Brown adipose tissue (BAT) plays an important role in lipid and glucose metabolism in rodents and possibly also in humans. Identification of genes responsible for BAT function would shed light on underlying pathophysiological mechanisms of metabolic disturbances. Recent linkage analysis in the BXH/HXB recombinant inbred (RI) strains, derived from Brown Norway (BN) and spontaneously hypertensive rats (SHR), identified two closely linked quantitative trait loci (QTL) associated with glucose oxidation and glucose incorporation into BAT lipids in the vicinity of Wars2 (tryptophanyl tRNA synthetase 2 (mitochondrial)) gene on chromosome 2. The SHR harbors L53F WARS2 protein variant that was associated with reduced angiogenesis and Wars2 thus represents a prominent positional candidate gene. In the current study, we validated this candidate as a quantitative trait gene (QTG) using transgenic rescue experiment. SHR-Wars2 transgenic rats with wild type Wars2 gene when compared to SHR, showed more efficient mitochondrial proteosynthesis and increased mitochondrial respiration, which was associated with increased glucose oxidation and incorporation into BAT lipids, and with reduced weight of visceral fat. Correlation analyses in RI strains showed that increased activity of BAT was associated with amelioration of insulin resistance in muscle and white adipose tissue. In summary, these results demonstrate important role of Wars2 gene in regulating BAT function and consequently lipid and glucose metabolism.
- MeSH
- energetický metabolismus * genetika MeSH
- fenotyp MeSH
- genetická predispozice k nemoci MeSH
- genetické asociační studie MeSH
- glukosa metabolismus MeSH
- hnědá tuková tkáň metabolismus patologie MeSH
- kultivované buňky MeSH
- lokus kvantitativního znaku MeSH
- metabolismus lipidů MeSH
- mitochondrie metabolismus MeSH
- mutace * MeSH
- nitrobřišní tuk metabolismus patofyziologie MeSH
- obezita genetika metabolismus patofyziologie MeSH
- potkani inbrední SHR MeSH
- tryptofan-tRNA-ligasa genetika MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- dyslipidemie komplikace metabolismus MeSH
- energetický metabolismus fyziologie imunologie MeSH
- financování organizované MeSH
- hnědá tuková tkáň metabolismus patologie MeSH
- inzulinová rezistence * genetika imunologie MeSH
- lidé MeSH
- metabolismus lipidů fyziologie genetika MeSH
- obezita komplikace metabolismus MeSH
- rizikové faktory * MeSH
- stárnutí * fyziologie metabolismus patologie MeSH
- statistika jako téma MeSH
- tělesná hmotnost fyziologie genetika imunologie MeSH
- triglyceridy izolace a purifikace metabolismus škodlivé účinky MeSH
- Check Tag
- lidé MeSH
While metabolic syndrome is often associated with obesity, 25% of humans suffering from it are not obese and the effect of physical activity remains unclear in such cases. Therefore, we used hereditary hypertriaclyglycerolemic (HHTg) rats as a unique model for studying the effect of spontaneous physical activity [voluntary running (VR)] on metabolic syndrome-related disorders, such as dyslipidemia, in non-obese subjects. Adult HHTg males were fed standard (CD) or high-sucrose (HSD) diets ad libitum for four weeks. Within both dietary groups, some of the rats had free access to a running wheel (CD+VR, HSD+VR), whereas the controls (CD, HSD) had no possibility of extra physical activity. At the end of the four weeks, we measured the effects of VR on various metabolic syndrome-associated parameters: (i) biochemical parameters, (ii) the content and composition of triacylglycerols (TAG), diacylglycerols (DAG), ceramides and membrane phospholipids, and (iii) substrate utilization in brown adipose tissue. In both dietary groups, VR led to various positive effects: reduced epididymal and perirenal fat depots; increased epididymal adipose tissue lipolysis; decreased amounts of serum TAG, non-esterified fatty acids and insulin; a higher insulin sensitivity index. While tissue ceramide content was not affected, decreased TAG accumulation resulted in reduced and modified liver, heart and skeletal muscle DAG. VR also had a beneficial effect on muscle membrane phospholipid composition. In addition, compared with the CD group, the CD+VR rats exhibited increased fatty acid oxidation and protein content in brown adipose tissue. Our results confirm that physical activity in a non-obese model of severe dyslipidemia has many beneficial effects and can even counteract the negative effects of sucrose consumption. Furthermore, they suggest that the mechanism by which these effects are modulated involves a combination of several positive changes in lipid metabolism.
- MeSH
- běh fyziologie MeSH
- bílá tuková tkáň patologie MeSH
- buněčná membrána metabolismus MeSH
- ceramidy metabolismus MeSH
- fosfolipidy metabolismus MeSH
- hnědá tuková tkáň metabolismus patologie MeSH
- hypertriglyceridemie krev MeSH
- kosterní svaly metabolismus patologie MeSH
- krysa rodu rattus MeSH
- metabolický syndrom krev MeSH
- metabolismus lipidů * MeSH
- oxidační stres MeSH
- svalové buňky metabolismus MeSH
- triglyceridy metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
