Fatty acids are essential components of biological membranes, important for the maintenance of cellular structures, especially in organisms with complex life cycles like protozoan parasites. Apicomplexans are obligate parasites responsible for various deadly diseases of humans and livestock. We analyzed the fatty acids produced by the closest phototrophic relatives of parasitic apicomplexans, the chromerids Chromera velia and Vitrella brassicaformis, and investigated the genes coding for enzymes involved in fatty acids biosynthesis in chromerids, in comparison to their parasitic relatives. Based on evidence from genomic and metabolomic data, we propose a model of fatty acid synthesis in chromerids: the plastid-localized FAS-II pathway is responsible for the de novo synthesis of fatty acids reaching the maximum length of 18 carbon units. Short saturated fatty acids (C14:0-C18:0) originate from the plastid are then elongated and desaturated in the cytosol and the endoplasmic reticulum. We identified giant FAS I-like multi-modular enzymes in both chromerids, which seem to be involved in polyketide synthesis and fatty acid elongation. This full-scale description of the biosynthesis of fatty acids and their derivatives provides important insights into the reductive evolutionary transition of a phototropic algal ancestor to obligate parasites.
- MeSH
- Apicomplexa klasifikace genetika metabolismus MeSH
- biosyntetické dráhy genetika MeSH
- desaturasy mastných kyselin klasifikace genetika metabolismus MeSH
- druhová specificita MeSH
- elongasy mastných kyselin klasifikace genetika metabolismus MeSH
- fylogeneze MeSH
- lidé MeSH
- mastné kyseliny biosyntéza MeSH
- molekulární evoluce MeSH
- protozoální infekce parazitologie MeSH
- protozoální proteiny klasifikace genetika metabolismus MeSH
- synthasa mastných kyselin, typ 2 klasifikace genetika metabolismus MeSH
- synthasa mastných kyselin, typ I klasifikace genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: Crosstalk between adipocytes and local neurons may be an important regulatory mechanism to control energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) expands sympathetic neurons within white adipose tissue (WAT) and stimulates the appearance of "beige" adipocytes. Here we tested whether WAT DNL activity can also influence neuronal regulation and thermogenesis in brown adipose tissue (BAT). METHODS AND RESULTS: Induced deletion of FASN in all adipocytes in mature mice (iAdFASNKO) enhanced sympathetic innervation and neuronal activity as well as UCP1 expression in both WAT and BAT. This increased sympathetic innervation could be observed at both 22 °C and 30 °C, indicating it is not a response to heat loss but rather adipocyte signaling. In contrast, selective ablation of FASN in brown adipocytes of mice (iUCP1FASNKO) failed to modulate sympathetic innervation and the thermogenic program in BAT. Surprisingly, DNL in brown adipocytes was also dispensable in maintaining euthermia when UCP1FASNKO mice were cold-exposed. CONCLUSION: These results indicate that DNL in white adipocytes influences long distance signaling to BAT, which can modify BAT sympathetic innervation and expression of genes involved in thermogenesis.
- MeSH
- adipozita MeSH
- béžové tukové buňky metabolismus MeSH
- bílá tuková tkáň metabolismus MeSH
- bílé tukové buňky metabolismus MeSH
- hnědá tuková tkáň metabolismus MeSH
- hnědé tukové buňky metabolismus MeSH
- lipogeneze MeSH
- myši MeSH
- neurony metabolismus MeSH
- obezita metabolismus MeSH
- signální transdukce MeSH
- syntázy mastných kyselin MeSH
- synthasa mastných kyselin, typ I genetika metabolismus MeSH
- termogeneze MeSH
- termoregulace MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, N.I.H., Extramural MeSH
