Iron chelation increases beige fat differentiation and metabolic activity, preventing and treating obesity

Beige and brown fat consume glucose and lipids to produce heat, using uncoupling protein 1 (UCP1). It is thought that full activation of brown adipose tissue (BAT) may increase total daily energy expenditure by 20%. Humans normally have more beige and potentially beige-able fat than brown fat. Strategies to increase beige fat differentiation and activation may be useful for the treatment of obesity and diabetes. Mice were fed chow or high-fat diet (HFD) with or without the iron chelator deferasirox. Animals fed HFD + deferasirox were markedly lighter than their HFD controls with increased energy expenditure (12% increase over 24 h, p < 0.001). Inguinal fat from HFD + deferasirox mice showed increased beige fat quantity with greater Ucp1 and Prdm16 expression. Inguinal adipose tissue explants were studied in a Seahorse bioanalyser and energy expenditure was significantly increased. Deferasirox was also effective in established obesity and in ob/ob mice, indicating that intact leptin signalling is not needed for efficacy. These studies identify iron chelation as a strategy to preferentially activate beige fat. Whether activating brown/beige fat is effective in humans is unproven. However, depleting iron to low-normal levels is a potential therapeutic strategy to improve obesity and related metabolic disorders, and human studies may be warranted.

Effect of Weight Self-Stigma and Self-Esteem on Aerobic Exercise Capacity in Adult Women with Different Body Compositions

Background: Overweight individuals face weight-related stigmatization, driving self-exclusion from exercise and physical activity. The extent to which weight self-stigma and self-esteem are associated with aerobic capacity remains unclear. Therefore, this study aimed to characterize the cardiopulmonary fitness, weight self-stigma, and self-esteem of overweight women and examine whether weight self-stigma and self-esteem predict cardiopulmonary aerobic capacity. Methods: A cross-sectional study was conducted with 66 women stratified into two groups: a normal weight (NW) group and an overweight (OW) group. The mean body mass indexes and ages of the NW and OW groups were 20.4 ± 0.36 kg/m2 and 29.5 ± 0.8 kg/m2, and 24 ± 7 years and 21 ± 3 years, respectively. Submaximal exercise testing using the modified Bruce treadmill protocol was conducted to measure the predicted oxygen uptake (VO2 peak) and energy expenditure. The Weight Self-Stigma Questionnaire and the Rosenberg Self-Esteem Scale were used. Results: Significantly lower mean of predicted VO2 peak and higher mean of energy expenditure were reported in the OW group compared with the NW group (25.8 ± 5.3 mL/kg/min vs. 28.7 ± 4.8 mL/kg/min, p = 0.001 and 9.7 ± 1.9 kcal/min vs. 7.5 ± 1.8 kcal, p = 0.03, respectively). There was a significant difference in weight self-stigma and self-esteem between the groups. Regression model analysis indicated that weight self-stigma and self-esteem explained 45% of the variance in the predicted VO2 peak. Conclusion: Strategies enhancing self-esteem and avoiding stigmatization should be embraced to promote fitness and engagement in physical activity among OW women.

EXPRESS: “Run to the hills”: Specific contributions of anticipated energy expenditure during active spatial learning

Grounded views of cognition consider that space perception is shaped by the body and its potential for action. These views are substantiated by observations such as the distance-on-hill effect, described as the overestimation of visually perceived uphill distances. An interpretation of this phenomenon is that slanted distances are overestimated because of the integration of energy expenditure cues. The visual perceptual processes involved are however usually tackled through explicit estimation tasks in passive situations. The goal of this study was to consider instead more ecological active spatial processing. Using immersive virtual reality and an omnidirectional treadmill, we investigated the effect of anticipated implicit physical locomotion cost by comparing spatial learning for uphill and downhill routes, while maintaining actual physical cost and walking speed constant. In the first experiment, participants learnt city layouts by exploring uphill or downhill routes. They were then tested using a landmark positioning task on a map. In the second experiment, the same protocol was used with participants who wore loaded ankle weights. Results from the first experiment showed that walking uphill routes led to a global underestimation of distances compared to downhill routes. This inverted distance-of-hill effect was not observed in the second experiment, where an additional effort was applied. These results suggest that the underestimation of distances observed in experiment one emerged from recalibration processes whose function was to solve the transgression of proprioceptive predictions linked with uphill energy expenditure. Results are discussed in relation to constructivist approaches on spatial representations and predictive coding theories.

Resting costs too: the relative importance of active and resting energy expenditure in a sub-arctic seabird

Breeding is costly for many animals, including birds that must deliver food to a central place (i.e. nest). Measuring energy expenditure throughout the breeding season can provide valuable insights on physiological limitations by highlighting periods of high demands, and ultimately allows to improve conservation strategies. However, quantifying energy expenditure in wildlife can be challenging, as existing methods do not measure both active (e.g. foraging) and resting energy costs across short and long time scales. Here, we develop a novel method for comparing active and resting costs in 66 pre-breeding and breeding seabirds (black-legged kittiwakes; Rissa tridactyla) by combining accelerometry and triiodothyronine (T3), as proxies for active and resting costs, respectively. Activity energy costs were higher during incubation (p=0.0004) and chick-rearing (p&lt;0.0001) compared to pre-laying, due to an increase in time spent in flight of 11% (p=0.0005) and 15% (p&lt;0.0001), respectively. Levels of T3, reflecting resting costs, peaked marginally during incubation with an average concentration of 4.71±1.97 pg mL−1 in comparison to 2.66±1.30 pg mL−1 in pre-laying (p=0.05), and 3.16±2.85 pg mL−1 in chick-rearing (p=11). Thus, although chick-rearing is often assumed to be the costliest breeding stage by multiple studies, our results suggest that incubation could be more costly due to high resting costs. We highlight the importance of accounting for both active and resting costs when assessing energy expenditure.

Dynamic body acceleration as a proxy to predict the cost of locomotion in bottlenose dolphins

Estimates of the energetic costs of locomotion (COL) at different activity levels are necessary to answer fundamental eco-physiological questions and to understand the impacts of anthropogenic disturbance to marine mammals. We combined estimates of energetic costs derived from breath-by-breath respirometry with measurements of overall dynamic body acceleration (ODBA) from biologging tags to validate ODBA as a proxy for COL in trained common bottlenose dolphins (Tursiops truncatus). We measured resting metabolic rate (RMR); mean individual RMR was 0.71-1.42 times that of a similarly sized terrestrial mammal and agreed with past measurements which used breath-by-breath and flow-through respirometry. We also measured energy expenditure during submerged swim trials, at primarily moderate exercise levels. We subtracted RMR to obtain COL, and normalized COL by body size to incorporate individual swimming efficiencies. We found both mass-specific energy expenditure and mass-specific COL were linearly related with ODBA. Measurements of activity level and cost of transport (the energy required to move a given distance) improve understanding of the costs of locomotion in marine mammals. The strength of the correlation between ODBA and COL varied among individuals, but the overall relationship can be used at a broad scale to estimate the energetic costs of disturbance, daily locomotion costs to build energy budgets, and investigate the costs of diving in free-ranging animals where bio-logging data are available. We propose that a similar approach could be applied to other cetacean species.

ACE2 pathway regulates thermogenesis and energy metabolism

Identification of key regulators of energy homeostasis holds important therapeutic promise for metabolic disorders, such as obesity and diabetes. ACE2 cleaves angiotensin II (Ang II) to generate Ang-(1-7) which acts mainly through the Mas1 receptor. Here, we identify ACE2 pathway as a critical regulator in the maintenance of thermogenesis and energy expenditure. We found that ACE2 is highly expressed in brown adipose tissue (BAT) and that cold stimulation increases ACE2 and Ang-(1-7) levels in BAT and serum. Ace2 knockout mice (Ace2-/y) and Mas1 knockout mice (Mas1-/-) displayed impaired thermogenesis. Mice transplanted with brown adipose tissue from Mas1-/- display metabolic abnormalities consistent with those seen in the Ace2 and Mas1 knockout mice. In contrast, impaired thermogenesis of Leprdb/db obese diabetic mice and high-fat diet-induced obese mice were ameliorated by overexpression of Ace2 or continuous infusion of Ang-(1-7). Activation of ACE2 pathway was associated with improvement of metabolic parameters, including blood glucose, lipids and energy expenditure in multiple animal models. Consistently, ACE2 pathway remarkably enhanced the browning of white adipose tissue. Mechanistically, we showed that ACE2 pathway activated Akt/FoxO1 and PKA pathway, leading to induction of UCP1 and activation of mitochondrial function. Our data propose that adaptive thermogenesis requires regulation of ACE2 pathway and highlight novel potential therapeutic targets for the treatment of metabolic disorders.