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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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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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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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Is Weight Loss More Severe in Older People with Dementia?
Tjahyo, AS, Gandy, J, Porter, J, Henry, CJ
Journal of Alzheimer's disease : JAD. 2021;(1):57-73
Abstract
Weight loss, a hallmark feature of dementia, is associated with higher mortality in older people. However, there is a lack of consensus in the literature as to whether the weight loss commonly observed in older people with dementia results from reduced energy intake and/or increased energy expenditure. Understanding the cause of energy imbalance in older people with dementia would allow more targeted interventions to avoid detrimental health effects in this vulnerable group. In this paper, we review studies that have considered weight change, energy intake, and energy expenditure in older people with and without dementia. We critically assess the studies' methodology and outline the various factors which may decrease and increase energy intake and expenditure respectively in older people with and without dementia. Current available literature does not support the view that there is a lower energy intake and/or a higher energy expenditure in older people with dementia when compared to those without dementia. The need for more high-quality studies is also highlighted in order to shed more light towards this issue which continues to elude researchers and clinicians alike.
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Direct or indirect regulation of muscle protein synthesis by energy status?
Moinard, C, Fontaine, E
Clinical nutrition (Edinburgh, Scotland). 2021;(4):1893-1896
Abstract
Muscle protein synthesis (MPS) is a complex and finely-regulated mechanism that plays a key role in muscle homeostasis. Amino acid bioavailability is widely considered a major driver of MPS regulation via mTOR pathway activation. However, recent results suggest that amino acid bioavailability affects cellular energy status. Whatever the tool used to modulate energy status (amino acid depletion or mild mitochondrial uncoupling), a decrease in cellular energy status decreases MPS, without necessarily involving the mTOR pathway. Here we propose that energy status directly regulates one or several energy-consuming step(s) during MPS. This new paradigm modifies our vision of protein metabolism and raises prospects for new advances in therapeutics.
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Pyrophosphate as an alternative energy currency in plants.
Igamberdiev, AU, Kleczkowski, LA
The Biochemical journal. 2021;(8):1515-1524
Abstract
In the conditions of [Mg2+] elevation that occur, in particular, under low oxygen stress and are the consequence of the decrease in [ATP] and increase in [ADP] and [AMP], pyrophosphate (PPi) can function as an alternative energy currency in plant cells. In addition to its production by various metabolic pathways, PPi can be synthesized in the combined reactions of pyruvate, phosphate dikinase (PPDK) and pyruvate kinase (PK) by so-called PK/PPDK substrate cycle, and in the reverse reaction of membrane-bound H+-pyrophosphatase, which uses the energy of electrochemical gradients generated on tonoplast and plasma membrane. The PPi can then be consumed in its active forms of MgPPi and Mg2PPi by PPi-utilizing enzymes, which require an elevated [Mg2+]. This ensures a continuous operation of glycolysis in the conditions of suppressed ATP synthesis, keeping metabolism energy efficient and less dependent on ATP.
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Mechanism of Action of Acupuncture in Obesity: A Perspective From the Hypothalamus.
Wang, L, Yu, CC, Li, J, Tian, Q, Du, YJ
Frontiers in endocrinology. 2021;:632324
Abstract
Obesity is a prevalent metabolic disease caused by an imbalance in food intake and energy expenditure. Although acupuncture is widely used in the treatment of obesity in a clinical setting, its mechanism has not been adequately elucidated. As the key pivot of appetite signals, the hypothalamus receives afferent and efferent signals from the brainstem and peripheral tissue, leading to the formation of a complex appetite regulation circuit, thereby effectively regulating food intake and energy homeostasis. This review mainly discusses the relationship between the hypothalamic nuclei, related neuropeptides, brainstem, peripheral signals, and obesity, as well as mechanisms of acupuncture on obesity from the perspective of the hypothalamus, exploring the current evidence and therapeutic targets for mechanism of action of acupuncture in obesity.
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Flavins in the electron bifurcation process.
Kayastha, K, Vitt, S, Buckel, W, Ermler, U
Archives of biochemistry and biophysics. 2021;:108796
Abstract
The discovery of a new energy-coupling mechanism termed flavin-based electron bifurcation (FBEB) in 2008 revealed a novel field of application for flavins in biology. The key component is the bifurcating flavin endowed with strongly inverted one-electron reduction potentials (FAD/FAD•- ≪ FAD•-/FADH-) that cooperatively transfers in its reduced state one low and one high-energy electron into different directions and thereby drives an endergonic with an exergonic reduction reaction. As energy splitting at the bifurcating flavin apparently implicates one-electron chemistry, the FBEB machinery has to incorporate prior to and behind the central bifurcating flavin 2e-to-1e and 1e-to-2e switches, frequently also flavins, for oxidizing variable medium-potential two-electron donating substrates and for reducing high-potential two-electron accepting substrates. The one-electron carriers ferredoxin or flavodoxin serve as low-potential (high-energy) electron acceptors, which power endergonic processes almost exclusively in obligate anaerobic microorganisms to increase the efficiency of their energy metabolism. In this review, we outline the global organization of FBEB enzymes, the functions of the flavins therein and the surrounding of the isoalloxazine rings by which their reduction potentials are specifically adjusted in a finely tuned energy landscape.
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Post-exercise recovery for the endurance athlete with type 1 diabetes: a consensus statement.
Scott, SN, Fontana, FY, Cocks, M, Morton, JP, Jeukendrup, A, Dragulin, R, Wojtaszewski, JFP, Jensen, J, Castol, R, Riddell, MC, et al
The lancet. Diabetes & endocrinology. 2021;(5):304-317
Abstract
There has been substantial progress in the knowledge of exercise and type 1 diabetes, with the development of guidelines for optimal glucose management. In addition, an increasing number of people living with type 1 diabetes are pushing their physical limits to compete at the highest level of sport. However, the post-exercise recovery routine, particularly with a focus on sporting performance, has received little attention within the scientific literature, with most of the focus being placed on insulin or nutritional adaptations to manage glycaemia before and during the exercise bout. The post-exercise recovery period presents an opportunity for maximising training adaption and recovery, and the clinical management of glycaemia through the rest of the day and overnight. The absence of clear guidance for the post-exercise period means that people with type 1 diabetes should either develop their own recovery strategies on the basis of individual trial and error, or adhere to guidelines that have been developed for people without diabetes. This Review provides an up-to-date consensus on post-exercise recovery and glucose management for individuals living with type 1 diabetes. We aim to: (1) outline the principles and time course of post-exercise recovery, highlighting the implications and challenges for endurance athletes living with type 1 diabetes; (2) provide an overview of potential strategies for post-exercise recovery that could be used by athletes with type 1 diabetes to optimise recovery and adaptation, alongside improved glycaemic monitoring and management; and (3) highlight the potential for technology to ease the burden of managing glycaemia in the post-exercise recovery period.
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Electron transfer flavoprotein and its role in mitochondrial energy metabolism in health and disease.
Henriques, BJ, Katrine Jentoft Olsen, R, Gomes, CM, Bross, P
Gene. 2021;:145407
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Abstract
Electron transfer flavoprotein (ETF) is an enzyme with orthologs from bacteria to humans. Human ETF is nuclear encoded by two separate genes, ETFA and ETFB, respectively. After translation, the two subunits are imported to the mitochondrial matrix space and assemble into a heterodimer containing one FAD and one AMP as cofactors. ETF functions as a hub taking up electrons from at least 14 flavoenzymes, feeding them into the respiratory chain. This represents a major source of reducing power for the electron transport chain from fatty acid oxidation and amino acid degradation. Transfer of electrons from the donor enzymes to ETF occurs by direct transfer between the enzyme bound flavins, a process that is tightly regulated by the polypeptide chain and by protein:protein interactions. ETF, in turn relays electrons to the iron sulfur cluster of the inner membrane protein ETF:QO, from where they travel via the FAD in ETF:QO to ubiquinone, entering the respiratory chain at the level of complex III. ETF recognizes its dehydrogenase partners via a recognition loop that anchors the protein on its partner followed by dynamic movements of the ETF flavin domain that bring redox cofactors in close proximity, thus promoting electron transfer. Genetic mutations in the ETFA or ETFB genes cause the Mendelian disorder multiple acyl-CoA dehydrogenase deficiency (MADD; OMIM #231680). We here review the knowledge on human ETF and investigations of the effects of disease-associated missense mutations in this protein that have promoted the understanding of the essential role that ETF plays in cellular metabolism and human disease.