REVIEW: Molecular Mechanisms of Latent Inflammation in Metabolic Syndrome. Possible Role of Sirtuins and Peroxisome Proliferator-Activated Receptor Type γ

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I. S. Stafeev^1,2*, M. Y. Menshikov¹, Z. I. Tsokolaeva¹, M. V. Shestakova^3,4, and Ye. V. Parfyonova^1,2

¹Institute of Experimental Cardiology, Russian Cardiological Research and Production Complex, 121552 Moscow, Russia; E-mail: yuristafeev@gmail.com

²Lomonosov Moscow State University, Faculty of Basic Medicine, 119192 Moscow, Russia

³Institute of Diabetes, Endocrinology Research Centre, 117031 Moscow, Russia

⁴Sechenov 1st Moscow State Medical University, 119992 Moscow, Russia

^* To whom correspondence should be addressed.

Received February 12, 2015; Revision received March 23, 2015

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The problem of metabolic syndrome is one of the most important in medicine today. The main hazard of metabolic syndrome is development of latent inflammation in adipose tissue, which promotes atherosclerosis, non-alcoholic fatty liver disease, myocarditis, and a number of other illnesses. Therefore, understanding of molecular mechanisms of latent inflammation in adipose tissue is very important for treatment of metabolic syndrome. Three main components that arise during hypertrophy and hyperplasia of adipocytes underlie such inflammation: endoplasmic reticulum stress, oxidative stress, and hypoxia. Each of these components mediates activation in different ways of the key factor of inflammation – NF-κB. For metabolic syndrome therapy, it is suggested to influence a number of inflammatory signaling components by activating other cell factors to suppress development of inflammation. Such potential factors are peroxisome proliferator-activated receptors type γ that suppress transcription factor NF-κB through direct contact or via kinase of a NF-κB inhibitor (IKK), and also the antiinflammatory transcription factor AP-1. Other possible targets are type 3 NAD⁺-dependent histone deacetylases (sirtuins). There are mutually antagonistic relationships between NF-κB and sirtuin type 1 that prevent development of inflammation in metabolic syndrome. Moreover, sirtuin type 1 inhibits the antiinflammatory transcription factor AP-1. Study of the influence of these factors on the relationship between macrophages and adipocytes, macrophages, and adipose tissue-derived stromal cells can help to understand mechanisms of signaling and development of latent inflammation in metabolic syndrome.

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KEY WORDS: metabolic syndrome, inflammation, NF-κB, peroxisome proliferator-activated receptor type γ, sirtuins

DOI: 10.1134/S0006297915100028

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