Aleksandra Pyrkowska

Endurance training-induced accumulation of muscle triglycerides is coupled to upregulation of stearoyl-CoA desaturase 1.

Stearoyl-CoA desaturase (SCD), a rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids, has recently been shown to be a critical control point in regulation of liver and skeletal muscle metabolism. Herein, we demonstrate that endurance training significantly increases both SCD1 mRNA and protein levels in the soleus muscle, whereas it does not affect SCD1 expression in the EDL muscle and liver. Desaturation index (18:1Δ9/18:0 ratio), an indirect indicator of SCD1 activity, was also significantly higher (3.6-fold) in soleus of trained rats compared with untrained animals. Consistent with greater SCD1 expression/activity, the contents of free fatty acids, diacylglycerol, and triglyceride were elevated in soleus of trained rats. However, training did not affect lipid concentration in EDL and liver. Additionally, endurance training activated the AMP-activated protein kinase pathway as well as increased peroxisome proliferator-activated receptor (PPAR)-δ and PPARα gene expression and activity in soleus and liver. Increased lipid accumulation in soleus was coupled with elevated protein levels of fatty acid synthase, mRNA levels of diacylglycerol acyltransferase and glycerol-3-phosphate transferase, as well as increased levels of proteins involved in fatty acid transport (fatty acid translocase/CD36, fatty acid transport protein 1). Interestingly, sterol regulatory element-binding protein (SREBP)-1c expression and SREBP-1 protein levels were not affected by exercise training. Together, the obtained data suggest that SCD1 upregulation plays an important role in adaptation of oxidative muscle to endurance training.

Expression of lipogenic genes is upregulated in the heart with exercise training-induced but not pressure overload-induced left ventricular hypertrophy

Cardiac hypertrophy is accompanied by molecular remodeling that affects different cellular pathways, including fatty acid (FA) utilization. In the present study, we show that cardiac lipid metabolism is differentially regulated in response to physiological (endurance training) and pathological [abdominal aortic banding (AAB)] hypertrophic stimuli. Physiological hypertrophy was accompanied by an increased expression of lipogenic genes and the activation of sterol regulatory element-binding protein-1c and Akt signaling. Additionally, FA oxidation pathways regulated by AMP-activated protein kinase (AMPK) and peroxisome proliferator activated receptor-α (PPARα) were induced in trained hearts. Cardiac lipid content was not changed by physiological stimulation, underlining balanced lipid utilization in the trained heart. Moreover, pathological hypertrophy induced the AMPK-regulated oxidative pathway, whereas PPARα and expression of its downstream targets, i.e., acyl-CoA oxidase and carnitine palmitoyltransferase I, were not affected by AAB. In contrast, pathological hypertrophy leads to cardiac triglyceride (TG) and diacylglycerol (DAG) accumulation, although the expression of lipogenic genes and the levels of FA transport proteins (CD36 and FATP) were not changed or reduced compared with the sham group. A possible explanation for this phenomenon is a decrease in lipolysis, as evidenced by the increased content of adipose triglyceride lipase inhibitor G0S2, the increased phosphorylation of hormone-sensitive lipase at Ser(565), and the decreased protein levels of DAG lipase that attenuate TG and DAG contents. The increased TG and DAG accumulation observed in AAB-induced hypertrophy might have lipotoxic effects, thereby predisposing to cardiomyopathy and heart failure in the future.

Increased availability of endogenous and dietary oleic acid contributes to the upregulation of cardiac fatty acid oxidation.

In the present study, we tested the hypothesis that cardiac substrate utilization is affected by oleic acid originating from the endogenous conversion of stearate by stearoyl-CoA desaturase and from the diet. Here, we show that the cardiac oleate content is increased in tristearate (TS)- and trioleate (TO)-fed rats when compared with chow-fed rats. TS or TO feeding increases mitochondrial fatty acid oxidation via activation of expression of the oxidative genes, activation of the AMP-activated protein kinase pathway, and a decrease in glucose uptake. These results suggest that oleic acid, both dietary and de novo synthesized, affects substrate utilization in the heart. Furthermore, our data show that the endogenous synthesis of oleate in the heart can compensate for a deficiency of this fatty acid in the diet.

Monounsaturated fatty acids are required for membrane translocation of protein kinase C-theta induced by lipid overload in skeletal muscle.

Abstract Protein kinase C (PKC) activation induced by diacylglycerols (DAGs) is one of the sequels of the dysregulation of intramuscular lipid metabolism and is thought to play an important role in the development of insulin resistance (IR). We tested the hypothesis that DAGs with different acyl chains have different biological effects and that DAG species enriched in monounsaturated fatty acids (MUFA) act as better activators of PKC. The experiments were performed in vitro on C2C12 myotubes treated with palmitate (16:0), stearate (18:0) or oleate (18:1) and in vivo on the skeletal muscles of rats fed high-fat (HF), high-tristearin (TS) or high-triolein (TO) diets. To define the importance of endogenously synthesized MUFA on DAG-induced PKCθ activation, we performed experiments on stearoyl-CoA desaturase 1 knockout mice (SCD1-/-) as well. The results show that the content of total DAGs and the levels of saturated DAG species are significantly increased in both insulin-resistant (16:0, HF and TO) and highly insulin-sensitive (18:0 and TS) groups. An increase in MUFA-containing DAGs levels was most constantly related to increase in PKCθ membrane translocation and IR. In the muscles of MUFA-deficient SCD1-/- mice, the DAG content and the induction of PKCθ translocation by the HF diet were significantly reduced. Collectively, our data from both the cell and animal experiments show that DAGs composed of 16:1 and/or 18:1, rather than the levels of total or saturated DAGs, are related to PKCθ membrane translocation. Moreover, our results show that the availability of dietary MUFA and/or the activity of endogenous desaturases play an important role in muscle DAG accumulation.

Fatty acid profile and influence of oxythiamine on fatty acid content in Malassezia pachydermatis, Candida albicans and Saccharomyces cerevisiae.

Malassezia pachydermatis and Candida albicans are fungi involved in the skin diseases and systemic infections. The therapy of such infections is difficult due to relapses and problems with pathogen identification. In our study, we compare the fatty acids profile of M. pachydermatis, C. albicans and S. cerevisiae to identify diagnostic markers and to investigate the effect of oxythiamine (OT) on the lipid composition of these species. Total fatty acid content is threefold higher in C. albicans and M. pachydermatis compared with S. cerevisiae. These two species have also increased level of polyunsaturated fatty acids (PUFA) and decreased content of monounsaturated fatty acids (MUFA). We noted differences in the content of longer chain (>18) fatty acids between studied species (for example a lack of 20 : 1 in S. cerevisiae and 22 : 0 in M. pachydermatis and C. albicans). OT reduces total fatty acids content in M. pachydermatis by 50%. In S. cerevisiae, OT increased PUFA whereas it decreased MUFA content. In C. albicans, OT decreased PUFA and increased MUFA and SFA content. The results show that the MUFA to PUFA ratio and the fatty acid profile could be useful diagnostic tests to distinguish C. albicans, M. pachydermatis and S. cerevisiae, and OT affected the lipid metabolism of the investigated species, especially M. pachydermatis.

Comparison of lipid profiles of Malassezia pachydermatis strains isolated from dogs with otitis externa and without clinical symptoms of disease

Malassezia pachydermatis can cause infections of the skin and mucous membranes, especially in animals. It becomes a problem also in medicine. It is considered that metabolic disorders as well as hormonal and immunological status of the host promote diseases caused by M. pachydermatis. Here we consider whether specific features of fungi could also favour infections. We checked whether there are differences in lipid profiles between strains obtained from dogs with otitis externa and strains obtained from healthy dogs. Lipid profiles were determined using thin layer chromatography and gas chromatography–mass spectrometry. All analyses were carried out on 32 strains derived from dogs with otitis externa and 31 strains isolated from dogs without symptoms of disease. The results show that strains isolated from dogs without symptoms of otitis externa are characterised by a higher content of fatty acids. They contain significantly more behenic and lignoceric acids on medium without addition of lipids, and more oleic acid and total monounsaturated fatty acids on medium with lipids supplementation. These strains have also a higher content of esters of ergosterol and triglycerides. Data obtained show differences which may be specific features of M. pachydermatis‐specific strains related to the ability of infection, which could be not directly related of the host condition.