whether caloric restriction (CR) could prevent the decline in MAPR and NEA we studied young (Y, 7 month‐old, n=8), old (O, 27 month‐old, n=7) and old caloric‐restricted F344/BN rats (OCR, 27 month‐old, 40% CR from 16 weeks of age, n=7). Energy expenditure (kcal/d/gBW) was lower in O (0.311±0.005) than Y (0.365±0.004) and was higher in OCR (0.341±0.008) (P<0.05). Muscle mass (mg/gBW) of O was lower than Y, and Y and OCR are similar (Y=0.96±0.18, O=0.71±0.16, OCR=1.03±0.04; P<0.05 OCR vs O). Citrate synthase activity and MAPR were lower in both O and OCR than Y (P<0.05). UCP3 protein level was higher in soleus and plantaris muscles from O rats than Y and OCR (p<0.005). CR lowered UCP3 expression in skeletal muscles to the level in Y rats (p<0.005 OCR vs O). CR also lowered expression of mRNA levels of NADH4 (p<0.005 OCR vs O). NEA levels were lower in O and OCR rats than in Y (p<0.05 Y vs O and OCR). In conclusion, the decline in mitochondrial functions during aging can be counteracted by CR but an age‐related decline in activity levels could not be prevented. Funded by NIH RO1 AG09531 and Mayo Foundation.

Background Sedentary time has been shown to have deleterious effects on health. Today's workforce spends most of the day sitting. The objective of this study was to evaluate the effect of workplace interventions to decrease sedentary time on cardiometabolic risk factors. Methods Sedentary office workers (n=127; ages 22‐64; BMI=28.5±6.1 kg/m 2 ) were recruited from three Minnesota employers and randomized to one of four intervention groups for 6 months: 1) Control, 2) Move (蠅30 min of light activity during the workday), 3) Stand (standing 蠅50% of the workday using a sit‐stand workstation), or 4) Stand+Move (combined Stand and Move). A 'metabolic risk score' (MRS) was calculated at baseline and 6 months using the following cardiometabolic risk factors: blood pressure, fasting blood glucose, log of fasting triglycerides, and HDL‐cholesterol. A z‐score was computed for each risk factor for each subject [(subject value – sample mean)/sample SD]. The MRS was derived by summing the z‐scores (HDL‐z subtracted). Results There was a significant intervention effect on MRS (p<.01). A seasonal time trend was observed, with MRS increasing significantly in Control and Move groups (p<.001), but not for the Stand and Stand+Move. Results (mean±se) are shown in Figure 1. Conclusions Sit‐stand workstations combined with an intervention to increase light physical activity at work may be an effective tool to improve cardiometabolic risk. image

The thermic effect of food (TEF) is partially mediated by β‐adrenergic receptors (βAR) and is an important component of daily energy expenditure. Greater sympathetic activity has been associated with decreased BAR responsiveness. We hypothesized that muscle sympathetic nerve activity (MSNA) would be inversely correlated with the βAR component of TEF (TEF β ). We measured MSNA (microneurography) and energy expenditure (EE) (indirect calorimetry) before and for 5 h after a mixed meal (40% daily EE). Measurements were made during systemic βAR blockade with propranolol (BB) and saline (NS) infusion on separate days in 10 healthy subjects (2 female, age 28±2 y, BMI 24.4±0.6 kg/m 2 ). Resting MSNA was 39±3 bursts/100 heartbeats (hb). Within 1 h after the meal, MSNA significantly increased during both NS (12±3 bursts/100 hb) and BB (18±4) but was not significantly different between the two days, (P=0.375). The maximum increase in REE after the meal was 269±29 (NS) and 198±22 (BB) kcal/24 h (P<0.05). TEF β (TEF β = AUC TEF NS – AUC TEF BB ) was 48±20% of total TEF. TEF β was positively correlated with resting MSNA (R 2 =0.70, P<0.05). Contrary to our hypothesis, we found that greater levels of MSNA were associated with greater TEF β . These results indicated that resting MSNA may be an important contributor to daily energy expenditure. Studies are needed to determine if greater MSNA is associated with a resistance to weight gain. The project described was supported by the Mayo Foundation for Medical Education and Research and NIH Grant Numbers K23 DK82424, P30 DK50456, and UL1 RR024150.

BACKGROUND: Prolonged sitting has been shown to increase mortality and obesity. OBJECTIVE: We sought to determine whether physicians would use a treadmill desk, increase their daily physical activity and lose weight. PARTICIPANTS: 20 overweight and obese physicians aged 25 to 70 with Body Mass Index > 25. METHODS: Participants used a treadmill desk, a triaxial accelerometer, and received exercise counseling in a randomized, cross-over trial over 24 weeks. Group 1 received exercise counseling, accelerometer feedback, and a treadmill desk for 12 weeks and then accelerometer only for 12 weeks. Group 2 received an accelerometer without feedback for 12 weeks followed by exercise counseling, accelerometer feedback, and the treadmill desk for 12 weeks. RESULTS: Daily physical activity increased while using the treadmill desk compared to not using the desk by 197 kcal per day (p=0.003). The difference in weight during the two 12 week periods was 1.85 kg (p=0.03). Percent body fat was 1.9% lower while using the treadmill desk (p=0.02). There were no differences in metabolic or well-being measures. CONCLUSIONS: This study suggests that physicians will use a treadmill desk, that it does increase their activity, and that it may help with weight loss. Further studies are warranted.

Objectives: This systematic review evaluated the accuracy of triaxial and omnidirectional accelerometers for measuring physical activity and sedentary behavior in children. Design: Systematic review of the literature. Methods: We comprehensively searched several databases for studies published from January 1996 through June 2018 that reported diagnostic accuracy measures in children and adolescents (age 3-18 years) and compared accelerometers with energy expenditure using indirect calorimetry. Results: We included 11 studies that enrolled 570 participants. All studies used indirect calorimetry as the reference standard. Across the studies, median sensitivity ranged from 46% to 96% and median specificity ranged from 71% to 96%. Median area under the curve ranged from 69% to 98%. Conclusions: Accuracy measures were greatest when detecting sedentary behavior and lowest when detecting light physical activity. Accuracy was higher when the accelerometer was placed on the hip compared with the wrist. The current evidence suggests that triaxial and omnidirectional accelerometers are accurate in measuring sedentary behavior and physical activity levels in children.