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1.
Revisiting preeclampsia: a metabolic disorder of the placenta.
Hu, M, Li, J, Baker, PN, Tong, C
The FEBS journal. 2022;(2):336-354
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Abstract
Preeclampsia (PE) is a leading cause of maternal and neonatal mortality and morbidity worldwide, impacting the long-term health of both mother and offspring. PE has long been characterized by deficient trophoblast invasion into the uterus and consequent placental hypoperfusion, yet the upstream causative factors and effective interventional targets for PE remain unknown. Alterations in the metabolism of preeclamptic placentas are thought to result from placental ischemia, while disturbances of the metabolism and of metabolites in PE pathogenesis are largely ignored. In fact, as one of the largest fetal organs at birth, the placenta consumes a considerable amount of glucose and fatty acid. Increasing evidence suggests glucose and fatty acid exist as energy substrates and regulate placental development through bioactive derivates. Moreover, recent findings have revealed that the placental metabolism adapts readily to environmental changes, altering its response to nutrients and endocrine signals; this adaptability optimizes pregnancy outcomes by diversifying available carbon sources for energy production, hormone synthesis, angiogenesis, immune activation, and tolerance, and fetoplacental growth. These observations raise the possibility that carbohydrate and lipid metabolism abnormalities play a role in both the etiology and clinical progression of PE, sparking a renewed interest in the interrelationship between PE and metabolic dysregulation. This review will focus on key metabolic substrates and regulatory molecules in the placenta and aim to provide novel insights with respect to the metabolism's role in modulating placental development and functions. Further investigations from this perspective are poised to decipher the etiology of PE and suggest potential therapies.
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Mobile Phone Radiation Deflects Brain Energy Homeostasis and Prompts Human Food Ingestion.
Wardzinski, EK, Jauch-Chara, K, Haars, S, Melchert, UH, Scholand-Engler, HG, Oltmanns, KM
Nutrients. 2022;(2)
Abstract
Obesity and mobile phone usage have simultaneously spread worldwide. Radio frequency-modulated electromagnetic fields (RF-EMFs) emitted by mobile phones are largely absorbed by the head of the user, influence cerebral glucose metabolism, and modulate neuronal excitability. Body weight adjustment, in turn, is one of the main brain functions as food intake behavior and appetite perception underlie hypothalamic regulation. Against this background, we questioned if mobile phone radiation and food intake may be related. In a single-blind, sham-controlled, randomized crossover comparison, 15 normal-weight young men (23.47 ± 0.68 years) were exposed to 25 min of RF-EMFs emitted by two different mobile phone types vs. sham radiation under fasting conditions. Spontaneous food intake was assessed by an ad libitum standard buffet test and cerebral energy homeostasis was monitored by 31phosphorus-magnetic resonance spectroscopy measurements. Exposure to both mobile phones strikingly increased overall caloric intake by 22-27% compared with the sham condition. Differential analyses of macronutrient ingestion revealed that higher calorie consumption was mainly due to enhanced carbohydrate intake. Measurements of the cerebral energy content, i.e., adenosine triphosphate and phosphocreatine ratios to inorganic phosphate, displayed an increase upon mobile phone radiation. Our results identify RF-EMFs as a potential contributing factor to overeating, which underlies the obesity epidemic. Beyond that, the observed RF-EMFs-induced alterations of the brain energy homeostasis may put our data into a broader context because a balanced brain energy homeostasis is of fundamental importance for all brain functions. Potential disturbances by electromagnetic fields may therefore exert some generalized neurobiological effects, which are not yet foreseeable.
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Analysis of sex-based differences in energy substrate utilization during moderate-intensity aerobic exercise.
Cano, A, Ventura, L, Martinez, G, Cugusi, L, Caria, M, Deriu, F, Manca, A
European journal of applied physiology. 2022;(1):29-70
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Abstract
PURPOSE To explore sex-based differences in energy substrate utilization during moderate-intensity aerobic exercise; to identify the underpinning candidate physiological mechanisms. METHODS Three databases were searched from inception to August 2020. Pertinent studies quantifying the utilization of substrates during moderate aerobic exercise in healthy men and reproductive-age women were considered. Studies conducted on sedentary/recreationally active and athletic populations were included and analyzed separately. RESULTS Thirty-five studies entered the meta-analysis (21 in sedentary/recreationally active, 14 in athletic populations). Compared to women, the respiratory exchange ratio was significantly higher both in sedentary (mean difference, MD: + 0.03; p < 0.00001) and athletic men (MD: + 0.02; p < 0.0001). Greater carbohydrate oxidation was observed both in sedentary (standardized MD, SMD: 0.53; p = 0.006) and athletic men (SMD: 1.24; p < 0.00001). Regarding lipid substrates, sedentary men oxidized less fat than women (SMD: - 0.77; p = 0.0002), while no sex-based differences in fat oxidation were observed in athletes (SMD: 0.06; p = 0.77). Paucity of data prevented robust meta-analyses for protein sources. Sex hormones and different adrenergic activation were the most cited mechanisms to discuss sex-based differences. CONCLUSIONS Meta-analyses confirmed that men display greater reliance on carbohydrates while women rely more on lipids to sustain moderate aerobic exercise. The latter finding was not confirmed in athletes, a novel aspect of the present study. Mechanistically driven research is needed to further dissect the physiological underpinnings of sex differences in substrate utilization during aerobic exercise, especially for proteins, which are still less investigated than other substrates.
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Prevalence of Triad-RED-S symptoms in high-level Kenyan male and female distance runners and corresponding control groups.
Õnnik, L, Mooses, M, Suvi, S, Haile, DW, Ojiambo, R, Lane, AR, Hackney, AC
European journal of applied physiology. 2022;(1):199-208
Abstract
PURPOSE This study examined and compared select Triad-RED-S components/risk factors in high-level Kenyan male and female distance runners to corresponding control groups; focusing on examining energy intake (EI), bone indices, and hormonal markers. METHODS A cross-sectional, observational design was used in which Kenyan male and female (n = 30 and n = 26, respectively) middle- and long-distance runners and corresponding male and female control groups (n = 29 and n = 29, respectively) were examined. The participant's bone mineral density (BMD) at the lumbar spine, right femur, and total body were measured using a dual-energy X-ray absorptiometry analysis. Complete blood counts (CBC) were done on the whole blood specimens and hormonal measurements were performed on plasma specimens. In addition, athletes completed metabolic testing to determine maximal oxygen uptakes and 7-day dietary diaries. RESULTS Overall daily EI across runners and controls within each sex were low, but not significantly different (p > 0.05). Prevalence of low BMD values (Z score < - 2.0) was comparable across groups in each sex (p > 0.05). CBC measures suggested that both runners and controls were healthy. Finally, slight hormonal differences between runners and their respective controls existed (p < 0.05), but were not clinically meaningful or observed in typical Triad-RED-S-related parameters. CONCLUSION High-level Kenyan male and female runners had low daily EI, but no tendency toward a higher prevalence of low BMD, or Triad-RED-S-related hormonal abnormalities. The occurrence of low EI was not a major risk factor in our athletes; this calls into question whether the current criteria for Triad-RED-S are entirely applicable for athletes of African ethnicity.
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The acute effect of fasted exercise on energy intake, energy expenditure, subjective hunger and gastrointestinal hormone release compared to fed exercise in healthy individuals: a systematic review and network meta-analysis.
Frampton, J, Edinburgh, RM, Ogden, HB, Gonzalez, JT, Chambers, ES
International journal of obesity (2005). 2022;(2):255-268
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Abstract
OBJECTIVE To determine the acute effect of fasted and fed exercise on energy intake, energy expenditure, subjective hunger and gastrointestinal hormone release. METHODS CENTRAL, Embase, MEDLINE, PsycInfo, PubMed, Scopus and Web of Science databases were searched to identify randomised, crossover studies in healthy individuals that compared the following interventions: (i) fasted exercise with a standardised post-exercise meal [FastEx + Meal], (ii) fasted exercise without a standardised post-exercise meal [FastEx + NoMeal], (iii) fed exercise with a standardised post-exercise meal [FedEx + Meal], (iv) fed exercise without a standardised post-exercise meal [FedEx + NoMeal]. Studies must have measured ad libitum meal energy intake, within-lab energy intake, 24-h energy intake, energy expenditure, subjective hunger, acyl-ghrelin, peptide YY, and/or glucagon-like peptide 1. Random-effect network meta-analyses were performed for outcomes containing ≥5 studies. RESULTS 17 published articles (23 studies) were identified. Ad libitum meal energy intake was significantly lower during FedEx + Meal compared to FedEx + NoMeal (MD: -489 kJ; 95% CI, -898 to -80 kJ; P = 0.019). Within-lab energy intake was significantly lower during FastEx + NoMeal compared to FedEx + NoMeal (MD: -1326 kJ; 95% CI, -2102 to -550 kJ; P = 0.001). Similarly, 24-h energy intake following FastEx + NoMeal was significantly lower than FedEx + NoMeal (MD: -2095 kJ; 95% CI, -3910 kJ to -280 kJ; P = 0.024). Energy expenditure was however significantly lower during FastEx + NoMeal compared to FedEx+NoMeal (MD: -0.67 kJ/min; 95% CI, -1.10 to -0.23 kJ/min; P = 0.003). Subjective hunger was significantly higher during FastEx + Meal (MD: 13 mm; 95% CI, 5-21 mm; P = 0.001) and FastEx + NoMeal (MD: 23 mm; 95% CI, 16-30 mm; P < 0.001) compared to FedEx + NoMeal. CONCLUSION FastEx + NoMeal appears to be the most effective strategy to produce a short-term decrease in energy intake, but also results in increased hunger and lowered energy expenditure. Concerns regarding experimental design however lower the confidence in these findings, necessitating future research to rectify these issues when investigating exercise meal timing and energy balance. PROSPERO REGISTRATION NUMBER CRD42020208041. KEY POINTS Fed exercise with a standardised post-exercise meal resulted in the lowest energy intake at the ad libitum meal served following exercise completion. Fasted exercise without a standardised post-exercise meal resulted in the lowest within-lab and 24-h energy intake, but also produced the lowest energy expenditure and highest hunger. Methodological issues lower the confidence in these findings and necessitate future work to address identified problems.
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Effect of oral contraceptives on energy balance in women: A review of current knowledge and potential cellular mechanisms.
Metz, L, Isacco, L, Redman, LM
Metabolism: clinical and experimental. 2022;:154919
Abstract
Body weight management is currently of major concern as the obesity epidemic is still a worldwide challenge. As women face more difficulties to lose weight than men, there is an urgent need to better understand the underlying reasons and mechanisms. Recent data have suggested that the use of oral contraceptive (OC) could be involved. The necessity of utilization and development of contraceptive strategies for birth regulation is undeniable and contraceptive pills appear as a quite easy approach. Moreover, OC also represent a strategy for the management of premenstrual symptoms, acne or bulimia nervosa. The exact impact of OC on body weight remains not clearly established. Thus, after exploring the potential underlying mechanisms by which OC could influence the two side of energy balance, we then provide an overview of the available evidence regarding the effects of OC on energy balance (i.e. energy expenditure and energy intake). Finally, we highlight the necessity for future research to clarify the cellular effects of OC and how the individualization of OC prescriptions can improve long-term weight loss management.
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Model systems for studying polyphosphate biology: a focus on microorganisms.
Denoncourt, A, Downey, M
Current genetics. 2021;(3):331-346
Abstract
Polyphosphates (polyP) are polymers of inorganic phosphates joined by high-energy bonds to form long chains. These chains are present in all forms of life but were once disregarded as 'molecular fossils'. PolyP has gained attention in recent years following new links to diverse biological roles ranging from energy storage to cell signaling. PolyP research in humans and other higher eukaryotes is limited by a lack of suitable tools and awaits the identification of enzymatic players that would enable more comprehensive studies. Therefore, many of the most important insights have come from single-cell model systems. Here, we review determinants of polyP metabolism, regulation, and function in major microbial systems, including bacteria, fungi, protozoa, and algae. We highlight key similarities and differences that may aid in our understanding of how polyP impacts cell physiology at a molecular level.
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Mechanistic Targets and Nutritionally Relevant Intervention Strategies to Break Obesity-Breast Cancer Links.
Bustamante-Marin, XM, Merlino, JL, Devericks, E, Carson, MS, Hursting, SD, Stewart, DA
Frontiers in endocrinology. 2021;:632284
Abstract
The worldwide prevalence of overweight and obesity has tripled since 1975. In the United States, the percentage of adults who are obese exceeds 42.5%. Individuals with obesity often display multiple metabolic perturbations, such as insulin resistance and persistent inflammation, which can suppress the immune system. These alterations in homeostatic mechanisms underlie the clinical parameters of metabolic syndrome, an established risk factor for many cancers, including breast cancer. Within the growth-promoting, proinflammatory milieu of the obese state, crosstalk between adipocytes, immune cells and breast epithelial cells occurs via obesity-associated hormones, angiogenic factors, cytokines, and other mediators that can enhance breast cancer risk and/or progression. This review synthesizes evidence on the biological mechanisms underlying obesity-breast cancer links, with emphasis on emerging mechanism-based interventions in the context of nutrition, using modifiable elements of diet alone or paired with physical activity, to reduce the burden of obesity on breast cancer.
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Sodium/glucose cotransporter 2 and renoprotection: From the perspective of energy regulation and water conservation.
Kitada, K, Kidoguchi, S, Nakano, D, Nishiyama, A
Journal of pharmacological sciences. 2021;(3):245-250
Abstract
Sodium/glucose cotransporter 2 (SGLT2) is a renal low-affinity high-capacity sodium/glucose cotransporter expressed in the apical membrane of the early segment of proximal tubules. SGLT2 reabsorbs filtered glucose in the kidney, and its inhibitors represent a new class of oral medications used for type 2 diabetes mellitus, which act by increasing glucose and sodium excretion in urine, thereby reducing blood glucose levels. However, clinical trials showed marked improvement of renal outcomes, even in nondiabetic kidney diseases, although the underlying mechanism of this renoprotective effect is unclear. We showed that long-term excretion of salt by the kidneys, which predisposes to osmotic diuresis and water loss, induces a systemic body response for water conservation. The energy-intensive nature of water conservation leads to a reprioritization of systemic body energy metabolism. According to current data, use of SGLT2 inhibitors may result in similar reprioritization of energy metabolism to prevent dehydration. In this review article, we discuss the beneficial effects of SGLT2 inhibition from the perspective of energy metabolism and water conservation.
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The Impact of Low Energy Availability on Nonexercise Activity Thermogenesis and Physical Activity Behavior in Recreationally Trained Adults.
Martin, A, Hofmann, H, Drenowatz, C, Wallmann-Sperlich, B, Sperlich, B, Koehler, K
International journal of sport nutrition and exercise metabolism. 2021;(4):329-336
Abstract
Energy availability describes the amount of dietary energy remaining for physiological functionality after the energy cost of exercise is deducted. The physiological and hormonal consequences of low energy availability (LEA) are well established, but the impact of LEA on physical activity behavior outside of exercise and, specifically, nonexercise activity thermogenesis (NEAT) has not been systematically examined. The authors conducted a secondary analysis of a repeated-measures crossover study in which recreationally trained young men (n = 6, 25 ± 1.0 years) underwent two 4-day conditions of LEA (15 kcal·kg fat-free mass-1 ·day-1) with and without endurance exercise (LEA + EX and LEA EX) and two energy-balanced control conditions (CON + EX and CON EX). The duration and intensity of physical activity outside of prescribed exercise were assessed using the SenseWear Pro3 armband. LEA did not alter NEAT (p = .41), nor time spent in moderate to vigorous (p = .20) and low-intensity physical activity (p = .17). However, time spent in low-intensity physical activity was lower in LEA + EX than LEA - EX (13.7 ± 0.3 vs. 15.2 ± 0.3 hr/day; p = .002). Short-term LEA does not seem to impact NEAT per se, but the way it is attained may impact physical activity behavior outside of exercise. As the participants expended similar amounts of energy during NEAT (900-1,300 kcal/day = 12.5-18.0 kcal·kg fat-free mass-1·day-1) and prescribed exercise bouts (15.0 kcal·kg fat-free mass-1·day-1), excluding it as a component of energy expenditure may skew the true energy available for physiological functionality in active populations.