Mitochondrial dysfunction during in vitro hepatocyte steatosis is reversed by omega-3 fatty acid–induced up-regulation of mitofusin 2

Zhang, Yong; Li, Jiang; Hu, Wenjun; Zheng, Qi; Xiang, Wenpei

doi:10.1016/j.metabol.2010.07.026

Cited by 65 publications

(57 citation statements)

References 48 publications

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“…This was also accompanied by enhanced abundance of ROS. Human derived HepG2 cells displayed a similar fragmented profission phenotype 24 h after supplementation with palmitate (154,156). Fragmented mitochondria corresponded to a significant decrease in the cellular ATP levels, in agreement with mouse hepatocyte studies where mitochondrial membrane potential was lost and enhanced ROS abundance was observed.…”

Section: Metabolic Insult and Mitochondrial Dynamicssupporting

confidence: 84%

“…Fragmented mitochondria corresponded to a significant decrease in the cellular ATP levels, in agreement with mouse hepatocyte studies where mitochondrial membrane potential was lost and enhanced ROS abundance was observed. Interestingly, a coordinate reduction in the abundance of Mfn2 at both transcript and protein levels was observed in the same time course (156). Simplistically, this suggests that the observed fragmented swollen mitochondria in patients with NASH could in fact be the result of decreased expression of the profusion GTPase Mfn2.…”

Section: Metabolic Insult and Mitochondrial Dynamicsmentioning

confidence: 63%

“…It was shown that incubation of HepG2 cells and primary mouse hepatocytes with palmitate fragmented mitochondria (82,154,156). In the case of primary mouse hepatocytes, incubation with palmitate, but not unsaturated fatty acids, resulted in the loss of mitochondrial membrane potential, assessed by tetramethylrhodamine methyl ester fluorescence, and an observed release of cytochrome c into the cytoplasm (82).…”

Section: Metabolic Insult and Mitochondrial Dynamicsmentioning

confidence: 99%

“…Alternatively, it may represent an inhibition of mitochondrial fusion, which would not allow the proper mixing of mitochondrial components. As discussed above in the context of NAFLD, while enhanced abundance of FFA can induce mitochondrial fission supporting the fragmented phenotype, whether this is the result of increased fission or decreased fusion will require further investigation (154,156). It will be informative to examine changes in the abundance of fission and fusion factors in DCM, as studied in the in vitro palmitate treatment of HepG2 cells (156).…”

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confidence: 99%

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Mitochondrial Morphology in Metabolic Diseases

Galloway

Yoon

2013

Antioxidants & Redox Signaling

118

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Significance: Mitochondria are the cellular energy-producing organelles and are at the crossroad of determining cell life and death. As such, the function of mitochondria has been intensely studied in metabolic disorders, including diabetes and associated maladies commonly grouped under all-inclusive pathological condition of metabolic syndrome. More recently, the altered metabolic profiles and function of mitochondria in these ailments have been correlated with their aberrant morphologies. This review describes an overview of mitochondrial fission and fusion machineries, and discusses implications of mitochondrial morphology and function in these metabolic maladies. Recent Advances: Mitochondria undergo frequent morphological changes, altering the mitochondrial network organization in response to environmental cues, termed mitochondrial dynamics. Mitochondrial fission and fusion mediate morphological plasticity of mitochondria and are controlled by membrane-remodeling mechanochemical enzymes and accessory proteins. Growing evidence suggests that mitochondrial dynamics play an important role in diabetes establishment and progression as well as associated ailments, including, but not limited to, metabolism-secretion coupling in the pancreas, nonalcoholic fatty liver disease progression, and diabetic cardiomyopathy. Critical Issues: While mitochondrial dynamics are intimately associated with mitochondrial bioenergetics, their cause-and-effect correlation remains undefined in metabolic diseases. Future Directions: The involvement of mitochondrial dynamics in metabolic diseases is in its relatively early stages. Elucidating the role of mitochondrial dynamics in pathological metabolic conditions will aid in defining the intricate form-function correlation of mitochondria in metabolic pathologies and should provide not only important clues to metabolic disease progression, but also new therapeutic targets. Antioxid. Redox Signal. 19,[415][416][417][418][419][420][421][422][423][424][425][426][427][428][429][430]

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Section: Metabolic Insult and Mitochondrial Dynamicssupporting

confidence: 84%

Section: Metabolic Insult and Mitochondrial Dynamicsmentioning

confidence: 63%

Section: Metabolic Insult and Mitochondrial Dynamicsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Mitochondrial Morphology in Metabolic Diseases

Galloway

Yoon

2013

Antioxidants & Redox Signaling

118

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“…In addition, consumption of a diet supplemented with krill oil has been shown to significantly lower circulating levels of plasma 2-AG in obese human subjects (6). In accord with these observations, PUFAs have been shown to either preserve or improve mitochondrial respiratory function (91,161). However, as yet, it is not known to what extent dietary-induced improvements in ECS function are responsible for enhanced mitochondrial capacity.…”

Section: The Ecs-mitochondrial Axis: a Regulator Of Pancreatic Islet mentioning

confidence: 93%

Mitochondria: a possible nexus for the regulation of energy homeostasis by the endocannabinoid system?

Lipina

Irving

Hundal

2014

American Journal of Physiology-Endocrinology and Metabolism

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Essential lipid autacoids rewire mitochondrial energy efficiency in metabolic dysfunction‐associated fatty liver disease

et al. 2022

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Background and Aim: Injury to hepatocyte mitochondria is common in metabolic dysfunction-associated fatty liver disease. Here, we investigated whether changes in the content of essential fatty acid-derived lipid autacoids affect hepatocyte mitochondrial bioenergetics and metabolic efficiency. Approach and Results:The study was performed in transgenic mice for the fat-1 gene, which allows the endogenous replacement of the membrane omega-6-polyunsaturated fatty acid (PUFA) composition by omega-3-PUFA. Transmission electron microscopy revealed that hepatocyte mitochondria of fat-1 mice had more abundant intact cristae and higher mitochondrial aspect ratio.

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Mitochondrial dysfunction during in vitro hepatocyte steatosis is reversed by omega-3 fatty acid–induced up-regulation of mitofusin 2

Cited by 65 publications

References 48 publications

Mitochondrial Morphology in Metabolic Diseases

Mitochondrial Morphology in Metabolic Diseases

Mitochondria: a possible nexus for the regulation of energy homeostasis by the endocannabinoid system?

Essential lipid autacoids rewire mitochondrial energy efficiency in metabolic dysfunction‐associated fatty liver disease

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