Subpopulation-specific differences in skeletal muscle mitochondria in humans with obesity: insights from studies employing acute nutritional and exercise stimuli

Wahwah, Nisreen; Kras, Katon A.; Roust, Lori R.; Katsanos, Christos S.

doi:10.1152/ajpendo.00463.2019

Cited by 8 publications

(3 citation statements)

References 143 publications

(274 reference statements)

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“…Moreover, detrimental effects were observed for almost every other aspect of mitochondrial metabolism directly connected with mitochondrial respiration, namely TCA cycle, membrane potential and OXPHOS (90). Interestingly, both in animal and human models it was demonstrated that negative effects of obesity on mitochondrial function could be ameliorated by the stimulation of muscle contraction, which both improves the mitochondrial respiratory function and corrects mitochondrial morphological changes (91,92). In line with the above findings, it was observed that muscle contraction reduces global ceramide content, which improves insulin-stimulated glucose uptake (91).…”

Section: Inhibition Of Mitochondrial Respiration By Ceramide Accumulamentioning

confidence: 99%

Sphingolipids as a Culprit of Mitochondrial Dysfunction in Insulin Resistance and Type 2 Diabetes

Roszczyc-Owsiejczuk

Zabielski

2021

Front. Endocrinol.

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Insulin resistance is defined as a complex pathological condition of abnormal cellular and metabolic response to insulin. Obesity and consumption of high-fat diet lead to ectopic accumulation of bioactive lipids in insulin-sensitive tissues. Intracellular lipid accumulation is regarded as one of the major factors in the induction of insulin resistance and type 2 diabetes (T2D). A significant number of studies have described the involvement of ceramides and other sphingolipids in the inhibition of insulin-signaling pathway in both skeletal muscles and the liver. Adverse effects of sphingolipid accumulation have recently been linked to the activation of protein kinase Cζ (PKCζ) and protein phosphatase 2A (PP2A), which, in turn, negatively affect phosphorylation of serine/threonine kinase Akt [also known as protein kinase B (PKB)], leading to decreased glucose uptake in skeletal muscles as well as increased gluconeogenesis and glycogenolysis in the liver. Sphingolipids, in addition to their direct impact on the insulin signaling pathway, may be responsible for other negative aspects of diabetes, namely mitochondrial dysfunction and deficiency. Mitochondrial health, which is characterized by appropriate mitochondrial quantity, oxidative capacity, controlled oxidative stress, undisturbed respiratory chain function, adenosine triphosphate (ATP) production and mitochondrial proliferation through fission and fusion, is impaired in the skeletal muscles and liver of T2D subjects. Recent findings suggest that impaired mitochondrial function may play a key role in the development of insulin resistance. Mitochondria stay in contact with the endoplasmic reticulum (ER), Golgi membranes and mitochondria-associated membranes (MAM) that are the main places of sphingolipid synthesis. Moreover, mitochondria are capable of synthesizing ceramide though ceramide synthase (CerS) activity. Recently, ceramides have been demonstrated to negatively affect mitochondrial respiratory chain function and fission/fusion activity, which is also a hallmark of T2D. Despite a significant correlation between sphingolipids, mitochondrial dysfunction, insulin resistance and T2D, this subject has not received much attention compared to the direct effect of sphingolipids on the insulin signaling pathway. In this review, we focus on the current state of scientific knowledge regarding the involvement of sphingolipids in the induction of insulin resistance by inhibiting mitochondrial function.

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Section: Inhibition Of Mitochondrial Respiration By Ceramide Accumulamentioning

confidence: 99%

Sphingolipids as a Culprit of Mitochondrial Dysfunction in Insulin Resistance and Type 2 Diabetes

Roszczyc-Owsiejczuk

Zabielski

2021

Front. Endocrinol.

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“…In skeletal muscles of type 2 diabetes subjects [ 46 , 47 , 48 , 49 ], insulin-resistant offspring of type 2 diabetes subjects, and obese individuals [ 47 ], disturbance of mitochondrial respiration was observed when compared to lean normal controls. Interestingly, chronic muscle stimulation, which improves the mitochondrial respiratory function and corrects mitochondrial morphological changes [ 50 , 51 ], ameliorates mitochondrial function in obesity by reducing muscle ceramide content and improving insulin-stimulated glucose uptake [ 50 ].…”

Section: Sphingolipids Obesity and Insulin Resistancementioning

confidence: 99%

Circulating Sphingolipids in Insulin Resistance, Diabetes and Associated Complications

Hammad,

Lopes-Virella

2023

IJMS

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Sphingolipids play an important role in the development of diabetes, both type 1 and type 2 diabetes, as well as in the development of both micro- and macro-vascular complications. Several reviews have been published concerning the role of sphingolipids in diabetes but most of the emphasis has been on the possible mechanisms by which sphingolipids, mainly ceramides, contribute to the development of diabetes. Research on circulating levels of the different classes of sphingolipids in serum and in lipoproteins and their importance as biomarkers to predict not only the development of diabetes but also of its complications has only recently emerged and it is still in its infancy. This review summarizes the previously published literature concerning sphingolipid-mediated mechanisms involved in the development of diabetes and its complications, focusing on how circulating plasma sphingolipid levels and the relative content carried by the different lipoproteins may impact their role as possible biomarkers both in the development of diabetes and mainly in the development of diabetic complications. Further studies in this field may open new therapeutic avenues to prevent or arrest/reduce both the development of diabetes and progression of its complications.

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“…Physical exercise, in conjunction with lifestyle changes, is widely recognized as the most effective non-pharmacological intervention for improving cardiorespiratory fitness and managing chronic diseases. Recent research has shown that exercise can counteract the negative effects of obesity on mitochondria and foster the growth of a healthy mitochondrial population by altering processes such as mitogenesis, fission, and mitophagy [8][9][10][11][12][13]. However, the underlying mechanisms and their impact on the mitochondrial dynamics processes have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Effects of fission and mitophagy on mitochondrial functionality under accelerated damage conditions: A mathematical modeling approach

Zamora-Ramírez

Santillán

2023

Front. Appl. Math. Stat.

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There is growing evidence that mitochondrial dynamics play a role in mitochondrial function quality control. Recent studies have discovered that physical activity can aid in maintaining a healthy mitochondrial population and may even counteract the mitochondrial damage caused by obesity by modifying mitochondrial dynamics processes like mitogenesis, fission, and mitophagy. However, the underlying mechanisms and how they influence the various processes of mitochondrial dynamics have not been completely clarified. This study seeks to make an initial effort to fill this gap by utilizing mathematical modeling to investigate how modifications to the processes involved in mitochondrial dynamics can aid in preserving a healthy mitochondrial population under conditions of accelerated damage. We found by analyzing the model stationary behavior that fission and mitophagy are strictly required for a healthy mitochondrial population, that increasing the rate of mitochondrial damage has a negative impact on the population of functional mitochondria, and that such damage can be mitigated to some extent by increasing fission and/or mitophagy rates. These findings are finally discussed in the context of the benefits of physical activity for mitochondrial population health in obese individuals.

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Subpopulation-specific differences in skeletal muscle mitochondria in humans with obesity: insights from studies employing acute nutritional and exercise stimuli

Cited by 8 publications

References 143 publications

Sphingolipids as a Culprit of Mitochondrial Dysfunction in Insulin Resistance and Type 2 Diabetes

Sphingolipids as a Culprit of Mitochondrial Dysfunction in Insulin Resistance and Type 2 Diabetes

Circulating Sphingolipids in Insulin Resistance, Diabetes and Associated Complications

Effects of fission and mitophagy on mitochondrial functionality under accelerated damage conditions: A mathematical modeling approach

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