Energy transfer between the mitochondrial network and lipid droplets in insulin resistant skeletal muscle

Parry, Hailey A.

doi:10.1016/j.cophys.2022.100487

Cited by 11 publications

(12 citation statements)

References 73 publications

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“…Since we observed an increased IMCL content in combination with increased 24 h fat oxidation, we hypothesized that the interaction between LDs and mitochondria increase after dapagliflozin treatment [ 41 ]. However, the confocal microscopy analysis did not reveal an increased interaction between LDs and mitochondria (All fibers: −0.94 (−2.62–0.74) %, p = 0.20; Type I: −1.76 (−4.01–0.48) %, p = 0.06; Type II: −0.59 (−2.79–1.62) %, p = 0.51, Suppl.…”

Section: Resultsmentioning

confidence: 99%

Effects of SGLT2 inhibitor dapagliflozin in patients with type 2 diabetes on skeletal muscle cellular metabolism

Kamp¹,

Gemmink²,

Ligt³

et al. 2022

Molecular Metabolism

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Section: Resultsmentioning

confidence: 99%

Effects of SGLT2 inhibitor dapagliflozin in patients with type 2 diabetes on skeletal muscle cellular metabolism

Kamp¹,

Gemmink²,

Ligt³

et al. 2022

Molecular Metabolism

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“…Another potential explanation for this subsarcolemmal‐derived LD–mitochondria contact may be fatty acid trafficking from this region towards centrally located intermyofibrillar LDs. As mitochondria directly interact with other mitochondria around myofibrils, forming a specialized network proposed to distribute energy throughout the entire cell, the funnelling of fatty acids between subcellular compartments could rely on region‐specific functions (Parry & Glancy, 2021; Willingham et al., 2021). Intriguingly, as exercise training more profoundly affects mitochondrial density (Nielsen et al., 2010; Koh et al., 2018; de Almeida et al., 2023) and oxidative capacity (Bizeau et al., 1998; Koves et al., 2005) in the subsarcolemmal space than in the intermyofibrillar space, the profound changes in LD–mitochondria contact in the subsarcolemmal space may also represent higher plasticity of this specific compartment.…”

Section: Discussionmentioning

confidence: 99%

“…The physical contact between LDs and mitochondria is generally considered a direct pathway for fatty acid delivery to the mitochondrion (Parry & Glancy, 2021), thereby supporting ATP maintenance during exercise. This notion is in line with recent data indicating that mitochondria bound to LDs may also have differential cellular functions than their non‐interacting counterparts (Bleck et al., 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Intriguingly, as exercise training more profoundly affects mitochondrial density (Nielsen et al, 2010;Koh et al, 2018;de Almeida et al, 2023) and oxidative capacity (Bizeau et al, 1998;Koves et al, 2005) in the subsarcolemmal space than in the intermyofibrillar space, the profound changes in LD-mitochondria contact in the subsarcolemmal space may also represent higher plasticity of this specific compartment. The physical contact between LDs and mitochondria is generally considered a direct pathway for fatty acid delivery to the mitochondrion (Parry & Glancy, 2021), thereby supporting ATP maintenance during exercise. This notion is in line with recent data indicating that mitochondria bound to LDs may also have differential cellular functions than their non-interacting counterparts (Bleck et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…The interconnected nature of the mitochondrial network in the skeletal muscle provides a rapid mechanism for energy production and cellular distribution during exercise (Bleck et al., 2018). The intramuscular mitochondria also form physical membrane‐to‐membrane contact with triacylglycerol (TAG) containing lipid droplets (LDs), which is considered a direct pathway for fatty acid delivery to the mitochondrion for β‐oxidation (Parry & Glancy, 2021). The experimental findings forming this idea were first demonstrated by increased contact after exercise training (Tarnopolsky et al., 2007) and after acute exercise in women but not men (Devries et al., 2007).…”

Section: Introductionmentioning

confidence: 99%

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Acute exercise increases the contact between lipid droplets and mitochondria independently of obesity and type 2 diabetes

Almeida

Ørtenblad

Petersen

et al. 2023

The Journal of Physiology

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Intramuscular lipid droplets (LDs) and mitochondria are essential organelles in cellular communication and metabolism, supporting local energy demands during muscle contractions. While insulin resistance impacts cellular functions and systems within the skeletal muscle, it remains unclear whether the interaction of LDs and mitochondria is affected by exercise and the role of obesity and type 2 diabetes. By employing transmission electron microscopy (TEM), we aimed to investigate the effects of 1 h of ergometry cycling on LD morphology, subcellular distribution and mitochondrial contact in skeletal muscle fibres of patients with type 2 diabetes and glucose‐tolerant lean and obese controls, matched for equal exercise intensities. Exercise did not change LD volumetric density, numerical density, profile size or subcellular distribution. However, evaluated as the magnitude of inter‐organelle contact, exercise increased the contact between LDs and mitochondria with no differences between the three groups. This effect was most profound in the subsarcolemmal space of type 1 muscle fibres, and here the absolute contact length increased on average from ∼275 to ∼420 nm. Furthermore, the absolute contact length before exercise (ranging from ∼140 to ∼430 nm) was positively associated with the fat oxidation rate during exercise. In conclusion, we showed that acute exercise did not mediate changes in the LD volume fractions, numbers or size but increased the contact between LDs and mitochondria, irrespective of obesity or type 2 diabetes. These data suggest that the increased LD–mitochondria contact with exercise is not disturbed in obesity or type 2 diabetes. Key points Type 2 diabetes is associated with altered interactivity between lipid droplets (LDs) and mitochondria in the skeletal muscle. Physical contact between the surface of LDs and the surrounding mitochondrial network is considered favourable for fat oxidation. We show that 1 h of acute exercise increases the length of contact between LDs and mitochondria, irrespective of obesity or type 2 diabetes. This contact length between LDs and mitochondria is not associated with a net decrease in the LD volumetric density after the acute exercise. However, it correlates with the fat oxidation rate during exercise. Our data establish that exercise mediates contact between LDs and the mitochondrial network and that this effect is not impaired in individuals with type 2 diabetes or obesity.

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Ethnicity‐related differences in mitochondrial regulation by insulin stimulation in diabetes

Neikirk,

Kabugi,

Mungai

et al. 2024

Journal Cellular Physiology

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Mitochondrial dysfunction has long been implicated in the development of insulin resistance, which is a hallmark of type 2 diabetes. However, recent studies reveal ethnicity‐related differences in mitochondrial processes, underscoring the need for nuance in studying mitochondrial dysfunction and insulin sensitivity. Furthermore, the higher prevalence of type 2 diabetes among African Americans and individuals of African descent has brought attention to the role of ethnicity in disease susceptibility. In this review, which covers existing literature, genetic studies, and clinical data, we aim to elucidate the complex relationship between mitochondrial alterations and insulin stimulation by considering how mitochondrial dynamics, contact sites, pathways, and metabolomics may be differentially regulated across ethnicities, through mechanisms such as single nucleotide polymorphisms (SNPs). In addition to achieving a better understanding of insulin stimulation, future studies identifying novel regulators of mitochondrial structure and function could provide valuable insights into ethnicity‐dependent insulin signaling and personalized care.

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Energy transfer between the mitochondrial network and lipid droplets in insulin resistant skeletal muscle

Cited by 11 publications

References 73 publications

Effects of SGLT2 inhibitor dapagliflozin in patients with type 2 diabetes on skeletal muscle cellular metabolism

Effects of SGLT2 inhibitor dapagliflozin in patients with type 2 diabetes on skeletal muscle cellular metabolism

Acute exercise increases the contact between lipid droplets and mitochondria independently of obesity and type 2 diabetes

Ethnicity‐related differences in mitochondrial regulation by insulin stimulation in diabetes

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