Pathophysiological role of metabolic flexibility on metabolic health

Galgani, José E.; Fernández‐Verdejo, Rodrigo

doi:10.1111/obr.13131

Cited by 50 publications

(74 citation statements)

References 128 publications

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“…Finally, the differences in LDL‐C between groups (higher in Mfn2‐LA group) may represent the initial steps toward a disturbed lipid profile mediated by decreases in Mfn2 protein in SM. This could result from a reduced tissular capacity to adapt fuel oxidation to fuel availability, that is, an impaired metabolic flexibility 35 . We have recently shown that healthy subjects with low metabolic flexibility have higher circulating LDL‐C than subjects with high metabolic flexibility 36 .…”

Section: Discussionmentioning

confidence: 99%

Low abundance of Mfn2 protein correlates with reduced mitochondria‐SR juxtaposition and mitochondrial cristae density in human men skeletal muscle: Examining organelle measurements from TEM images

et al. 2021

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The role of mitofusin 2 (Mfn2) in the regulation of skeletal muscle (SM) mitochondriasarcoplasmic (SR) juxtaposition, mitochondrial morphology, mitochondrial cristae density (MCD), and SM quality has not been studied in humans. In in vitro studies, whether Mfn2 increases or decreases mitochondria-SR juxtaposition remains controversial. Transmission electron microscopy (TEM) images are commonly used to measure the organelle juxtaposition, but the measurements are performed "by-hand," thus potentially leading to between-rater differences. The purposes of this study were to: (1) examine the repeatability and reproducibility of mitochondrial-SR juxtaposition measurement from TEM images of human SM between three raters with different experience and (2) compare the mitochondrial-SR juxtaposition, mitochondrial morphology, MCD (stereological-method), and SM quality (cross-sectional area [CSA] and the maximum voluntary contraction [MVC]) between subjects with high abundance (Mfn2-HA; n = 6) and low abundance (Mfn2-LA; n = 6) of Mfn2 protein. The mitochondria-SR juxtaposition had moderate repeatability and reproducibility, with the most experienced raters showing the best values. There were no differences between Mfn2-HA and Mfn2-LA groups in mitochondrial size, distance from mitochondria to SR, CSA, or MVC. Nevertheless, the Mfn2-LA group showed lower 2 of 12 | CASTRO-SEPULVEDA ET AL.

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Section: Discussionmentioning

confidence: 99%

Low abundance of Mfn2 protein correlates with reduced mitochondria‐SR juxtaposition and mitochondrial cristae density in human men skeletal muscle: Examining organelle measurements from TEM images

et al. 2021

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“…Different Metflex markers have been physiologically related to physical fitness and insulin sensitivity [ 2 , 4 , 6 , 8 , 10 , 13 , 14 , 24 ]. The present study aimed to determine their correlation particularly testing their association with body fatness while controlling for VO 2peak (mL∙kg −1 ∙min −1 ) in subjects with obesity.…”

Section: Discussionmentioning

confidence: 99%

“…On the contrary, this work demonstrates that 46% of TFO’s associated variance is explained by MFO, and the latter shows an inverse relationship with the RER peak ( p < 0.01) and so, MFO is a valid marker of dynamic substrate selection (fueling) during submaximal exercise. Measurement of the fat oxidation increase in response to submaximal exercise is a valid strategy for Metflex assessment [ 2 , 4 ], future studies need to analyze whether MFO, TFO and RER peak are associated with postprandial fat oxidation after a high fat meal and nutrient oxidation during the sleep period, conditions that require Metflex.…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, a reduced fat oxidation capacity (a.k.a. metabolic inflexibility (Metinflex)) is a typical feature in obesity due to a reduced muscle mitochondrial volume-density, adipogenesis, and reduced activity of carnitine palmitoyltransferase-1 (CPT-1), citrate synthase, and cytochrome c oxidase [ 3 , 4 ]. Metinflex may promotes the deposition of ceramides and diacylglycerol in skeletal muscle resulting on insulin resistance [ 5 ], although systematic evidence contradicts the aforementioned paradigm.…”

Section: Introductionmentioning

confidence: 99%

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Exercise Fat Oxidation Is Positively Associated with Body Fatness in Men with Obesity: Defying the Metabolic Flexibility Paradigm

Chávez-Guevara

Hernández-Torres

Trejo-Trejo

et al. 2021

IJERPH

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Obesity is thought to be associated with a reduced capacity to increase fat oxidation in response to physical exercise; however, scientific evidence supporting this paradigm remains scarce. This study aimed to determine the interrelationship of different submaximal exercise metabolic flexibility (Metflex) markers and define its association with body fatness on subjects with obesity. Twenty-one male subjects with obesity performed a graded-intensity exercise protocol (Test 1) during which cardiorespiratory fitness (CRF), maximal fat oxidation (MFO) and its corresponding exercise intensity (FATmax) were recorded. A week afterward, each subject performed a 60-min walk (treadmill) at FATmax (Test 2), and the resulting fat oxidation area under the curve (TFO) and maximum respiratory exchange ratio (RERpeak) were recorded. Blood lactate (LAb) levels was measured during both exercise protocols. Linear regression analysis was used to study the interrelationship of exercise Metflex markers. Pearson’s correlation was used to evaluate all possible linear relationships between Metflex and anthropometric measurement, controlling for CRF). The MFO explained 38% and 46% of RERpeak and TFO’s associated variance (p < 0.01) while TFO and RERpeak were inversely related (R2 = 0.54, p < 0.01). Body fatness positively correlated with MFO (r = 0.64, p < 0.01) and TFO (r = 0.63, p < 0.01) but inversely related with RERpeak (r = −0.67, p < 0.01). This study shows that MFO and RERpeak are valid indicators of TFO during steady-state exercise at FATmax. The fat oxidation capacity is directly associated with body fatness in males with obesity.

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“…In Brazil, up to that date, 8,488,099 cases of coronavirus were registered and, of these, 210,299 died due to this pathology. In the state of Sergipe, according to the State Secretariat, 128,395 cases of infection by SARS-CoV-2 and 2662 deaths were identified, with the first case report of this infection in March of 2020 [4,5].…”

Section: Introductionmentioning

confidence: 99%

Epidemiology of COVID-19 in the State of Sergipe/Brazil and Its Relationship with Social Indicators

et al. 2021

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A pandemic is capable of generating a great impact, not only from the point of view of health, but also socioeconomically. In March 2020, the World Health Organization (WHO) declared that a new pandemic situation had arisen, due to the SARS-CoV-2 virus, whose probable origin was zoonotic. The largest number of cases of this disease is concentrated in the United States of America (USA), India, and Brazil. The mortality rate is estimated at 3.4%, but regional differences may exist, and places with a high demographic density have become true epicentres and may be related to higher rates of transmission. In addition to the above, lower human development indexes (HDI) can be related to worse outcomes, especially in the North and Northeast regions of Brazil since they are the least developed places. The Northeast region is the second-most-affected place in the number of COVID-19 cases in Brazil. An analytical observational study of an ecological type was carried out from April to October 2020 to assess the epidemiological situation of COVID-19 in the state of Sergipe and specifically to analyse the incidence of cases and deaths resulting from COVID-19 in the different health regions of the state of Sergipe, in relation to the values of the HDI and demographic density. During the study period, 84,325 cases of COVID-19 were identified, in which 2205 resulted in death. In most of the regions studied, there was a positive association between the number of cases and deaths and the greater the demographic density, but there was no increase in the risk of becoming ill, nor of dying the lower the HDI. Large and crowded cities are places of greatest vulnerability to illness, due to their greater capacity of transmitting the virus; however, further studies are needed to identify other factors that are decisive in the outcomes of this new disease.

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Pathophysiological role of metabolic flexibility on metabolic health

Cited by 50 publications

References 128 publications

Low abundance of Mfn2 protein correlates with reduced mitochondria‐SR juxtaposition and mitochondrial cristae density in human men skeletal muscle: Examining organelle measurements from TEM images

Low abundance of Mfn2 protein correlates with reduced mitochondria‐SR juxtaposition and mitochondrial cristae density in human men skeletal muscle: Examining organelle measurements from TEM images

Exercise Fat Oxidation Is Positively Associated with Body Fatness in Men with Obesity: Defying the Metabolic Flexibility Paradigm

Epidemiology of COVID-19 in the State of Sergipe/Brazil and Its Relationship with Social Indicators

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