Human Skeletal Muscle Mitochondrial Uncoupling Is Associated with Cold Induced Adaptive Thermogenesis

Background: Mild cold exposure and overfeeding are known to elevate energy expenditure in mammals, including humans. This process is called adaptive thermogenesis. In small animals, adaptive thermogenesis is mainly caused by mitochondrial uncoupling in brown adipose tissue and regulated via the sympathetic nervous system. In humans, skeletal muscle is a candidate tissue, known to account for a large part of the epinephrine-induced increase in energy expenditure. However, mitochondrial uncoupling in skeletal muscle has not extensively been studied in relation to adaptive thermogenesis in humans. Therefore we hypothesized that cold-induced adaptive thermogenesis in humans is accompanied by an increase in mitochondrial uncoupling in skeletal muscle. Methodology/Principal Findings: The metabolic response to mild cold exposure in 11 lean, male subjects was measured in a respiration chamber at baseline and mild cold exposure. Skeletal muscle mitochondrial uncoupling (state 4) was measured in muscle biopsies taken at the end of the respiration chamber stays. Mild cold exposure caused a significant increase in 24h energy expenditure of 2.8 % (0.32 MJ/day, range of 20.21 to 1.66 MJ/day, p,0.05). The individual increases in energy expenditure correlated to state 4 respiration (p,0.02, R 2 = 0.50). Conclusions/Significance: This study for the first time shows that in humans, skeletal muscle has the intrinsic capacity for cold induced adaptive thermogenesis via mitochondrial uncoupling under physiological conditions. This opens possibilitie

Ethnic differences in resting metabolic rate, respiratory quotient and body temperature: a comparison of Africans and European Australians

Purpose: A comparison of resting metabolic rate (RMR), respiratory quotient (RQ) and body temperature between adults of African and European descent. Method: Twenty-nine sub-Saharan Africans (SSA; 13 men and 16 women) and thirty-two Australians of European descent (EUR; eight men and 24 women) had RMR and RQ measured by indirect calorimetry. Dual-energy X-ray absorptiometry was used to determine fat mass (FM), fat-free mass, bone mineral content (BMC), appendicular lean tissue mass and non-appendicular lean tissue mass. Total skeletal muscle mass (SMM) was predicted. Residual mass (RM) was the difference between body weight and the sum of FM, SMM and BMC. The short form of the International Physical Activity Questionnaire was used to determine habitual physical activity (PA). Tympanic in the ear temperature (IET) and forearm to fingertip temperature gradients (FFG) were monitored throughout the protocol. Results: The unadjusted RMR of SSA was significantly lower compared to EUR. Adjusted for age, sex, season, PA, FM, BMC, SMM and RM, this difference in RMR was still evident (mean ± SE, SSA: 4880 ± 161 kJ/d vs. EUR: 5979 ± 111, P < 0.005). The same model of adjustment also uncovered a significantly lower adjusted IET (SSA: 35.26 °C ± 0.133 vs. EUR: 35.60 ± 0.091, P < 0.05), a higher adjusted RQ (SSA: 0.86 ± 0.014 vs. EUR: 0.83 ± 0.010, P < 0.05) but no difference in adjusted FFG. Conclusions: In this study, SSA had a lower RMR, higher RQ and lower IET relative to EUR Australians

Fasting and glucose induced thermogenesis in response to three ambient temperatures: a randomized crossover trial in the metabolic syndrome

Background/objectives: Cold exposure increases thermogenesis and could improve insulin sensitivity. We hypothesized a blunted response in the metabolic syndrome (MetS). Subjects/methods: Twenty older adults 59 ± 10.4 years (with MetS, MetS+, n = 9; without MetS, MetS−, n = 11) completed a randomized crossover design of 3.5 h exposures to 20, 25 and 27 °C on three visits. After an hour’s rest at the desired temperature, resting metabolic rate (RMR), respiratory quotient (RQ), forearm to fingertip gradients (FFG), and in the ear temperature (IET) were measured over 30 min. An oral glucose tolerance test followed, and serial measurements were continued for 2 h. Venous blood was sampled for clinical chemistry, irisin, and fibroblast growth factor 21(FGF21). A mixed model ANCOVA adjusted data for age, gender, fat mass, fat-free mass and seasonality. Results: There was a significant MetS×temperature interaction where adjusted RMR was significantly higher in MetS+ compared to MetS− by 12% at 20 °C and by 6% at 25 °C, but similar at 27 °C. FFG increased and IET decreased with decreasing temperature to the same extent in both groups. Fasting irisin and FGF21 did not vary with temperature but the former was significantly higher in MetS−. Adjusted postprandial RQ and insulin to glucose ratios were significantly higher at 20 °C relative to 25 °C. Partial correlation analysis of differences between 27 and 20 °C indicated significant positive relationships between fasting as well as postprandial RQ and the respective changes in irisin and FGF21. Conclusions: There could be an upward shift of the TNZ in MetS+, but this needs reevaluation