Dataset Information

Decreased mitochondrial-related gene expression in adipose tissue after acute sprint exercise in humans

ABSTRACT: The aim was to examine the acute effects of sprint exercise (SIT) on global gene expression in subcutaneous adipose tissue (AT) in healthy subjects to improve the understanding of how SIT may contribute to the maintenance of a healthy body weight. An SIT-induced upregulation of genes related to mitochondrial and fat metabolism was hypothesized. A total of 15 subjects performed three 30-s all-out sprints (SIT). Samples from AT, skeletal muscle (SM) and blood (brachial artery and a superficial subcutaneous abdominal vein) were obtained, up to 15 min after the last sprint. Purines such as hypoxanthine, xanthine or uric acid, sources of oxidative stress, increased markedly by SIT in both the artery and the abdominal vein. Purines also increased in AT and SM tissue. In response to SIT, a decreased signaling was predicted from the differential gene expression (z-score < -2 and -log(p-value) > 4) for mitochondrial related pathways such as oxidative phosphorylation, electron transport, ATP synthesis and heat production by uncoupling, mitochondrial fatty acid beta oxidation. Contrary to the hypothesis, a downregulation of various gene sets related to oxidative metabolism was shown after SIT. This could counteract possible negative effects of SIT-induced oxidative stress by an early stage “shutdown” of the mitochondria.

ORGANISM(S): Homo sapiens

PROVIDER: GSE267959 | GEO | 2024/10/30

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Methods for studying mitochondrial adaptations in skeletal muscle have mostly used whole-muscle samples, where results may be confounded by the presence of a mixture of type I and II skeletal muscle fibres. In this project, we utilised the latest Mass spectrometry (MS) techniques to provide new insights into mitochondrial adaptations in type I and II fibres in response to two different types of training – moderate-intensity-continuous training (MICT) and sprint-interval training (SIT). An 8-week training intervention was undertaken by 23 men who performed either MICT or SIT. Single muscle fibres from skeletal muscle biopsies were collected at rest, before and after the 8 weeks of training, and pooled for subsequent MS analysis. A proteomic workflow was applied that permitted a three-tiered comparison and quantification of mitochondrial proteins in different fibre types. Our protocol includes tandem mass tag labelling for increased identification of low-abundant proteins. We quantified more than 45% of known mitochondrial proteins in skeletal muscle. When comparing type I to type II fibres,24 mitochondrial proteins were differentially expressed following MICT and 10 following SIT. These altered proteins were associated with known cellular pathways within the mitochondria, including oxidative phosphorylation, the TCA cycle and fatty acid oxidation. There were distinct trends for fibre-type-specific protein responses to different types of exercise training. Following MICT proteins mostly increased in abundance in type I fibres, without analogous changes observed following SIT. This greater upregulation of mitochondrial proteins observed following MICT, suggests exercise volume is a powerful stimulus for mitochondrial adaptations. This upregulation mostly seen in type I fibres is consistent with the predominate recruitment of this fibre type with MICT. When normalised to mitochondrial content further evidence to fibre-specific non-stoichiometrically induced increases in the expression of fatty acid mitochondrial proteins is presented, highlighting mitochondria as a pivotal subcellular site in facilitating substrate utilisation to increase ATP production in type I fibres. Conversely, the research suggests very high-intensity exercise training altered the systematic biogenesis of oxidative phosphorylation (OXPHOS) components, in particular complex IV subunits of the OXPHOS pathway. These results question the existing knowledge of fibre-type-specific changes to mitochondrial proteins in response to exercise training and provide a valuable contribution to understanding the mechanisms by which exercise helps to improve health and prevent disease.

Project description:Background and objective: Combination antiretroviral therapy (cART) is associated with lipodystrophy i.e. loss of subcutaneous adipose tissue in abdomen, limbs and face and its accumulation intra-abdominally. No fat is lost dorsocervically and it can even accumulates in this region (“buffalo hump”). It is unknown how preserved dorsocervical fat differs from abdominal subcutaneous fat in HIV-1-infected cART-treated patients with (cART+LD+) and without (cART+LD-) lipodystrophy. Results: Albeit dorsocervical adipose tissue in cART+LD+ seems spared from lipoatrophy, its mitochondrial DNA (mtDNA, copies/cell) content was significantly lower (by 62%) than that of the corresponding tissue in cART+LD-. Expression of CD68 mRNA, a marker of macrophages, and numerous inflammatory genes in microarray were significantly lower in dorsocervical vs. abdominal subcutaneous adipose tissue. Genes with the greatest difference in expression between the two depots were those involved in regulation of transcription and regionalization (homeobox genes), irrespective of lipodystrophy status. There was negligible mRNA expression of uncoupling protein 1, a gene characteristic of brown adipose tissue, in either depot. Conclusions: As mtDNA is depleted even in the non-atrophic dorsocervical adipose tissue, it is unlikely that the cause of lipoatrophy is loss of mtDNA. Dorsocervical adipose tissue is less inflamed than lipoatrophic adipose tissue. It does not resemble brown adipose tissue. The greatest difference in gene expression between dorsocervical and abdominal s.c. adipose tissue is in expression of homeobox genes. We used histology, microarray, polymerase chain reaction and magnetic resonance imaging to compare dorsocervical and abdominal subcutaneous adipose tissue in cART+LD+ (n=21) and cART+LD- (n=11). The study consists of 17 patients on antiretroviral treatment who have developed lipodystrophy and 11 patients that are on similar treatment but have not developped lipodystrophy. All patients are HIV+ and have 2 adipose tissue samples taken from them (dorsocervical+abdominal).

Project description:Recent studies on mouse and human skeletal muscle (SM) demonstrated the important link between mitochondrial function and the cellular metabolic adaptation. To identify key compensatory molecular mechanisms in response to chronic mitochondrial distress, we analyzed mice with ectopic SM respiratory uncoupling in uncoupling protein 1 transgenic (UCP1-TG) mice as model of muscle-specific compromised mitochondrial function. Here we describe a detailed metabolic reprogramming profile associated with mitochondrial perturbations in SM, triggering an increased protein turnover and amino acid metabolism with induced biosynthetic serine/1-carbon/glycine pathway and the longevity-promoting polyamine spermidine as well as the trans-sulfuration pathway. This is related to an induction of NADPH-generating pathways and glutathione metabolism as an adaptive mitohormetic response and defense against increased oxidative stress. Strikingly, consistent muscle retrograde signaling profiles were observed in acute stress states such as muscle cell starvation and lipid overload, muscle regeneration, and heart muscle inflammation, but not in response to exercise. We provide conclusive evidence for a key compensatory stress-signaling network that preserves cellular function, oxidative stress tolerance, and survival during conditions of increased SM mitochondrial distress, a metabolic reprogramming profile so far only demonstrated for cancer cells and heart muscle.-Ost, M., Keipert, S., van Schothorst, E. M., Donner, V., van der Stelt, I., Kipp, A. P., Petzke, K.-J., Jove, M., Pamplona, R., Portero-Otin, M., Keijer, J., and Klaus, S. Muscle mitohormesis promotes cellular survival via serine/glycine pathway flux. Control C57BL/6J wildtype male mice, aged 12 weeks, are compared to UCP1 transgene littermates fed purified low fat diet (BIOCLAIMS, Hoevenaars et al., Genes and Nutrition 2012) for 12 weeks . At the end, mice were sacrificed, gastrocnemius skeletal muscle was immediately dissected and snap frozen in liquid nitrogen. Total RNA was isolated, quantified and qualified, and subsequently used for global gene expression profiling using Agilent 8x60K microarrays. In total, 6 arrays of individual WT and 7 arrays of individual UCP1-TG samples were normalized, together with samples from the complete SUPERSERIES.

Dataset Information

Decreased mitochondrial-related gene expression in adipose tissue after acute sprint exercise in humans

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets