Metabolic inflexibility in youth with obesity: Is it a feature of obesity or distinctive of youth who are metabolically unhealthy?

2021 ◽  
Author(s):  
Nour Y. Gebara ◽  
Joon Young Kim ◽  
Fida Bacha ◽  
SoJung Lee ◽  
Silva Arslanian
Keyword(s):  
Metabolic Inflexibility

scholarly journals Metabolic inflexibility of white and brown adipose tissues in abnormal fatty acid partitioning of type 2 diabetes

2012 ◽  
Vol 2 (S2) ◽  
pp. S37-S42 ◽  
Author(s):  
T Grenier-Larouche ◽  
S M Labbé ◽  
C Noll ◽  
D Richard ◽  
A C Carpentier
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Adipose Tissues ◽  
Brown Adipose ◽  
Metabolic Inflexibility

scholarly journals Branched-Chain Amino Acid Metabolism is Regulated by ERRα and is Further Impaired by Glucose Loading in Type 2 Diabetes

2020 ◽  
Author(s):  
Rasmus J.O. Sjögren ◽  
David Rizo-Roca ◽  
Alexander V. Chibalin ◽  
Elin Chorell ◽  
Regula Furrer ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasma Metabolites ◽  
Peripheral Tissues ◽  
Branched Chain Amino Acid ◽  
Glucose Challenge ◽  
Metabolic Inflexibility ◽  
Branched Chain ◽  
Estrogen Related Receptor ◽  
Dependent Mechanism

SUMMARYIncreased levels of branched-chain amino acids (BCAAs) are associated with type 2 diabetes (T2D) pathogenesis. However, most metabolomic studies in T2D are limited to an analysis of plasma metabolites under fasting conditions, rather than the dynamic shift in response to a glucose challenge. Moreover, metabolomic profiles of peripheral tissues involved in glucose homeostasis are scarce and the transcriptomic regulation of genes involved in BCAA catabolism in T2D is partially unknown. Using metabolomic and gene expression approaches, we found that impairments in BCAA catabolism in T2D patients under fasting conditions are exacerbated after a glucose load, concomitant with downregulated expression of BCAA-related genes in skeletal muscle. We identified a key regulatory role for Estrogen-Related Receptor α (ERRα) in PGC-1α-mediated upregulation of BCAA genes and leucine oxidation. Thus, metabolic inflexibility in T2D impacts BCAA homeostasis and the transcriptional regulation of BCAA genes via a PGC-1α/ERRα-dependent mechanism.

scholarly journals Cardiorespiratory Fitness May Influence Metabolic Inflexibility During Exercise in Obese Persons

2019 ◽  
Vol 104 (12) ◽  
pp. 5780-5790 ◽  
Author(s):  
Francisco J Amaro-Gahete ◽  
Guillermo Sanchez-Delgado ◽  
Ignacio Ara ◽  
Jonatan R. Ruiz
Keyword(s):  
Cardiorespiratory Fitness ◽  
Lean Mass ◽  
Normal Weight ◽  
Whole Body ◽  
Graded Exercise ◽  
Obese Subjects ◽  
Maximal Fat Oxidation ◽  
Metabolic Inflexibility ◽  
Overweight Subjects ◽  
Body Lean Mass

Abstract Context We examined whether obese individuals have a reduced maximal fat oxidation (MFO) and the intensity that elicit MFO (Fatmax) compared with normal weight and overweight persons, taking into account their level of cardiorespiratory fitness. Methods The study subjects were 138 sedentary adults (87 women) aged 30.1 ± 13.6 years. Based on their body mass index, subjects were categorized as being of normal weight (n = 66), overweight (n = 48), or obese (n = 24). MFO and Fatmax were determined for all subjects by indirect calorimetry, using a walking graded exercise test. MFO was expressed in absolute terms (g/min) and relative to whole-body lean mass (mg/kgleanmass/min). Cardiorespiratory fitness was assessed via a maximal treadmill test. Results No differences in absolute MFO and Fatmax values were seen between the obese, normal weight, and overweight subjects (all P > 0.2), although after adjusting for cardiorespiratory fitness, the obese subjects returned significantly higher values than did their normal weight and overweight counterparts (all P < 0.03). However, when expressed with respect to lean mass, the MFO of the normal weight subjects was significantly greater than that of the overweight and obese subjects, independent of age, sex, or cardiorespiratory fitness. Conclusions Obese individuals have higher absolute MFO values when cardiorespiratory fitness is taken into account, but when expressed with respect to lean mass, normal weight individuals show a greater capacity to oxidize fat during exercise per unit of metabolically active tissue independent of age, sex, or cardiorespiratory fitness. These findings suggest that obese individuals may suffer from metabolic inflexibility during exercise.

scholarly journals Differential epigenetic and transcriptional response of the skeletal muscle carnitine palmitoyltransferase 1B (CPT1B) gene to lipid exposure with obesity

2015 ◽  
Vol 309 (4) ◽  
pp. E345-E356 ◽  
Author(s):  
Jill M. Maples ◽  
Jeffrey J. Brault ◽  
Carol A. Witczak ◽  
Sanghee Park ◽  
Monica J. Hubal ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dna Methylation ◽  
Transcription Factor ◽  
Fatty Acid ◽  
Histone Acetylation ◽  
Human Skeletal Muscle ◽  
Epigenetic Modifications ◽  
Carnitine Palmitoyltransferase ◽  
Severely Obese ◽  
Metabolic Inflexibility

The ability to increase fatty acid oxidation (FAO) in response to dietary lipid is impaired in the skeletal muscle of obese individuals, which is associated with a failure to coordinately upregulate genes involved with FAO. While the molecular mechanisms contributing to this metabolic inflexibility are not evident, a possible candidate is carnitine palmitoyltransferase-1B (CPT1B), which is a rate-limiting step in FAO. The present study was undertaken to determine if the differential response of skeletal muscle CPT1B gene transcription to lipid between lean and severely obese subjects is linked to epigenetic modifications (DNA methylation and histone acetylation) that impact transcriptional activation. In primary human skeletal muscle cultures the expression of CPT1B was blunted in severely obese women compared with their lean counterparts in response to lipid, which was accompanied by changes in CpG methylation, H3/H4 histone acetylation, and peroxisome proliferator-activated receptor-δ and hepatocyte nuclear factor 4α transcription factor occupancy at the CPT1B promoter. Methylation of specific CpG sites in the CPT1B promoter that correlated with CPT1B transcript level blocked the binding of the transcription factor upstream stimulatory factor, suggesting a potential causal mechanism. These findings indicate that epigenetic modifications may play important roles in the regulation of CPT1B in response to a physiologically relevant lipid mixture in human skeletal muscle, a major site of fatty acid catabolism, and that differential DNA methylation may underlie the depressed expression of CPT1B in response to lipid, contributing to the metabolic inflexibility associated with severe obesity.

The potential of phototherapy to reduce body fat, insulin resistance and “metabolic inflexibility” related to obesity in women undergoing weight loss treatment

2015 ◽  
Vol 47 (8) ◽  
pp. 634-642 ◽  
Author(s):  
Marcela Sene-Fiorese ◽  
Fernanda Oliveira Duarte ◽  
Antonio Eduardo de Aquino Junior ◽  
Raquel Munhoz da Silveira Campos ◽  
Deborah Cristina Landi Masquio ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Body Fat ◽  
Weight Loss Treatment ◽  
Metabolic Inflexibility

scholarly journals Metabolic flexibility during sleep

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Simeng Zhang ◽  
Yoshiaki Tanaka ◽  
Asuka Ishihara ◽  
Akiko Uchizawa ◽  
Insung Park ◽  
...  
Keyword(s):  
Young Adults ◽  
Time Resolution ◽  
Diurnal Rhythm ◽  
Indirect Calorimetry ◽  
Early Stage ◽  
Metabolic Flexibility ◽  
Extended Duration ◽  
Older Subjects ◽  
Metabolic Inflexibility ◽  
Insight Into

AbstractKnown as metabolic flexibility, oxidized substrate is selected in response to changes in the nutritional state. Sleep imposes an extended duration of fasting, and oxidized substrates during sleep were assumed to progressively shift from carbohydrate to fat, thereby gradually decreasing the respiratory quotient (RQ). Contrary to this assumption, whole-room indirect calorimetry with improved time resolution revealed that RQ re-ascended prior to awakening, and nadir of RQ in non-obese young adults occurred earlier in women than men after bedtime. The transient decrease in RQ during sleep was blunted in metabolically inflexible men with smaller amplitude of diurnal rhythm in RQ. Similarly, the effect of 10 years difference in age on RQ became significant during sleep; the decrease in RQ during sleep was blunted in older subjects. Inter-individual difference in RQ become apparent during sleep, and it might serve as a window to gain insight into the early-stage pathogenesis of metabolic inflexibility.

Octyl gallate triggers dysfunctional mitochondria leading to ROS driven membrane damage and metabolic inflexibility along with attenuated virulence in Candida albicans

2019 ◽  
Vol 58 (3) ◽  
pp. 380-392 ◽  
Author(s):  
Venkata Saibabu ◽  
Zeeshan Fatima ◽  
Kamal Ahmad ◽  
Luqman Ahmad Khan ◽  
Saif Hameed
Keyword(s):  
Candida Albicans ◽  
Isocitrate Lyase ◽  
Membrane Damage ◽  
Carbon Sources ◽  
Antifungal Drugs ◽  
In Vivo Studies ◽  
Haemolytic Activity ◽  
Metabolic Inflexibility ◽  
Underlying Mechanisms

Abstract Recently the high incidence of worldwide Candida infections has substantially increased. The growing problem about toxicity of antifungal drugs and multidrug resistance aggravates the need for the development of new effective strategies. Natural compounds in this context represent promising alternatives having potential to be exploited for improving human health. The present study was therefore designed to evaluate the antifungal effect of a naturally occurring phenolic, octyl gallate (OG), on Candida albicans and to investigate the underlying mechanisms involved. We demonstrated that OG at 25 μg/ml could effectively inhibit C. albicans. Mechanistic insights revealed that OG affects mitochondrial functioning as Candida cells exposed to OG did not grow on non-fermentable carbon sources. Dysfunctional mitochondria triggered generation of reactive oxygen species (ROS), which led to membrane damage mediated by lipid peroxidation. We explored that OG inhibited glucose-induced reduction in external pH and causes decrement in ergosterol levels by 45%. Furthermore, OG impedes the metabolic flexibility of C. albicans by inhibiting the glyoxylate enzyme isocitrate lyase, which was also confirmed by docking analysis. Additionally, OG affected virulence traits such as morphological transition and cell adherence. Furthermore, we depicted that OG not only prevented biofilm formation but eliminates the preformed biofilms. In vivo studies with Caenorhabditis elegans nematode model confirmed that OG could enhance the survival of C. elegans after infection with Candida. Toxicity assay using red blood cells showed only 27.5% haemolytic activity. Taken together, OG is a potent inhibitor of C. albicans that warrants further structural optimization and pharmacological investigations.

scholarly journals Inflexibility of the plasma miRNA response following a high-carbohydrate meal in overweight insulin-resistant women

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
F. Ramzan ◽  
R. F. D’Souza ◽  
B. R. Durainayagam ◽  
A. M. Milan ◽  
N. C. Roy ◽  
...  
Keyword(s):  
Metabolic Regulation ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Trial Registration ◽  
Healthy Weight ◽  
Peripheral Blood Mononuclear ◽  
Insulin Resistant ◽  
High Carbohydrate ◽  
Metabolic Inflexibility ◽  
Carbohydrate Meal

Abstract Context Metabolic inflexibility is a characteristic of insulin resistance, limiting the ability to transiently regulate oxidative metabolism and gene expression in response to nutrient availability. Little is known of the flexibility of post-transcriptional regulation, including circulatory miRNAs (c-miRNAs). Design The abundances of targeted c-miRNAs, with reported functions in metabolic regulation, were analysed in response to a high-carbohydrate meal in healthy weight insulin-sensitive (IS) and overweight insulin-resistant (IR) women. Participants Age-matched healthy weight IS (n = 20, BMI = 24.3 ± 0.70) and overweight IR (n = 20, BMI = 28.6 ± 0.67) women. Methods An abundance of c-miRNAs was quantified prior to and following a high-carbohydrate breakfast meal (2500 kJ; 50% carbohydrate, 20% fat and 27% protein). Target genes of the differentially regulated c-miRNA were measured in RNA extracted from circulatory peripheral blood mononuclear cells (PBMCs). Results In healthy weight IS women, both miR-15a-5p (p = 0.03) and miR-17-5p (p < 0.01) levels were halved at 4 h post-meal. These miRNA remained unaltered following the same meal in the overweight IR women. Furthermore, amongst genes targeted by these miRNA, CPT1A (p = 0.01) and IL8 (p = 0.03) had also reduced expression 4 h post-meal only in the healthy weight IS women. Conclusions The study findings provide preliminary evidence for a possible extension of metabolic inflexibility to include c-miRNAs. Trial registration The clinical trial is registered with Australian New Zealand Clinical Trials Registry under Trial registration: ANZCTR: ACTRN12615001108505. Registered on 21 October 2015.

scholarly journals Metabolic inflexibility in women with polycystic ovary syndrome: a systematic review

2019 ◽  
Vol 36 (6) ◽  
pp. 501-507 ◽  
Author(s):  
Michael Rimmer ◽  
Bee K. Tan ◽  
Helena Teede ◽  
Shakila Thangaratinam ◽  
Bassel H. Al Wattar
Keyword(s):  
Systematic Review ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Metabolic Inflexibility
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