Drugs Involved in Dyslipidemia and Obesity Treatment: Focus on Adipose Tissue

Abstract

Metabolic syndrome can be defined as a state of disturbed metabolic homeostasis characterized by visceral obesity, atherogenic dyslipidemia, arterial hypertension, and insulin resistance. The growing prevalence of metabolic syndrome will certainly contribute to the burden of cardiovascular disease. Obesity and dyslipidemia are main features of metabolic syndrome, and both can present with adipose tissue dysfunction, involved in the pathogenic mechanisms underlying this syndrome. We revised the effects, and underlying mechanisms, of the current approved drugs for dyslipidemia and obesity (fibrates, statins, niacin, resins, ezetimibe, and orlistat; sibutramine; and diethylpropion, phentermine/topiramate, bupropion and naltrexone, and liraglutide) on adipose tissue. Specifically, we explored how these drugs can modulate the complex pathways involved in metabolism, inflammation, atherogenesis, insulin sensitivity, and adipogenesis. The clinical outcomes of adipose tissue modulation by these drugs, as well as differences of major importance for clinical practice between drugs of the same class, were identified. Whether solutions to these issues will be found in further adjustments and combinations between drugs already in use or necessarily in new advances in pharmacology is not known. To better understand the effect of drugs used in dyslipidemia and obesity on adipose tissue not only is challenging for physicians but could also be the next step to tackle cardiovascular disease.

Sex and gender differences in axial spondyloarthritis: myths and truths

“…Women have greater deposits of subcutaneous fat (SAT), whereas men have more visceral fat (VAT), which is located intra-abdominally [ 30 ]. Interestingly, adipose tissue acts as an endocrine organ, secreting not only adipokines, which can act as pro-(leptin) or anti-(adiponectin) inflammatory, but also cytokines, such as the pro-inflammatory cytokine TNF-α [ 31 ]. One study reported that female patients with higher disease activity scores [Ankylosing Spondylitis Disease Activity Score (ASDAS) and BASDAI] had a significantly higher percentage of body fat (BF) or fat mass index (FMI) [ 32 ].…”

Strategies and methods for the correction of obesity and associated cardiovascular risk

“…Наконец, наиболее глобальная стратегия коррекции ССР при ожирении должна быть направлена на обратное развитие процессов ремоделирования и дисфункции жировой ткани, восстановление физиологического характера протеомного и секретомного профилей адипоцитов и типа экспансии жировой ткани, редукцию эндогенного иммунного ответа жировой ткани, местных паракринных взаимодей ствий и системного воспалительного статуса [19][20][21][22].…”

“…Фибраты также ускоряют процессы липолиза, способствуют редукции ВЖТ, увеличению термогенеза посредством регуляции экспрессии генов "разобщающих" факторов и процессов "коричневения" белых адипоцитов, экспрессии адипонектина, сиртуина-1 и васпина, снижению уровней провоспалительных адипокинов, улучшению чувствительности адипоцитов к инсулину [22,50].…”

“…Перспективные методы коррекции риска. В качестве возможных направлений коррекции ожирения и ассоциированного ССР изучаются методы, направленные на модификацию транскриптома эктопической (эпикардиальной) ВЖТ, применение различных микро-РНК, иризина (миокина, высвобождаемого при физических нагрузках), агонистов рецепторов к адипонектину, адипокинов бурой жировой ткани, аналогов фактора роста фибробластов 21-го типа, костного морфогенного протеина 7-го типа [20][21][22]53].…”

Application of ELISA Technique and Human Microsomes in the Search for 11β-Hydroxysteroid Dehydrogenase Inhibitors

“…11 β -HSD1 dehydrogenase is found mainly in adipose tissue, liver, and lungs, whereas 11 β -HSD2 is expressed in tissues associated with mineralocorticoid activity, namely, kidney, placenta, large intestine, and salivary glands. It converts cortisol into metabolically weak cortisone [26, 27], while the role of 11 β -HSD1 is to convert cortisone to the active form of cortisol (Figure 1).…”