Postnatal induction of muscle fatty acid oxidation in mice differing in propensity to obesity: a role of pyruvate dehydrogenase

Buresova, Jana; Janovská, Petra; Kuda, Ondřej; Křížová, Jana; Stelt, Inge Romijnders van der; Keijer, Jaap; Hansı́ková, Hana; Rossmeisl, Martin; Kopecký, Jan

doi:10.1038/s41366-018-0281-0

Cited by 7 publications

(6 citation statements)

References 54 publications

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“…Contact sites between mitochondria and lipid droplets (i.e., membranes within 30 nm 36 ) followed a similar pattern with a nearly ten-fold loss in lipid droplet contact site abundance per mitochondrion across postnatal development in the oxidative muscles and a complete loss of contact sites in mature glycolytic muscle where no lipid droplets were found ( Figure 2f ). These data suggest that physical interactions between mitochondria and lipid droplets, which facilitate direct transfer of molecules between them, may be directly related to the metabolic fuel preferences of the skeletal muscle cell, as neonatal muscles are known to rely more heavily on fatty acids compared to adult muscles 37 , while glycolytic muscles rely more on carbohydrate fuel sources relative to oxidative muscles 38 .…”

Section: Resultsmentioning

confidence: 94%

“…The copyright holder for this preprint this version posted June 17, 2021. ; https://doi.org/10.1101/2021.06.16.448433 doi: bioRxiv preprint direct transfer of molecules between them, may be directly related to the metabolic fuel preferences of the skeletal muscle cell, as neonatal muscles are known to rely more heavily on fatty acids compared to adult muscles 37 , while glycolytic muscles rely more on carbohydrate fuel sources relative to oxidative muscles 38 .…”

Section: Mitochondria-lipid Droplet (Ld) Contact Sites Decrease In Frequency Across Postnatal Developmentmentioning

confidence: 99%

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Reorganization of the Mitochondria-Organelle Interactome during Postnatal Development in Skeletal Muscle

Kim

Lindberg

Bleck

2021

Preprint

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Cellular development requires the integrated assembly of intracellular structures into functionally specialized regions supporting overall cellular performance. However, it remains unclear how coordination of organelle interactions contributes to development of functional specificity across cell types. Here, we utilize a subcellular connectomics approach to define the cell-scale reorganization of the mitochondria-organelle interactome across postnatal development in skeletal muscle. We show that while mitochondrial networks are disorganized and loosely associated with the contractile apparatus at birth, contact sites among mitochondria, lipid droplets, and the sarcoplasmic reticulum are highly abundant in neonatal muscles. The maturation process is characterized by a transition to highly organized mitochondrial networks wrapped tightly around the muscle sarcomere but also to less frequent interactions with both lipid droplets and the sarcoplasmic reticulum. These data demonstrate a developmental redesign reflecting a functional shift from muscle cell assembly supported by inter-organelle communication toward a muscle fiber highly specialized for contractile function.

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Section: Resultsmentioning

confidence: 94%

Section: Mitochondria-lipid Droplet (Ld) Contact Sites Decrease In Frequency Across Postnatal Developmentmentioning

confidence: 99%

Reorganization of the Mitochondria-Organelle Interactome during Postnatal Development in Skeletal Muscle

Kim

Lindberg

Bleck

2021

Preprint

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“…For the source data, see Figure 1 and Tables S1, 1, and 2. ACE/ARB inhibitors, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers; BNP, natriuretic peptides B; BMI, body mass index; BW, body weight; NPRC, natriuretic peptide receptor C included (i) PPARα, which acts both as a sensor for fatty acids and ligand-activated transcription factor enhancing lipid catabolism, (ii) PPARγ, and its target PGC-1α inducing mitochondrial biogenesis, 27 (iii) PDK4, which limits glucose oxidation by inhibiting pyruvate dehydrogenase and thus supports β-oxidation, 28 and (iv) ACSL1 and ACADL, which are engaged in mitochondrial β-oxidation of fatty acids. Expression of all these genes tended to be up-regulated in cachexia ( Figure 1C).…”

Section: Clinical Characteristicsmentioning

confidence: 99%

Dysregulation of epicardial adipose tissue in cachexia due to heart failure: the role of natriuretic peptides and cardiolipin

Janovská

Melenovský

Svobodová

et al. 2020

J cachexia sarcopenia muscle

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Background Cachexia worsens long-term prognosis of patients with heart failure (HF). Effective treatment of cachexia is missing. We seek to characterize mechanisms of cachexia in adipose tissue, which could serve as novel targets for the treatment. Methods The study was conducted in advanced HF patients (n = 52; 83% male patients) undergoing heart transplantation. Patients with ≥7.5% non-intentional body weight (BW) loss during the last 6 months were rated cachectic. Clinical characteristics and circulating markers were compared between cachectic (n = 17) and the remaining, BW-stable patients. In epicardial adipose tissue (EAT), expression of selected genes was evaluated, and a combined metabolomic/lipidomic analysis was performed to assess (i) the role of adipose tissue metabolism in the development of cachexia and (ii) potential impact of cachexia-associated changes on EAT-myocardium environment. Results Cachectic vs. BW-stable patients had higher plasma levels of natriuretic peptide B (BNP; 2007 ± 1229 vs. 1411 ± 1272 pg/mL; P = 0.010) and lower EAT thickness (2.1 ± 0.8 vs. 2.9 ± 1.4 mm; P = 0.010), and they were treated with 2.5-fold lower dose of both β-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACE/ARB-inhibitors). The overall pattern of EAT gene expression suggested simultaneous activation of lipolysis and lipogenesis in cachexia. Lower ratio between expression levels of natriuretic peptide receptors C and A was observed in cachectic vs. BW-stable patients (0.47 vs. 1.30), supporting activation of EAT lipolysis by natriuretic peptides. Fundamental differences in metabolome/lipidome between BW-stable and cachectic patients were found. Mitochondrial phospholipid cardiolipin (CL), specifically the least abundant CL 70:6 species (containing C16:1, C18:1, and C18:2 acyls), was the most discriminating analyte (partial least squares discriminant analysis; variable importance in projection score = 4). Its EAT levels were higher in cachectic as compared with BW-stable patients and correlated with the degree of BW loss during the last 6 months (r = À0.94; P = 0.036). Conclusions Our results suggest that (i) BNP signalling contributes to changes in EAT metabolism in cardiac cachexia and (ii) maintenance of stable BW and 'healthy' EAT-myocardium microenvironment depends on the ability to tolerate higher doses of both ACE/ARB inhibitors and β-adrenergic blockers. In line with preclinical studies, we show for the first time in humans the association of cachexia with increased adipose tissue levels of CL. Specifically, CL 70:6 could precipitate wasting of adipose tissue, and thus, it could represent a therapeutic target to ameliorate cachexia.

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“…Both TZDs promoted lipolysis and FA re-esterification, in association with the elevation of mitochondrial β-oxidation. The Regarding FA oxidation ( Figure 8F), expression of the gene for PDK4 (Pdk4), which limits glucose oxidation by inhibiting pyruvate dehydrogenase and thus supports β-oxidation [49], was downregulated by HF diet. It was increased by both TZDs, with a stronger effect of MSDC-0602K, and it was insensitive to Omega-3.…”

Section: Gene Expression In Adipose Tissuementioning

confidence: 99%

Additive Effects of Omega-3 Fatty Acids and Thiazolidinediones in Mice Fed a High-Fat Diet: Triacylglycerol/Fatty Acid Cycling in Adipose Tissue

et al. 2020

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Long-chain n-3 polyunsaturated fatty acids (Omega-3) and anti-diabetic drugs thiazolidinediones (TZDs) exhibit additive effects in counteraction of dietary obesity and associated metabolic dysfunctions in mice. The underlying mechanisms need to be clarified. Here, we aimed to learn whether the futile cycle based on the hydrolysis of triacylglycerol and re-esterification of fatty acids (TAG/FA cycling) in white adipose tissue (WAT) could be involved. We compared Omega-3 (30 mg/g diet) and two different TZDs—pioglitazone (50 mg/g diet) and a second-generation TZD, MSDC-0602K (330 mg/g diet)—regarding their effects in C57BL/6N mice fed an obesogenic high-fat (HF) diet for 8 weeks. The diet was supplemented or not by the tested compound alone or with the two TZDs combined individually with Omega-3. Activity of TAG/FA cycle in WAT was suppressed by the obesogenic HF diet. Additive effects in partial rescue of TAG/FA cycling in WAT were observed with both combined interventions, with a stronger effect of Omega-3 and MSDC-0602K. Our results (i) supported the role of TAG/FA cycling in WAT in the beneficial additive effects of Omega-3 and TZDs on metabolism of diet-induced obese mice, and (ii) showed differential modulation of WAT gene expression and metabolism by the two TZDs, depending also on Omega-3.

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Postnatal induction of muscle fatty acid oxidation in mice differing in propensity to obesity: a role of pyruvate dehydrogenase

Cited by 7 publications

References 54 publications

Reorganization of the Mitochondria-Organelle Interactome during Postnatal Development in Skeletal Muscle

Reorganization of the Mitochondria-Organelle Interactome during Postnatal Development in Skeletal Muscle

Dysregulation of epicardial adipose tissue in cachexia due to heart failure: the role of natriuretic peptides and cardiolipin

Additive Effects of Omega-3 Fatty Acids and Thiazolidinediones in Mice Fed a High-Fat Diet: Triacylglycerol/Fatty Acid Cycling in Adipose Tissue

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