Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC97310.15690/vramn973ENDOCRINOLOGY: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ЭНДОКРИНОЛОГИИTRANSCRIPTOMICS RESEARCH IN THE CLINICAL AND EXPERIMENTAL INVESTIGATION OF PATHOGENETIC MECHANISMS OF ALIMENTARY OBESITYРОЛЬ ТРАНСКРИПТОМИКИ В ИССЛЕДОВАНИИ ПАТОГЕНЕТИЧЕСКИХ МЕХАНИЗМОВ АЛИМЕНТАРНОГО ОЖИРЕНИЯ В КЛИНИКЕ И ЭКСПЕРИМЕНТЕhttps://orcid.org/0000-0002-3671-6508GmoshinskiI. V.ГмошинскийИван Всеволодович
Russian Federation

IvanV. Gmoshinski– PhD.

Moscow

Гмошинский Иван Всеволодович - Доктор биологических наук, ведущий научный сотрудник лаборатории пищевой токсикологии и оценки безопасности нанотехнологий.

109240, Москва, Устьинский пр-д, д. 2/14, тел.: +7 (495) 698-53-71, SPIN-код: 4501-9387

gmosh@ion.ruhttps://orcid.org/0000-0002-6543-7495ApryatinS. A.АпрятинСергей Алексеевич
Russian Federation

SergeyA. Apryatin– PhD.

Moscow

Апрятин Сергей Алексеевич - Кандидат биологических наук, старший научный сотрудник лаборатории метаболомного и протеомного анализа.

109240, Москва, Устьинский проезд, д. 2/14, тел.: +7 (495) 698-53-92, SPIN-код: 4250-2758

apryatin@mail.ruhttps://orcid.org/0000-0001-6061-0095SharafetdinovKh. Kh.ШарафетдиновХайдерь Хамзярович
Russian Federation

Khayder’ Kh. Sharafetdinov - MD, PhD, Professor.

Moscow

Шарафетдинов Хайдерь Хамзярович - Доктор медицинских наук, профессор, заведующий отделением обмена веществ Клиники лечебного питания.

115446, Москва, Каширское шоссе, д. 21, тел.: +7 (499) 794-35-16, SPIN-код: 1236-8210

sharafandr@mail.ruhttps://orcid.org/0000-0002-4968-4517NikitjukD. B.НикитюкДмитрий Борисович
Russian Federation

Dmitriy B. Nikityuk - MD, PhD, Professor.

Moscow

Никитюк Дмитрий Борисович - Доктор медицинских наук, профессор, член-корреспондент РАН, директор, заведующий лабораторией спортивной антропологии и нутрициологии.

109240, Москва, Устьинский проезд, д. 2/14, тел.: +7 (495) 698-53-60, SPIN-код: 1236-8210

dimitrynik@mail.ruhttps://orcid.org/0000-0002-4164-8992TutelyanV. A.ТутельянВиктор Александрович
Russian Federation

Victor A. Tutelyan - MD, PhD, Professor.

Moscow

Тутельян Виктор Александрович - доктор медицинских наук, профессор, академик РАН, заведующий лабораторией энзимологии питания, научный руководитель.

109240, Москва, Устьинский проезд, д. 2/14, тел.: +7 (495) 698-53-46, SPIN-код: 5789-3980

tutelyan@ion.ruFederal Research Centre of Nutrition, Biotechnology and Food SafetyФедеральный исследовательский центр питания, биотехнологии и безопасности пищи200720187331721802003201818062018Copyright ©; 2018, "Paediatrician" Publishers LLCCopyright ©; 2018, Издательство "Педиатръ"2018"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/973

The review considers the significant role of changes in the transcriptome of organs and tissues for studying the molecular mechanisms of obesity development. Modern methods of transcriptomics including technologies for quantitative RT-PCR and DNA microarrays provided a new approach to the search for sensitive molecular markers as obesity predictors Differential gene expression profiles are mostly organo- and tissue-specific for adipose tissue, liver, brain, and other organs and tissues; can significantly differ in animal in vivo models with genetically determined and dietary induced obesity. At the same time, coordinated regulation is registered in the organs and tissues of expression of extensive groups of genes associated with lipid, cholesterol, and carbohydrate metabolism, the synthesis and circulation of neurotransmitters of dopamine and serotonin, peptide hormones, cytokines which induce systemic inflammation. For systemic regulation mechanisms causing a concerted change in the transcription of tens and hundreds of genes in obesity, the adipokines effects should be pointed out, primarily leptin, as well as pro-inflammatory cytokines, the micro-RNA (miRs) system and central effects developing at NPY/AgRP+ and POMC/CART+ neurons of the arcuate nucleus of the hypothalamus. Results of transcriptomic studies can be used in preclinical trials of new drugs and methods of dietary correction of obesity in animal’s in vivo models, as well as in the search for clinical predictors and markers of metabolic abnormalities in patients with obesity receiving personalized therapy. The main problem of transcriptomic studies in in vivo models is incomplete consistency between the data obtained with full-transcriptional profiling and the results of quantitative RT-PCR expression of individual candidate genes, as well as metabolic and proteomic studies. The identification and elimination of the causes of such discrepancies can be one of the promising areas for improving transcriptomical research.

Рассматривается значение изменений в транскриптоме органов и тканей для изучения молекулярных механизмов развития алиментарного ожирения. Современные методы транскриптомики, включая технологии количественной ОТ-ПЦР и ДНК-микрочипов, позволили по-новому подойти к поиску чувствительных молекулярных маркеров ожирения. Профили дифференциальной экспрессии генов являются во многом органо- и тканеспецифичными для жировой ткани, печени, головного мозга и других органов и тканей, а также могут существенно различаться на in vivo моделях животных с генетически обусловленным и индуцированным рационом ожирением. Вместе с тем отмечается согласованная регуляция в органах и тканях экспрессии обширных групп генов, связанных с липидным, холестериновым и углеводным обменом, синтезом и циркуляцией нейромедиаторов дофамина и серотонина, пептидных гормонов, цитокинов, являющихся индукторами системного воспаления. В качестве системных регуляторных механизмов, вызывающих согласованное изменение в транскрипции десятков и сотен генов при ожирении, следует указать эффекты адипокинов, в первую очередь лептина, а также провоспалительных цитокинов, систему микроРНК (miRs) и центральные эффекты, реализуемые на уровне NPY/AgRP+ и POMC/CART+ нейронов дугообразного ядра гипоталамуса. Результаты транскриптомных исследований могут использоваться в доклинических испытаниях новых лекарственных средств и методов диетической коррекции ожирения на in vivo моделях, а также в поиске клинических предикторов и маркеров метаболических нарушений у больных ожирением, получающих персонализированную терапию. Основной проблемой транскриптомных исследований на in vivo моделях является неполная согласованность между данными, полученными при полнотранскриптомном профилировании, и результатами количественной полимеразной цепной реакции с обратной транскрипцией экспрессии отдельных кандидатных генов, а также метаболомных и протеомных исследований. Выявление и устранение причин таких расхождений может стать одним из перспективных направлений совершенствования транскриптомных исследований.

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