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.

Daily energy expenditure through the human life course

Total daily energy expenditure (“total expenditure”) reflects daily energy needs and is a critical variable in human health and physiology, but its trajectory over the life course is poorly studied. We analyzed a large, diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 years. Total expenditure increased with fat-free mass in a power-law manner, with four distinct life stages. Fat-free mass–adjusted expenditure accelerates rapidly in neonates to ~50% above adult values at ~1 year; declines slowly to adult levels by ~20 years; remains stable in adulthood (20 to 60 years), even during pregnancy; then declines in older adults. These changes shed light on human development and aging and should help shape nutrition and health strategies across the life span.

Dietary Macronutrient and Micronutrient Intake over a 7-Day Period in Female Varsity Ice Hockey Players

This study examined the energy, macronutrient, and micronutrient intakes of female ice hockey players over a 7-d period including game, practice, and rest days. Twenty-three female varsity players (19.0 ± 1.1 yr, 167.1 ± 6.5 cm, 67.0 ± 8.0 kg) volunteered for the study. Average total daily energy expenditure (TDEE) was estimated over the 7-day period. Average 7-day energy intake (EI) and TDEE were 2354 ± 353 and 2304 ± 204 kcal. The majority (n = 19) of athletes had an EI ≥ 90% of their estimated TDEE. Macronutrient intake was 52% carbohydrate (CHO), 32% fat, and 16% protein of total EI, although CHO intake was slightly below recommendations (5 g/kg BM/d) on game and practice (4.8 ± 1.4 and 4.5 g/kg BM/d) days. Game day EI was greater than practice and rest days. Recommended micronutrient intakes were not met by most athletes for iron, calcium, vitamin D, and potassium, and intakes were similar between game, practice, and rest days. In summary, the average EI for female varsity ice hockey players appeared adequate to meet their energy needs over a weekly cycle of game, practice, and rest days. However, these female athletes would benefit from increasing CHO intake on game and practice days and selecting foods that are rich in vitamins and minerals.

Schweres Lungenemphysem: Zusammenhänge zwischen klinischen Verläufen nach bronchoskopischer Volumenreduktion und metabolischen Parametern erkennen

<b>Background:</b> Hypermetabolism and muscle wasting frequently occur in patients with severe emphysema. Improving respiratory mechanics by bronchoscopic lung volume reduction (BLVR) might contribute to muscle maintenance by decreasing energy requirements and alleviating eating-related dyspnoea. <b>Objective:</b> The goal was to assess the impact of BLVR on energy balance regulation. <b>Design:</b> Twenty emphysematous subjects participated in a controlled clinical experiment before and 6 months after BLVR. Energy requirements were assessed: basal metabolic rate (BMR) by ventilated hood, total daily energy expenditure (TDEE) by doubly labelled water, whole body fat-free mass (FFM) by deuterium dilution, and physical activity by accelerometry. Oxygen saturation, breathing rate, and heart rate were monitored before, during, and after a standardized meal via pulse oximetry and dyspnoea was rated. <b>Results:</b> Sixteen patients completed follow-up, and among those, 10 patients exceeded the minimal clinically important difference of residual volume (RV) reduction. RV was reduced with median (range) 1,285 mL (–2,430, –540). Before BLVR, 90% of patients was FFM-depleted despite a normal BMI (24.3 ± 4.3 kg/m2). BMR was elevated by 130%. TDEE/BMR was 1.4 ± 0.2 despite a very low median (range) daily step count of 2,188 (739, 7,110). Following BLVR, the components of energy metabolism did not change significantly after intervention compared to before intervention, but BLVR treatment decreased meal-related dyspnoea (4.1 vs. 1.7, <i>p</i> = 0.019). <b>Conclusions:</b> Impaired respiratory mechanics in hyperinflated emphysematous patients did not explain hypermetabolism. <b>Clinical Trial Registry Number:</b> NCT02500004 at www.clinicaltrial.gov.

Concepts of indirect calorimetry on metabolic disorders: a narrative review

Introduction: Indirect calorimetry remains a gold standard in measuring resting energy expenditure in the clinical field. Through its measurements, it is possible to offers a patient’s energy needs to maximize nutritional therapy benefits. However, the concepts and methodological basis of collected data can be difficult to be interpreted by users in clinical practice. Objective: To address the concepts of total daily energy expenditure and its components and present the methodological aspects of indirect calorimetry that can guide the clinical field. Method: Narrative bibliographic review using the electronic Pubmed (US National Library of Medicine), SCOPUS, and Scientific Electronic Library Online (SCIELO) databases. The research was carried out in the period between 1905-2019, using the following identifiers in Health Sciences Descriptors: Basal Metabolism, Energy Metabolism and Indirect Calorimetry. We selected 55 researches published that presented contents related to the objectives of this study. Result: The total daily energy expenditure (TDEE) is comprised of three main components, such as physical activity (PA), thermic effect of food (TEF) and basal metabolic rate (BMR) and/or resting energy expenditure (REE). The REE is generally evaluated by indirect calorimetry, which also provides information on the respiratory coefficient (RQ) or oxidation of substrates. Its result varies depending on the existence of some metabolic disorders such as obesity or malnutrition. Therefore, the proper management of the methodological aspects of indirect calorimetry and its subsequent interpretation in metabolic disorders is essential to guarantee the results’ quality. Conclusion: Energy expenditure concepts and the methodological basis of indirect calorimetry are relevant to providing individualized attention to patients with metabolic disorders. This review can be used as a practical guide, helping to understand the correct application of the indirect calorimetry technique in studies related to energy expenditure with an emphasis on metabolic disorders.

Energy deficit increases hepcidin and exacerbates declines in dietary iron absorption following strenuous physical activity: a randomized-controlled cross-over trial

ABSTRACT Background Strenuous physical activity promotes inflammation and depletes muscle glycogen, which may increase the iron regulatory hormone hepcidin. Hepcidin reduces dietary iron absorption and may contribute to declines in iron status frequently observed following strenuous physical activity. Objectives To determine the effects of strenuous physical activity on hepcidin and dietary iron absorption and whether energy deficit compared with energy balance modifies those effects. Methods This was a randomized, cross-over, controlled-feeding trial in healthy male subjects (n = 10, mean ± SD age: 22.4 ± 5.4 y, weight: 87.3 ± 10.9 kg) with sufficient iron status (serum ferritin 77.0 ± 36.7 ng/mL). Rest measurements were collected before participants began a 72-h simulated sustained military operation (SUSOPS), designed to elicit high energy expenditure, glycogen depletion, and inflammation, followed by a 7-d recovery period. Two 72-h SUSOPS trials were performed where participants were randomly assigned to consume either energy matched (±10%) to their individual estimated total daily energy expenditure (BAL) or energy at 45% of total daily energy expenditure to induce energy deficit (DEF). On the rest day and at the completion of BAL and DEF, participants consumed a beverage containing 3.8 mg of a stable iron isotope, and plasma isotope appearance was measured over 6 h. Results Muscle glycogen declined during DEF and was preserved during BAL (−188 ± 179 mmol/kg, P-adjusted &lt; 0.01). Despite similar increases in interleukin-6, plasma hepcidin increased during DEF but not BAL, such that hepcidin was 108% greater during DEF compared with BAL (7.8 ± 12.2 ng/mL, P-adjusted &lt; 0.0001). Peak plasma isotope appearance at 120 min was 74% lower with DEF (59 ± 38% change from 0 min) and 49% lower with BAL (117 ± 81%) compared with rest (230 ± 97%, P-adjusted &lt; 0.01 for all comparisons). Conclusions Strenuous physical activity decreases dietary iron absorption compared with rest. Energy deficit exacerbates both the hepcidin response to physical activity and declines in dietary iron absorption compared with energy balance. This trial was registered at clinicaltrials.gov as NCT03524690.

Energy Intake and Total Daily Energy Expenditure Assessed by Subjective and Objective Methods in Older Individuals from a Tropical Setting in Brazil

Objectives To assess different methods of estimating energy balance (EB) and its components in a sample of older people (age ≥ 60 years) living in a tropical city in Brazil. Methods EB was calculated in 85 older individuals (69 women) as the difference between energy intake (EI), obtained by three 24-hour dietary recalls on nonconsecutive days, and total daily energy expenditure (TDEE) estimated by 24-hour physical activity recalls (24hPAR, subjective method) and accelerometry (ACC, objective method) on the same days. Basal metabolic rate (BMR) was estimated by a validated local predictive equations derived from a sample of healthy adults from the same city and by international equations (Schofield). Resting energy expenditure (MET) was also estimated by local predictive equation and the conventional value of 3.5 mL.kg−1.min−1. Anthropometry and % body fat (DXA) assessment was also obtained. Results Mean (SD) age was 69.0 (5.5) years with a mean BMI of 26.7 (4.4) kg.m−2 and %BF of 39.4 (7.9). BMR from locally-derived equations (1050.7 ± 188.7 kcal.day−1) was significantly lower than BMR estimated by the Schofield's equation (1286.5 ± 145.3 kcal.day−1). Likewise, predicted MET was significantly lower than the conventional value. Despite the high prevalence of overweight (66% with BMI ≥ 25 kg.m−2), EB was always negative for the 24hPAR method (−863.5 ± 799.5 kcal.day−1) but positive (252.1 ± 726.6 kcal.day−1) with the ACC method when MET was calculated with population-specific equations. EB estimated by ACC was also negative (−122.7 ± 781.0 kcal.day−1) using the conventional MET value. Conclusions The findings of this study indicate that EB is negative when the subjective method of TDEE estimation is used but becomes positive with the objective method. It is also evident that BMR and MET equations derived from samples of the population of interest may help improve the final estimates of TDEE and EB in older adults. Funding Sources CNPq (310,461/2016–20 and 485,168/2011–1) and FAPERJ (E-26/111.496/2011; E-26/202.514/2018; E-26/203.068/2017).