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1.
Relative energy deficiency in sports (RED-S): elucidation of endocrine changes affecting the health of males and females.
Dipla, K, Kraemer, RR, Constantini, NW, Hackney, AC
Hormones (Athens, Greece). 2021;(1):35-47
Abstract
The purpose of this review is to present a different perspective of the relative energy deficiency syndrome, to improve understanding of associated endocrine alterations, and to highlight the need for further research in this area. The term "female athlete triad" was coined over 25 years ago to describe three interrelated components: disordered eating, menstrual dysfunction, and low bone mass. The syndrome's etiology is attributed to energy intake deficiency relative to energy expenditure required for health, function, and daily living. Recently, it became clear that there was a need to broaden the term, as the disorder is not an issue of only three interrelated problems but of a whole spectrum of insults resulting from low energy availability (LEA; i.e., insufficient energy availability to cover basic physiological demands) that can potentially affect any exerciser, irrespective of gender. The new model, termed relative energy deficiency in sport (RED-S), has received greater scrutiny in sports medicine due to its effects on both health and performance in athletes of both sexes. RED-S results from low-energy diets (intentional or unintentional) and/or excessive exercise. Energy deficiency reduces hypothalamic pulsatile release of gonadotropin-releasing hormone, this impairing anterior pituitary release of gonadotropins. In women, reduced FSH and LH pulsatility produces hypoestrogenism, causing functional hypothalamic amenorrhea and decreased bone mass. In men, it reduces testosterone and negatively affects bone health. Moreover, LEA alters other hormonal pathways, causing physiological consequences, such as alteration of the thyroid hormone signaling pathways, leptin levels, carbohydrate metabolism, the growth hormone/insulin-like growth factor-1 axis, and sympathetic/parasympathetic tone. This review explains and clarifies the effects of RED-S in both sexes.
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2.
Ovarian, breast, and metabolic changes induced by androgen treatment in transgender men.
Pirtea, P, Ayoubi, JM, Desmedt, S, T'Sjoen, G
Fertility and sterility. 2021;(4):936-942
Abstract
Gender-affirming hormone therapy (GAHT) is often provided to transgender people. In this review of the literature, the current knowledge of ovarian, breast, and metabolic changes (body composition, insulin resistance, bone density, cardiovascular risk factors such as lipids, blood pressure, and hematocrit) observed following GAHT in adult transgender men is discussed. A body of literature concurs to describe that long-term androgen therapy in transgender men exerts atrophic effects on the breast. There is currently no evidence of an increased risk of breast cancer. Long-term testosterone treatment induces ovarian effects that become visible after 6 months of therapy. These changes consist of both macroscopic and microscopic alterations of ovarian morphology that mimic the typical ovarian aspect encountered in women with polycystic ovary syndrome but without an effect on antral follicle count. Metabolic effects of long-term androgen treatment in transgender men put them at par with cisgender men in terms of lipid profile, insulin resistance, and overall mortality. Body composition changes as desired after testosterone administration in most transgender men, and insulin resistance decreases with virilization. There are no detrimental effects on bone mineral density. Cardiometabolic risk and morbidity data are currently reassuring, even if certain studies show conflicting results. An increase in blood pressure and a decrease in high-density lipoprotein cholesterol have been reported as risk factors, whereas polycythemia is rare and treatable. Most available data are observational and based on biochemical markers instead of the more direct measures of cardiovascular damage. An explanation for these observed changes is mostly lacking. Psychological stress and lifestyle factors are often forgotten in a much needed integrated approach.
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3.
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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4.
Energy Expenditure Improved Risk Factors Associated with Renal Function Loss in NAFLD and MetS Patients.
Abbate, M, Mascaró, CM, Montemayor, S, Barbería-Latasa, M, Casares, M, Gómez, C, Angullo-Martinez, E, Tejada, S, Abete, I, Zulet, MA, et al
Nutrients. 2021;(2)
Abstract
To assess the efficacy of three lifestyle interventions on the reduction of liver fat content and metabolic syndrome (MetS), and whether such reductions would influence renal outcomes, we conducted a randomized controlled trial on 128 participants with MetS and non-alcoholic fatty liver disease (NAFLD), as well as available data on estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatine ratio (UACR). Patients were randomized in 1:1:1 ratio to either Conventional Diet, Mediterranean diet (MD)-high meal frequency, and MD-physical activity groups. Each intervention aimed at reducing caloric intake by 25%-30% of baseline intake and increase energy expenditure by 400 kcal/70 kg. Patients attended regular visits and were followed-up for 6 months. Increased albuminuria was present in 13.3% of patients, while 32.8% showed hyperfiltration. UACR reduction was associated with higher levels of UACR at baseline but not with changes in liver fat. eGFR decreased in patients presenting hyperfiltration at baseline and was associated with reduction in liver fat and insulin resistance, as well as with increase in energy expenditure (R2 = 0.248, p = 0.006). No significant differences were observed between the three treatment groups. In patients with NAFLD and MetS, energy expenditure significantly reduced hepatic fat accumulation and insulin resistance, which reduced glomerular hyperfiltration. Increased albuminuria was reduced, but it was not associated with reduced liver fat.
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5.
Effects of oral administration of common antioxidant supplements on the energy metabolism of red blood cells. Attenuation of oxidative stress-induced changes in Rett syndrome erythrocytes by CoQ10.
Di Pierro, D, Ciaccio, C, Sbardella, D, Tundo, GR, Bernardini, R, Curatolo, P, Galasso, C, Pironi, V, Coletta, M, Marini, S
Molecular and cellular biochemistry. 2020;(1-2):101-113
Abstract
Nutritional supplements are traditionally employed for overall health and for managing some health conditions, although controversies are found concerning the role of antioxidants-mediated benefits in vivo. Consistently with its critical role in systemic redox buffering, red blood cell (RBC) is recognized as a biologically relevant target to investigate the effects of oxidative stress. In RBC, reduction of the ATP levels and adenylate energy charge brings to disturbance in intracellular redox status. In the present work, several popular antioxidant supplements were orally administrated to healthy adults and examined for their ability to induce changes on the energy metabolism and oxidative status in RBC. Fifteen volunteers (3 per group) were treated for 30 days per os with epigallocatechin gallate (EGCG) (1 g green tea extract containing 50% EGCG), resveratrol (325 mg), coenzyme Q10 (CoQ10) (300 mg), vitamin C (1 g), and vitamin E (400 U.I.). Changes in the cellular levels of high-energy compounds (i.e., ATP and its catabolites, NAD and GTP), GSH, GSSG, and malondialdehyde (MDA) were simultaneously analyzed by ion-pairing HPLC. Response to oxidative stress was further investigated through the oxygen radical absorptive capacity (ORAC) assay. According to our experimental approach, (i) CoQ10 appeared to be the most effective antioxidant inducing a high increase in ATP/ADP, ATP/AMP, GSH/GSSG ratio and ORAC value and, in turn, a reduction of NAD concentration, (ii) EGCG modestly modulated the intracellular energy charge potential, while (iii) Vitamin E, vitamin C, and resveratrol exhibited very weak effects. Given that, the antioxidant potential of CoQ10 was additionally assessed in a pilot study which considered individuals suffering from Rett syndrome (RTT), a severe X-linked neuro-developmental disorder in which RBC oxidative damages provide biological markers for redox imbalance and chronic hypoxemia. RTT patients (n = 11), with the typical clinical form, were supplemented for 12 months with CoQ10 (300 mg, once daily). Level of lipid peroxidation (MDA production) and energy state of RBCs were analyzed at 2 and 12 months. Our data suggest that CoQ10 may significantly attenuate the oxidative stress-induced damage in RTT erythrocytes.
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6.
Metabolic and Cardiovascular Effects of Switching Thiazides to Amlodipine in Hypertensive Patients With and Without Type 2 Diabetes (the Diuretics and Diabetes Control Study).
Buscemi, S, Buscemi, C, Borzì, AM, Cosentino, L, Rosafio, G, Randazzo, C, Colomba, D, Di Raimondo, D, Pluchinotta, FR, Parrinello, G
Metabolic syndrome and related disorders. 2020;(2):110-118
Abstract
Background: Different studies have indicated that thiazide diuretics can increase the risk of developing type 2 diabetes (T2D). Therefore, in this study, we investigated whether switching from hydrochlorothiazide (HCTZ) to amlodipine resulted in ameliorating different cardiovascular and metabolic measures in hypertensive patients with or without T2D. Methods: This study [Diuretics and Diabetes Control (DiaDiC)] was a 6-week, single-blind, single-center randomized controlled trial. The first 20 normal glucose-tolerant, 20 prediabetic, and 20 T2D consecutive patients were randomized to continue the previous antihypertensive treatment with HCTZ (12.5-25 mg/day) or to switch from HCTZ to amlodipine (2.5-10 mg/day). The primary endpoints were the absolute change in 7-day continuous subcutaneous glucose monitoring (CSGM) glycemia, serum uric acid concentrations, and endothelial function [measured as flow-mediated dilation (FMD)]. Other secondary endpoints were investigated, including changes in glycated hemoglobin (HbA1c), glycemic variability from 7-day CSGM, and the estimated glomerular filtration rate (eGFR). Results: Amlodipine treatment was associated with a significant reduction in HbA1c (P = 0.03) for both 7-day CSGM glycemia (P = 0.01) and glycemic variability (coefficient of variability %: HCTZ +3%, amlodipine -2.8%), and a reduction in uric acid concentrations (P < 0.001), especially in participants with T2D or prediabetes. Following amlodipine treatment, a significant increase in both eGFR (P = 0.01) and FMD (P = 0.02) was also observed. Conclusions: This study demonstrates that the replacement of HCTZ with amlodipine has several metabolic and cardiovascular beneficial effects. However, further intervention studies are necessary to confirm the clinical effects of thiazides, especially in diabetic people and in those at risk of diabetes.
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7.
Dietary anti-inflammatory index, metabolic syndrome and transition in metabolic status; a gender-specific analysis of ATTICA prospective study.
Kouvari, M, Panagiotakos, DB, Naumovski, N, Chrysohoou, C, Georgousopoulou, EN, Yannakoulia, M, Tousoulis, D, Pitsavos, C, ,
Diabetes research and clinical practice. 2020;:108031
Abstract
AIMS: To examine the association between dietary anti-inflammatory index (D-AII) and metabolic syndrome (MetS)prevalence, 10-year (2002-2012) diabetes, hypertension, hypercholesterolaemia incidence and 10-year transition from healthy (absence of all MetS traits, excluding waist circumference) to unhealthy metabolic status. METHODS In 2001-2002, n = 1514 men and n = 1528 women (>18 years old) in Athens, Greece, free of cardiovascular disease were recruited. MetS was defined according to the revised NCEP ATP III (2005) or the IDF criteria or the harmonized criteria. The validated D-AII was calculated using a standardized procedure (range 10-77). RESULTS Inverse associations were observed between D-AII and transition from healthy to unhealthy metabolic status (Odds Ratio (OR)3rd vs. 1st tertile = 0.88 95% Confidence Interval (95%CI)(0.73, 0.98)) and diabetes (OR3rd vs. 1st tertile = 0.55, 95%CI(0.29, 0.77)). In women, D-AII was inversely associated with transition from healthy to unhealthy metabolic status (OR3rd vs. 1st tertile = 0.55, 95%CI(0.26, 0.90), diabetes (OR3rd vs. 1st tertile = 0.41, 95%CI(0.18, 0.64) and hypertension (OR3rd vs. 1st tertile = 0.75, 95%CI(0.20, 0.95), yet only with diabetes incidence in men (OR3rd vs. 1st tertile = 0.62, 95%CI(0.38, 0.93). CONCLUSIONS Diet with high anti-inflammatory load seems an effective preventive measure to retain a metabolically benign status, principally in terms of glycemic control.
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8.
Effects of preeclampsia and eclampsia on maternal metabolic and biochemical outcomes in later life: a systematic review and meta-analysis.
Alonso-Ventura, V, Li, Y, Pasupuleti, V, Roman, YM, Hernandez, AV, Pérez-López, FR
Metabolism: clinical and experimental. 2020;:154012
Abstract
OBJECTIVE To evaluate the association between preeclampsia (PE) and eclampsia (E) on subsequent metabolic and biochemical outcomes. METHODS Systematic review and meta-analysis of observational studies. We searched five engines until November 2018 for studies evaluating the effects of PE/E on metabolic and biochemical outcomes after delivery. PE was defined as presence of hypertension and proteinuria at >20 weeks of pregnancy; controls did not have PE/E. Primary outcomes were blood pressure (BP), body mass index (BMI), metabolic syndrome (MetS), blood lipids and glucose levels. Random effects models were used for meta-analyses, and effects reported as risk difference (RD) or mean difference (MD) and their 95% confidence interval (CI). Subgroup analyses by time of follow up, publication year, and confounder adjustment were performed. RESULTS We evaluated 41 cohorts including 3300 PE/E and 13,967 normotensive controls. Women were followed up from 3 months after delivery up to 32 years postpartum. In comparison to controls, PE/E significantly increased systolic BP (MD = 8.3 mmHg, 95%CI 6.8 to 9.7), diastolic BP (MD = 6.8 mmHg, 95%CI 5.6 to 8.0), BMI (MD = 2.0 kg/m2; 95%CI 1.6 to 2.4), waist (MD = 4.3 cm, 95%CI 3.1 to 5.5), waist-to-hip ratio (MD = 0.02, 95%CI 0.01 to 0.03), weight (MD = 5.1 kg, 95%CI 2.2 to 7.9), total cholesterol (MD = 4.6 mg/dL, CI 1.5 to 7.7), LDL (MD = 4.6 mg/dL; 95%CI 0.2 to 8.9), triglycerides (MD = 7.7 mg/dL, 95%CI 3.6 to 11.7), glucose (MD = 2.6 mg/dL, 95%CI 1.2 to 4.0), insulin (MD = 19.1 pmol/L, 95%CI 11.9 to 26.2), HOMA-IR index (MD = 0.7, 95%CI 0.2 to 1.2), C reactive protein (MD = 0.05 mg/dL, 95%CI 0.01 to 0.09), and the risks of hypertension (RD = 0.24, 95%CI 0.15 to 0.33) and MetS (RD = 0.11, 95%CI 0.08 to 0.15). Also, PE/E reduced HDL levels (MD = -2.15 mg/dL, 95%CI -3.46 to -0.85). Heterogeneity of effects was high for most outcomes. Risk of bias was moderate across studies. Subgroup analyses showed similar effects as main analyses. CONCLUSION Women who had PE/E have worse metabolic and biochemical profile than those without PE/E in an intermediate to long term follow up period.
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9.
Molecular Mechanisms Linking Nutrition to Metabolic Homeostasis: An Overview Picture of Current Understanding.
Pignatti, C, D'Adamo, S, Flamigni, F, Cetrulllo, S
Critical reviews in eukaryotic gene expression. 2020;(6):543-564
Abstract
Increasing evidence supports the notion that in humans many pathological conditions including obesity, metabolic syndrome, and type 2 diabetes are closely related to the amount and quality of each nutritional component and to an impairment of the metabolic homeostatic mechanisms of their utilization. Cell signaling pathways that sense the availability of nutrients and the energy status of the cells communicate with signaling pahways triggered by hormones and growth factors to coordinately regulate whole-body metabolic homeostasis. The aim of this review is to provide an overview picture of current knowledge about the main molecular mechanisms that connect nutritional status, hormones, and nutrient levels with gene expression, metabolic homeostasis, and nutrient sensing. We recapitulate molecular mechanisms governing fuel selection between glucose and fatty acids in different nutritional conditions, highlighting metabolic flexibility as mechanism to ensure metabolic health. Disrupted metabolic flexibility, or metabolic inflexibility, is associated with many pathological conditions including metabolic syndrome, type 2 diabetes mellitus, and cancer. We also describe how macronutrients that can be used as energy sources may reciprocally modulate their own metabolism as well as directly interact with transcriptional factors, nutrient sensors and nutrient sensing pathways in order to achieve metabolic homeostasis.
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10.
Ghrelin forms in the modulation of energy balance and metabolism.
Gortan Cappellari, G, Barazzoni, R
Eating and weight disorders : EWD. 2019;(6):997-1013
Abstract
Ghrelin is a gastric hormone circulating in acylated (AG) and unacylated (UnAG) forms. This narrative review aims at presenting current emerging knowledge on the impact of ghrelin forms on energy balance and metabolism. AG represents ~ 10% of total plasma ghrelin, has an appetite-stimulating effect and is the only form for which a receptor has been identified. Moreover, other metabolic AG-induced effects have been reported, including the modulation of glucose homeostasis with stimulation of liver gluconeogenesis, the increase of fat mass and the improvement of skeletal muscle mitochondrial function. On the other hand, UnAG has no orexigenic effects, however recent reports have shown that it is directly involved in the modulation of skeletal muscle energy metabolism by improving a cluster of interlinked functions including mitochondrial redox activities, tissue inflammation and insulin signalling and action. These findings are in agreement with human studies which show that UnAG circulating levels are positively associated with insulin sensitivity both in metabolic syndrome patients and in a large cohort from the general population. Moreover, ghrelin acylation is regulated by a nutrient sensor mechanism, specifically set on fatty acids availability. These recent findings consistently point towards a novel independent role of UnAG as a regulator of muscle metabolic pathways maintaining energy status and tissue anabolism. While a specific receptor for UnAG still needs to be identified, recent evidence strongly supports the hypothesis that the modulation of ghrelin-related molecular pathways, including those involved in its acylation, may be a potential novel target in the treatment of metabolic derangements in disease states characterized by metabolic and nutritional complications.Level of evidence Level V, narrative review.