vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ21.053vavilov-3104Research ArticleГЕНЕТИКА ЖИВОТНЫХANIMAL GENETICSТранскрипционный фактор dFOXO регулирует экспрессию генов инсулинового сигнального каскада и содержание липидов при тепловом стрессе у Drosophila melanogasterThe transcription factor dFOXO controls the expression of insulin pathway genes and lipids content under heat stress in Drosophila melanogasterhttps://orcid.org/0000-0001-6136-6928ЕреминаМ. А.EreminaM. A.

Новосибирск

Novosibirsk

eremina@bionet.nsc.ruМеньшановП. Н.MenshanovP. N.

Новосибирск

Novosibirsk

ШишкинаО. Д.ShishkinaO. D.

Новосибирск

Novosibirsk

https://orcid.org/0000-0003-3272-1518ГрунтенкоН. Е.GruntenkoN. E.

Новосибирск

Novosibirsk

Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский государственный технический университетРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State Technical UniversityRussian Federation202109092021255465471Copyright © Еремина М.А., Меньшанов П.Н., Шишкина О.Д., Грунтенко Н.Е., 20212021Еремина М.А., Меньшанов П.Н., Шишкина О.Д., Грунтенко Н.Е.Eremina M.A., Menshanov P.N., Shishkina O.D., Gruntenko N.E.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/3104

Одним из основных элементов ответа организма на неблагоприятные условия является с нальный каскад инсулина/инсулиноподобных факторов роста (И/ИФР). Благодаря глубокой гомологии этого каскада и эволюционной консервативности его роли в регуляции углеводно-жирового метаболизма, возможно использование модельного объекта Drosophila melanogaster для изучения механизмов его функционирования. Для определения особенностей взаимодействия двух ключевых компонентов каскада И/ИФР у D. melanogaster – транскрипционного фактора dFOXO и инсулиноподобного пептида DILP6, «посредника» в передаче сигнала от dFOXO в жировом теле к инсулин-продуцирующим клеткам мозга (месту синтеза DILPs1–5), в условиях теплового стресса мы провели анализ экспрессии генов dilp6, dfoxo и гена инсулиноподобного рецептора (dInR) у самок линий, несущих гипоморфную мутацию dilp641 и гипофункциональную мутацию foxoBG01018. Обнаружено, что обе мутации не оказывали влияния на экспрессию dfoxo и ее повышение при кратковременном тепловом стрессе, однако нарушали ответ на стресс генов dilp6 и dInR. Для выявления роли обнаруженных нарушений в контроле метаболизма и метаболического поведения мы проанализировали влияние мутаций dilp641 и foxoBG01018 на содержание общих липидов и интенсивность капиллярного питания имаго в нормальных условиях и при кратковременном тепловом стрессе. Обе мутации приводили к усилению данных признаков в нормальных условиях и препятствовали снижению содержания общих липидов после стресса, наблюдаемому у контрольной линии. Интенсивность питания была повышена у мутантов в нормальных условиях и снижалась после кратковременного теплового стресса у всех изученных линий в течение первых суток наблюдения, а у линии dilp641 – в течение двух суток. Таким образом, можно заключить, что dFOXO принимает участие в регуляции как ответа сигнального каскада И/ИФР на тепловой стресс, так и вызываемых тепловым стрессом изменений в содержании липидов, причем эта регуляция опосредуется DILP6. В то же время метаболическое поведение имаго, по-видимому, регулируется dFOXO и DILP6 в нормальных условиях, но не при тепловом стрессе.

The insulin/insulin-like growth factor signaling (IIS) pathway is one of the key elements in an organism’s response to unfavourable conditions. The deep homology of this pathway and its evolutionary conservative role in controlling the carbohydrate and lipid metabolism make it possible to use Drosophila melanogaster for studying its functioning. To identify the properties of interaction of two key IIS pathway components under heat stress in D. melanogaster (the forkhead box O transcription factor (dFOXO) and insulin-like peptide 6 (DILP6), which intermediates the dFOXO signal sent from the fat body to the insulin-producing cells of the brain where DILPs1–5 are synthesized), we analysed the expression of the genes dilp6, dfoxo and insulin-like receptor gene (dInR) in females of strains carrying the hypomorphic mutation dilp641 and hypofunctional mutation foxoBG01018. We found that neither mutation influenced dfoxo expression and its uprise under short-term heat stress, but both of them disrupted the stress response of the dilp6 and dInR genes. To reveal the role of identified disruptions in metabolism control and feeding behaviour, we analysed the effect of the dilp641 and foxoBG01018 mutations on total lipids content and capillary feeding intensity in imago under normal conditions and under short-term heat stress. Both mutations caused an increase in these parameters under normal conditions and prevented decrease in total lipids content following heat stress observed in the control strain. In mutants, feeding intensity was increased under normal conditions; and decreased following short-term heat stress in all studied strains for the first 24 h of observation, and in dilp641 strain, for 48 h. Thus, we may conclude that dFOXO takes part in regulating the IIS pathway response to heat stress as well as the changes in lipids content caused by heat stress, and this regulation is mediated by DILP6. At the same time, the feeding behaviour of imago might be controlled by dFOXO and DILP6 under normal conditions, but not under heat stress.

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The authors declare that there are no conflicts of interest present.