Peroxisomal gene and protein expression increase in response to a high-lipid challenge in human skeletal muscle

Huang, Tai‐Yu; Zheng, Donghai; Hickner, Robert C.; Brault, Jeffrey J.; Cortright, Ronald N.

doi:10.1016/j.metabol.2019.06.009

Cited by 11 publications

(11 citation statements)

References 37 publications

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“…We also reported that acute low-intensity exercise induces a rapid, short-term increase in peroxisomal lipid oxidation (19). Additionally, peroxisomal oxidative capacity increases in response to lipid-rich environments in rodent and human muscle (31,64). Data herein extend upon these findings as they are the first to report that vigorous-intensity exercise training increases peroxisomal oxidation in mice fed a low-fat diet; however, while being fed a lipid-rich NPKD, exercise training further induced several peroxisomal genes and proteins in skeletal muscle.…”

Section: Discussionmentioning

confidence: 78%

Combined effects of a ketogenic diet and exercise training alter mitochondrial and peroxisomal substrate oxidative capacity in skeletal muscle

Huang

Linden

Fuller

et al. 2021

American Journal of Physiology-Endocrinology and Metabolism

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Ketogenic diets (KD) are reported to improve body weight, fat mass, and exercise performance in humans. Unfortunately, most rodent studies have used a low-protein KD, which does not recapitulate diets used by humans. Since skeletal muscle plays a critical role in responding to macronutrient perturbations induced by diet and exercise, the purpose of this study was to test if a normal-protein KD (NPKD) impacts shifts in skeletal muscle substrate oxidative capacity in response to exercise training (ExTr). A high fat, carbohydrate-deficient NPKD (16.1% protein, 83.9% fat, 0% carbohydrate) was given to C57BL/6J male mice for 6 weeks, while controls received a low fat diet with similar protein (15.9% protein, 11.9% fat, 72.2% carbohydrate). On week four of the diet, mice began treadmill training 5 days/week, 60 min/day for 3 weeks. NPKD-fed mice increased body weight and fat mass, while ExTr negated a continued rise in adiposity. ExTr increased intramuscular glycogen, while the NPKD increased intramuscular triglycerides. Neither the NPKD nor ExTr alone altered mitochondrial content; however, in combination, the NPKD-ExTr group showed increases in PGC-1α, as well as markers of mitochondrial fission and fusion. Pyruvate oxidative capacity was unchanged by either intervention, while ExTr increased leucine oxidation in NPKD-fed mice. Lipid metabolism pathways had the most notable changes as the NPKD and ExTr interventions both enhanced mitochondrial and peroxisomal lipid oxidation and many adaptations were additive or synergistic. Overall these results suggest a combination of a NPKD and ExTr induces additive and/or synergistic adaptations in skeletal muscle oxidative capacity.

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Section: Discussionmentioning

confidence: 78%

Combined effects of a ketogenic diet and exercise training alter mitochondrial and peroxisomal substrate oxidative capacity in skeletal muscle

Huang

Linden

Fuller

et al. 2021

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

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“…It has been further suggested that these tissues upregulate PGC-1α in response to increased lipid intake, acting as a compensatory mechanism for high fat diets and metabolic dysregulation. This co-regulation of peroxisomal and mitochondrial biogenesis has been established in brown adipose tissue, liver and skeletal muscle ( Huang et al, 2017 , 2019 ; Hevener et al, 2020 ). Work has yet to be done showing the proliferation of peroxisomes in cardiac tissue, but findings in other tissues is highly suggestive of the need for future research in this area.…”

Section: Mitochondrial Biogenesis and Dynamicsmentioning

confidence: 85%

Sex Hormone Regulation of Proteins Modulating Mitochondrial Metabolism, Dynamics and Inter-Organellar Cross Talk in Cardiovascular Disease

Lynch

Boyett

Smith

et al. 2021

Front. Cell Dev. Biol.

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Cardiovascular disease (CVD) is the leading cause of death in the U.S. and worldwide. Sex-related disparities have been identified in the presentation and incidence rate of CVD. Mitochondrial dysfunction plays a role in both the etiology and pathology of CVD. Recent work has suggested that the sex hormones play a role in regulating mitochondrial dynamics, metabolism, and cross talk with other organelles. Specifically, the female sex hormone, estrogen, has both a direct and an indirect role in regulating mitochondrial biogenesis via PGC-1α, dynamics through Opa1, Mfn1, Mfn2, and Drp1, as well as metabolism and redox signaling through the antioxidant response element. Furthermore, data suggests that testosterone is cardioprotective in males and may regulate mitochondrial biogenesis through PGC-1α and dynamics via Mfn1 and Drp1. These cell-signaling hubs are essential in maintaining mitochondrial integrity and cell viability, ultimately impacting CVD survival. PGC-1α also plays a crucial role in inter-organellar cross talk between the mitochondria and other organelles such as the peroxisome. This inter-organellar signaling is an avenue for ameliorating rampant ROS produced by dysregulated mitochondria and for regulating intrinsic apoptosis by modulating intracellular Ca2+ levels through interactions with the endoplasmic reticulum. There is a need for future research on the regulatory role of the sex hormones, particularly testosterone, and their cardioprotective effects. This review hopes to highlight the regulatory role of sex hormones on mitochondrial signaling and their function in the underlying disparities between men and women in CVD.

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“…Under such experimental conditions, peroxisomal localization of ADHAPR might be regulated by accelerating targeting of ADHAPR to peroxisomes and/or by suppressing ADHAPR degradation in peroxisomes. In this context, it is interesting that transcription of mRNAs encoding PMPs including Pex19p is acutely up-regulated in human skeletal muscle at 4 h post-supplementation of high fat meal ( Huang et al, 2019 ). Moreover, ADHARP is highly expressed in several tissues including liver, white adipocytes, and brain ( Lodhi et al, 2012 ), suggesting that acyl-DHAP pathway is involved in the synthesis of non-ether glycerophospholipids.…”

Section: Discussionmentioning

confidence: 99%

Distinct Functions of Acyl/Alkyl Dihydroxyacetonephosphate Reductase in Peroxisomes and Endoplasmic Reticulum

Honsho

Tanaka

Zoeller

et al. 2020

Front. Cell Dev. Biol.

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Plasmalogens are a subclass of ether glycerophospholipids characterized by a vinylether bond at the sn-1 position of the glycerol backbone. Plasmalogen biosynthesis is initiated in peroxisomes. At the third step of plasmalogen synthesis, alkyldihydroxyacetonephosphate (DHAP) is enzymatically reduced to 1-alkyl-sn-glycero-3phospate by acyl/alkyl DHAP reductase (ADHAPR), whose activity is found in both peroxisomes and microsomes. We herein show that knockdown of ADHAPR in HeLa cells reduced the synthesis of ethanolamine plasmalogen (PlsEtn), similar to the Chinese hamster ovary cell mutant FAA.K1B deficient in ADHAPR activity. Endogenous ADHAPR and ectopically expressed FLAG-tagged ADHAPR were localized to peroxisomes and endoplasmic reticulum (ER) as a type I integral membrane protein in HeLa cells. ADHAPR targets to peroxisomes via a Pex19p-dependent class I pathway. In addition, it is also inserted into the ER via the SRP-dependent mechanism. The ADHAPR mutant lacking the N-terminal domain preferentially targets to the ER, restoring the reduced level of PlsEtn synthesis in FAA.K1B cell. In contrast, the expression of full-length ADHAPR in the mutant cells elevates the synthesis of phosphatidylethanolamine, but not PlsEtn. Taken together, these results suggest that the third step of plasmalogen synthesis is mediated by ER-localized ADHAPR.

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Peroxisomal gene and protein expression increase in response to a high-lipid challenge in human skeletal muscle

Cited by 11 publications

References 37 publications

Combined effects of a ketogenic diet and exercise training alter mitochondrial and peroxisomal substrate oxidative capacity in skeletal muscle

Combined effects of a ketogenic diet and exercise training alter mitochondrial and peroxisomal substrate oxidative capacity in skeletal muscle

Sex Hormone Regulation of Proteins Modulating Mitochondrial Metabolism, Dynamics and Inter-Organellar Cross Talk in Cardiovascular Disease

Distinct Functions of Acyl/Alkyl Dihydroxyacetonephosphate Reductase in Peroxisomes and Endoplasmic Reticulum

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