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1.
The Type 2 Deiodinase Thr92Ala Polymorphism Is Associated with Higher Body Mass Index and Fasting Glucose Levels: A Systematic Review and Meta-Analysis.
Wang, X, Chen, K, Zhang, C, Wang, H, Li, J, Wang, C, Teng, W, Shan, Z, Lai, Y
BioMed research international. 2021;:9914009
Abstract
BACKGROUND Type 2 deiodinase (Dio2) is a selenoenzyme that is mainly expressed in the endoplasmic reticulum of the central nervous system, brown adipose tissue, and placenta and is responsible for outer ring deiodination of thyroxine (T4) to form biologically active triiodothyronine (T3). The Thr92Ala polymorphism of Dio2 has been found to be a potential risk factor for various diseases beyond the hypothalamus-pituitary-thyroid (HPT) axis. METHODS We searched the relevant studies in the PubMed, Embase, and Cochrane Library databases and Google Scholar. A systematic review and meta-analysis of studies on the Thr92Ala polymorphism and metabolic parameters beyond the HPT axis (e.g., BMI, fasting glycemic traits, plasma lipid levels, and hypertension risk) were performed. RESULTS Six eligible studies that analyzed the relationship between the Thr92Ala polymorphism and metabolic parameters beyond the thyroid were identified. All selected studies excluded patients with thyroid dysfunction, and diabetic patients were also excluded when fasting glucose and fasting insulin levels were meta-analyzed. The Thr92Ala polymorphism was found to be a significant risk factor for higher BMI (Std. mean difference 0.31 (0.01, 0.60), p = 0.04) and higher fasting glucose levels (Std. mean difference 1.18 (0.05, 2.31), p = 0.04). However, fasting insulin levels, plasma lipid levels, and hypertension risk showed a nonsignificant association with the Thr92Ala polymorphism. CONCLUSION Compared with euthyroid noncarriers (Thr/Thr), euthyroid Ala92-Dio2 carriers showed increased BMI levels, and Ala92-Dio2 carriers also had higher fasting plasma glucose levels than matched euthyroid nondiabetic noncarriers.
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2.
Five Days Periodic Fasting Elevates Levels of Longevity Related Christensenella and Sirtuin Expression in Humans.
Lilja, S, Stoll, C, Krammer, U, Hippe, B, Duszka, K, Debebe, T, Höfinger, I, König, J, Pointner, A, Haslberger, A
International journal of molecular sciences. 2021;(5)
Abstract
Periodic fasting (PF) is an increasingly popular approach that assists in the management of metabolic and inflammatory diseases as well as in preventing mechanisms involved in aging. However, little is known about the effects of fasting on gut microbiota and its impact on the epigenetic regulation of metabolically relevant enzymes, especially sirtuins (SIRTs). We analyzed the effect of periodic fasting on the human gut microbiota, SIRTs expression, and mitochondrial content in 51 males and females. The participants fasted under supervision for five consecutive days following the Buchinger fasting guidelines. Ketogenesis, selected mRNAs, miRNAs, mitochondrial (mt) DNA, and gut composition were analyzed before and after PF. PF triggered a significant switch in metabolism, as indicated by the increase in ß-hydroxybutyrate (BHB) and pyruvate dehydrogenase kinase isoform 4 (PDK4) expression in the capillary blood. MtDNA, SIRT1, SIRT3, and miRlet7b-5p expression in blood cells were elevated, whereas SIRT6 and miR125b-5p were not affected. Following fasting, gut microbiota diversity increased, and a statistically significant correlation between SIRT1 gene expression and the abundance of Prevotella and Lactobacillus was detected. The abundance of longevity related Christensenella species increased after fasting and inversely correlated with age as well as body mass index (BMI). Thus, this represents the first study that showing that fasting not only changes the composition of the gut microbiota, making it more diverse, but also affects SIRT expression in humans.
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3.
Evaluating Solubility of Celecoxib in Age-Appropriate Fasted- and Fed-State Gastric and Intestinal Biorelevant Media Representative of Adult and Pediatric Patients: Implications on Future Pediatric Biopharmaceutical Classification System.
Shawahna, R, Zyoud, A, Haj-Yahia, A, Taya, R
AAPS PharmSciTech. 2021;(3):84
Abstract
Prediction of performance of traditional, reformulated, and novel oral formulations in adults and pediatrics is of great importance. This study was conducted to assess solubility of celecoxib in age-appropriate fasted- and fed-state gastric and intestinal biorelevant media, classify celecoxib into biopharmaceutical classification system (BCS), and assess the effects of age-related developmental changes in the composition and volume of gastrointestinal fluids on the solubility and performance of oral formulations containing celecoxib. Solubility of celecoxib was assessed at 37°C in the pH range specified by the BCS-based criteria in 13 age-appropriate biorelevant media reflective of the gastric and proximal small intestinal environment in both fasted and fed states in adults and different pediatric subpopulations. A validated HPLC-UV method was used to quantify celecoxib. Experimental and computational molecular descriptors and in vivo pharmacokinetic data were used to assign the permeability class of celecoxib. Celecoxib belonged to BCS class 2. The pediatric to adult solubility ratios were outside the 80-125% boundaries in 3 and borderline in 1 biorelevant media. Significant age-related variability could be predicted for oral formulations containing celecoxib intended for pediatric use. Findings of this study indicated that the criteria used in the adult BCS might not be directly applied to pediatric subpopulations.
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4.
Impact of prolonged fasting on insulin secretion, insulin action, and hepatic versus whole body insulin secretion disposition indices in healthy young males.
Jørgensen, SW, Hjort, L, Gillberg, L, Justesen, L, Madsbad, S, Brøns, C, Vaag, AA
American journal of physiology. Endocrinology and metabolism. 2021;(2):E281-E290
Abstract
The extent to which reduced insulin secretion during prolonged fasting reflects failure to compensate for whole body insulin resistance or a normal adjustment to potentially increased hepatic insulin action is unknown. We examined the effects of 36- versus 12-h fasting on insulin secretion and whole body versus hepatic insulin action in 13 healthy young males. Hepatic glucose production and insulin action were studied using stable isotopes, whereas whole body insulin action and insulin secretion were studied using an intravenous glucose tolerance test (IVGTT) and minimal modeling. Insulin, glucose, and lipid profiles were subsequently measured during a refeeding meal test. Prolonged fasting caused a minor reduction of first-phase insulin secretion in a context of improved hepatic insulin action, contrasting an increase in whole body insulin resistance. Accordingly, prolonged fasting was associated with opposite-directed effects on hepatic versus whole body insulin secretion disposition indices. Thirty-six-hour fasting compared with 12-h fasting was associated with increased serum insulin levels during the refeeding meal test. In conclusion, reduced insulin secretion during prolonged fasting may represent a healthy response to improved hepatic insulin action. Use of insulin secretion disposition indices without taking organ-specific insulin action into account may lead to erroneous conclusions.NEW & NOTEWORTHY Thirty-six-hour prolonged, compared with 12-h overnight fasting, is associated with slightly reduced first-phase insulin secretion in the face of opposite-directed changes in hepatic versus whole body insulin action in healthy young males. The paradoxical finding of increased hepatic versus decreased whole body insulin secretion disposition indices during prolonged fasting challenges the physiological understanding and validity of insulin secretion disposition indices not taking organ-specific insulin action into account.
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5.
Characterization of endogenous bile acid composition in individuals with cold-activated brown adipose tissue.
Herz, CT, Kulterer, OC, Prager, M, Langer, FB, Prager, G, Marculescu, R, Fauler, G, Hacker, M, Kautzky-Willer, A, Trauner, M, et al
Molecular and cellular endocrinology. 2021;:111403
Abstract
INTRODUCTION Bile acid signaling has been suggested to promote BAT activity in various experimental models. However, little is known if and how physiologic bile acid metabolism is linked to BAT function in humans. Here we investigated the association between BAT activity and circulating bile acid concentrations in lean and obese individuals. METHODS BAT 18F-fluorodeoxyglucose uptake was measured after a standardized cooling protocol by positron emission tomography/computed tomography. Cold-induced thermogenesis was assessed by indirect calorimetry. Fasting bile acid concentrations were determined by high performance liquid chromatography-high-resolution mass spectrometry. RESULTS In a cohort of 24 BAT-negative and 20 BAT-positive individuals matched by age, sex, and body mass index, circulating bile acid levels were similar between groups except for higher ursodeoxycholic acid and a trend towards a lower 12α-OH/non-12α-OH bile acid ratio in lean participants with active BAT compared to those without. Moreover, the 12α-OH/non-12α-OH ratio, a marker of CYP8B1 activity, correlated negatively with BAT volume and activity. CONCLUSION Fasting concentrations of major bile acids are not associated with cold-induced BAT activity in humans. However, the inverse association between BAT activity and 12α-OH/non-12α-OH ratio may suggest CYP8B1 as a potential new target in BAT function and warrants additional investigation.
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6.
A Low-Calorie Diet with or without Exercise Reduces Postprandial Aortic Waveform in Females with Obesity.
Heiston, EM, Gilbertson, NM, Eichner, NZM, Malin, SK
Medicine and science in sports and exercise. 2021;(4):796-803
Abstract
PURPOSE Arterial stiffness is considered a predictor of cardiovascular disease. Females have higher values of arterial stiffness than males, suggesting a greater risk of heart-related complications. Although a low-calorie diet (LCD) reduces fasting arterial stiffness, in part through weight loss, it is unknown if interval exercise (INT) adds to the benefit of LCD on fasting and postprandial arterial stiffness in females with obesity. METHODS Twenty-five females (47 ± 2.6 yr, 37.6 ± 1.3 kg·m-2) were randomized to 13 d of LCD (n = 12; mixed meals of ~1200 kcal·d-1) or LCD + INT (n = 13; 60 min·d-1 of supervised 3-min intervals at 90% HRpeak and 50% HRpeak). Arterial stiffness (augmentation index [AIx] and carotid-femoral pulse wave velocity [cfPWV]) and blood biochemistries were measured during a 75-g oral glucose tolerance test before and after the intervention to determine fasting and postprandial arterial stiffness as well as insulin sensitivity (simple index of insulin sensitivity [SIIS]) and inflammation (C-reactive protein, interleukin 8, and tumor necrosis factor alpha). RESULTS Although LCD + INT increased V˙O2peak and HDL compared with LCD (P = 0.04 and P < 0.01, respectively), both interventions decreased body fat, LDL, total cholesterol, and triglycerides (all P < 0.01) and increased SIIS (P = 0.03). Despite no effect on fasting AIx (P = 0.27), LCD and LCD + INT decreased AIx60min (-7.4% ± 4.3% vs -7.0% ± 5.0%, P = 0.04) and tAUC120min (-663 ± 263 vs -457 ± 406, P = 0.03). There were no changes in fasting cfPWV (P = 0.91) or cfPWV120min (P = 0.62). Increased SIIS and decreased interleukin 8 were associated with reduced fasting AIx (r = -0.44, P = 0.03, and r = 0.40, P = 0.055), whereas decreased C-reactive protein correlated with reduced postprandial AIx60min (r = 0.43, P = 0.04). CONCLUSION Independent of exercise, 13 d of LCD reduces postprandial AIx in females with obesity. Insulin sensitivity and inflammation correlated with improved arterial stiffness, suggesting unique mechanisms regulate fasted versus postprandial arterial stiffness.
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7.
Fasting and Exercise Induce Changes in Serum Vitamin D Metabolites in Healthy Men.
Żychowska, M, Rola, R, Borkowska, A, Tomczyk, M, Kortas, J, Anczykowska, K, Pilis, K, Kowalski, K, Pilch, W, Antosiewicz, J
Nutrients. 2021;(6)
Abstract
BACKGROUND Vitamin D plays pleiotropic roles in the body and hence, changes in its metabolism and distribution during starvation could play an important role in the adaptive response to famine. We aimed to identify the responses of some vitamin D metabolites to 8 d of fasting and exercise. METHODS A repeated-measures design was implemented, in which 14 male volunteers fasted for 8 d and performed an exercise test before and after fasting. Serum samples were collected on day 1 after night fasting and after 8 d of complete food restriction, before and 1 h and 3 h after exercise. RESULTS After 8 d of fasting, compared with baseline values, serum 24,25(OH)2D3 and 3-epi-25(OH)D3 levels significantly increased; those of 25(OH)D3 and 1,25(OH)2D3 were unaffected; and those of 25(OH)D2 decreased. Exercise on the first day of fasting induced an increase in serum 3-epi-25(OH)D3 levels, while exercise performed after 8 d of fasting induced an increase in 25(OH)D3, 24,25(OH)2D3, 25(OH)D2, and 3-epi-25(OH)D3 levels. CONCLUSION Increases in 24,25(OH)2D3 and 3-epi-25(OH)D3 levels imply that fasting stimulates vitamin D metabolism. The effects of exercise on serum vitamin D metabolites, which are most pronounced after fasting and in subjects with serum 25(OH)D3 above 25 ng/mL, support the notion that fasting and exercise augment vitamin D metabolism.
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8.
Divergent serum metabolomic, skeletal muscle signaling, transcriptomic, and performance adaptations to fasted versus whey protein-fed sprint interval training.
Aird, TP, Farquharson, AJ, Bermingham, KM, O'Sulllivan, A, Drew, JE, Carson, BP
American journal of physiology. Endocrinology and metabolism. 2021;(6):E802-E820
Abstract
Sprint interval training (SIT) is a time-efficient alternative to endurance exercise, conferring beneficial skeletal muscle metabolic adaptations. Current literature has investigated the nutritional regulation of acute and chronic exercise-induced metabolic adaptations in muscle following endurance exercise, principally comparing the impact of training in fasted and carbohydrate-fed (CHO) conditions. Alternative strategies such as exercising in low CHO, protein-fed conditions remain poorly characterized, specifically pertaining to adaptations associated with SIT. Thus, this study aimed to compare the metabolic and performance adaptations to acute and short-term SIT in the fasted state with preexercise hydrolyzed (WPH) or concentrated (WPC) whey protein supplementation. In healthy males, preexercise protein ingestion did not alter exercise-induced increases in PGC-1α, PDK4, SIRT1, and PPAR-δ mRNA expression following acute SIT. However, supplementation of WPH beneficially altered acute exercise-induced CD36 mRNA expression. Preexercise protein ingestion attenuated acute exercise-induced increases in muscle pan-acetylation and PARP1 protein content compared with fasted SIT. Acute serum metabolomic differences confirmed greater preexercise amino acid delivery in protein-fed compared with fasted conditions. Following 3 wk of SIT, training-induced increases in mitochondrial enzymatic activity and exercise performance were similar across nutritional groups. Interestingly, resting muscle acetylation status was downregulated in WPH conditions following training. Such findings suggest preexercise WPC and WPH ingestion positively influences metabolic adaptations to SIT compared with fasted training, resulting in either similar or enhanced performance adaptations. Future studies investigating nutritional modulation of metabolic adaptations to exercise are warranted to build upon these novel findings.NEW & NOTEWORTHY These are the first data to show the influence of preexercise protein on serum and skeletal muscle metabolic adaptations to acute and short-term sprint interval training (SIT). Preexercise whey protein concentrate (WPC) or hydrolysate (WPH) feeding acutely affected the serum metabolome, which differentially influenced acute and chronic changes in mitochondrial gene expression, intracellular signaling (acetylation and PARylation) resulting in either similar or enhanced performance outcomes when compared with fasted training.
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9.
Effect of Dosage Reduction of Hypoglycemic Multidrug Regimens on the Incidences of Acute Glycemic Complications in People With Type 2 Diabetes Who Fast During Ramaḍān: A Randomized Controlled Trial.
Zaghlol, LY, Beirat, AF, Amarin, JZ, Hassoun Al Najar, AM, Hasan, YY, Qtaishat, A, Tierney, ME, Zaghlol, RY, Zayed, AA
Frontiers in endocrinology. 2021;:613826
Abstract
OBJECTIVE We aimed to investigate the effect of dosage reduction of four hypoglycemic multidrug regimens on the incidences of acute glycemic complications in people with type 2 diabetes who fast during Ramaḍān. METHODS We conducted an open-label, parallel-group, randomized controlled trial at a tertiary care center in Amman, Jordan. We recruited adults with type 2 diabetes who expressed an intention to fast during Ramaḍān and were adherent to one of four regimens-namely: metformin and glimepiride; metformin and vildagliptin; metformin and insulin glargine U100; or, metformin, insulin glargine U100, and human regular insulin. We randomly assigned participants in a 2:1 ratio to low- or regular-dosage therapy. The primary outcomes were the incidences of hypoglycemia and hyperglycemia during the 29 days of Ramaḍān 2017, and the secondary outcomes were the incidences of diabetic ketoacidosis and hyperosmolar hyperglycemic state during the same period. RESULTS We randomly assigned 687 participants to low-dosage therapy (n = 458) or regular-dosage therapy (n = 229) and included 678 (452 and 226, respectively) in the final analysis. The incidence of hypoglycemia was lower in the low-dosage group compared with the regular-dosage group (19 [4.2%] vs. 52 [23.0%], respectively; OR, 0.15 [95% CI, 0.08-0.26]; P < 0.001). The incidence of hyperglycemia did not differ between the low- and regular-dosage groups (319 [70.6%] vs. 154 [68.1%], respectively; OR, 1.12 [95% CI, 0.79-1.58]; P = 0.5). No participants experienced diabetic ketoacidosis or hyperosmolar hyperglycemic state. Each 1% decrease in the baseline HbA1c concentration was associated with a 19.9-fold (95% CI, 9.6-41.5; P < 0.001) increase in the odds of hypoglycemia, and each 1% increase in the baseline HbA1c concentration was associated with a 15.7-fold (95% CI, 10.0-24.6; P < 0.001) increase in the odds of hyperglycemia. CONCLUSION Dosage reduction decreases the incidence of hypoglycemia without a concomitant increase in the incidences of hyperglycemia, diabetic ketoacidosis, and hyperosmolar hyperglycemic state in people with type 2 diabetes who fast during Ramaḍān. CLINICAL TRIAL REGISTRATION www.ClinicalTrials.gov, identifier NCT04237493.
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10.
[Intermittent fasting : A solution for metabolic disorders?].
Collet, TH, Pataky, Z
Revue medicale suisse. 2021;(720-1):59-62
Abstract
The management of obesity comprises lifestyle changes targeting nutrient content, eating behavior and regular physical activity. Medication (orlistat, liraglutide) and bariatric surgery can later be used, but they require a clear indication and a close follow-up. Studies in chronobiology are now exploring the metabolic benefits of intermittent fasting, which restricts food intake and calorie-containing beverages to a certain window of the 24h cycle, or to certain days of the week/month, thus reinstating the alternance between anabolism and catabolism. However, the current scientific evidence is limited by the sample size and duration of the studies. It is therefore too early for a blanket strategy based on intermittent fasting in all patients with metabolic disorders.