@васьвась я потратил часа 4 на внимательнейшее изучение всех этих данных на днях. Т.е. прочитал все свежее, и далее, по источникам вглубь, с уходом в бока гистологические и т.п.
Нет, нет никаких доказательств. А цитаты из пересказов с спид.центра… немного не смешно. Читайте источники. Вот только с ними проблемы, абстракт только есть по данной работе да слайдики. Впрочем, в любом случае, если 2 недели на 2,5 обезьянах это для кого-то повод для выводов – ну, это уже другая история.
PS3/4
Integrase inhibitors dolutegravir and raltegravir exert proadipogenic and profibrotic effects and induce insulin resistance in adipose tissue and adipocytes
J Gorwood1, C Bourgeois2, V Pourcher3, F Charlotte3, G Pourcher4, M Mantecon1, C Rose1, R Morichon1, R Le Grand2, C Katlama3,5, B Fève1,6, O Lambotte2,7, J Capeau1, V Béréziat1, C Lagathu1
1Sorbonne Universté INSERM UMRS 938 Saint‐Antoine research center, Paris, France 2CEA, Université Paris Sud, Inserm U1184, ImVA, IDMIT, Fontenay‐aux‐Roses, France 3AP‐HP, Sorbonne Université, Hôpital Pitié‐Salpêtrière, Service de maladies infectieuses et tropicales, INSERM U1136, Institut Pierre Louis d’épidémiologie et de Santé publique et d’Anatomo‐Pathologie, Paris, France 4Institut Mutualiste Montsouris, Service de Chirurgie Digestive, Paris, France 5Sorbonne Université, Inserm, Institut Pierre Louis d’épidémiologie et de Santé Publique, Paris, France 6AP‐HP, Hôpital Saint‐Antoine, Service d’endocrinologie, Paris, France 7APHP, Hôpital Bicêtre, Service de Médecine Interne et Immunologie Clinique, Kremlin‐Bicêtre, France
Purpose: There is growing evidence that integrase inhibitors (INSTI) dolutegravir and raltegravir promote peripheral and central adipose tissue/weight gain in HIV‐infected individuals, but the mechanisms involved remain unknown. We aimed to assess the effect of these molecules on adipose tissue morphology, function and metabolism.
Method: Morphology and function of subcutaneous (SCAT) and visceral adipose tissue (VAT) were studied in: ‐HIV‐infected patients from the ObeVIH study, at the time of bariatric surgery (BMI 41.8 kg/m2): 14 patients received INSTI (10 dolutegravir, 2 raltegravir, 2 elvitegravir) and 5 an INSTI‐sparing regimen.
‐Uninfected cynomolgus macaques treated or not 15 days with dolutegravir/tenofovir/emtricitabine.
Human Adipose Stem Cells (ASCs) were chronically treated with dolutegravir or raltegravir before or during adipogenesis. Adipogenic capacities, insulin response and extracellular matrix component expression were analyzed.
Results: SCAT from the ObeVIH patients presented peri‐lobular and peri‐adipocyte fibrosis in most samples. Conversely, VAT of INSTI‐treated patient presented a higher level of peri‐adipocyte fibrosis than that of non‐INSTI‐treated patients.
Dolutegravir‐treated macaques presented a higher level of fibrosis and an increased adipocyte size in both SCAT and VAT, when compared to untreated macaques. Adipogenic marker expression was increased in SCAT and VAT, whereas adiponectin expression was decreased in SCAT, suggesting that, despite a pro‐adipogenic effect, dolutegravir may favor insulin resistance.
In ASCs, INSTI‐treatment increased collagen 1 and 6 and a‐smooth‐muscle‐actin expression indicating a pro‐fibrotic effect. In ASC‐differentiated adipocytes, dolutegravir, and to a lesser extent raltegravir, increased lipid accumulation and adipogenic marker expression, decreased adiponectin expression and induced insulin resistance.
Conclusion: We demonstrate here for the first time, by using in vivo and in vitro complementary models, that INSTI exert a direct impact on adipose tissue adipogenesis, fibrosis and insulin resistance. These results, which reveal the adipose tissue toxicity of dolutegravir and raltegravir, are important to explain fat modifications reported in INSTI‐treated HIV‐infected patients.
Вот о чем речь, примерно. А я бы рекомендовал примерно отсюда начинать читать.
