PURPOSE: Cushing's syndrome is characterized by metabolic disturbances including insulin resistance. Mitochondrial dysfunction is one pathogenic factor in the development of insulin resistance in patients with obesity. We explored whether mitochondrial dysfunction correlates with insulin resistance and other metabolic complications. PATIENTS AND METHODS: We investigated the changes of mRNA expression of genes encoding selected subunits of oxidative phosphorylation system (OXPHOS), pyruvate dehydrogenase (PDH) and citrate synthase (CS) in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM) and mitochondrial enzyme activity in platelets of 24 patients with active Cushing's syndrome and in 9 of them after successful treatment and 22 healthy control subjects. RESULTS: Patients with active Cushing's syndrome had significantly increased body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) and serum lipids relative to the control group. The expression of all investigated genes for selected mitochondrial proteins was decreased in SCAT in patients with active Cushing's syndrome and remained decreased after successful treatment. The expression of most tested genes in SCAT correlated inversely with BMI and HOMA-IR. The expression of genes encoding selected OXPHOS subunits and CS was increased in PM in patients with active Cushing's syndrome with a tendency to decrease toward normal levels after cure. Patients with active Cushing's syndrome showed increased enzyme activity of complex I (NQR) in platelets. CONCLUSION: Mitochondrial function in SCAT in patients with Cushing's syndrome is impaired and only slightly affected by its treatment which may reflect ongoing metabolic disturbances even after successful treatment of Cushing's syndrome.

• Klíčová slova
• Cushing’s syndrome, gene expression, insulin resistance, mitochondrial enzyme activity,
• Publikační typ
• časopisecké články MeSH

Obesity is accompanied by the development of chronic low-grade inflammation in adipose tissue. The presence of chronic inflammatory response along with metabolically harmful factors released by adipose tissue into the circulation is associated with several metabolic complications of obesity such as type 2 diabetes mellitus or accelerated atherosclerosis. The present review is focused on macrophages and lymphocytes and their possible role in low-grade inflammation in fat. Both macrophages and lymphocytes respond to obesity-induced adipocyte hypertrophy by their migration into adipose tissue. After activation and differentiation, they contribute to the development of local inflammatory response and modulation of endocrine function of adipose tissue. Despite intensive research, the exact role of lymphocytes and macrophages within adipose tissue is only partially clarified and various data obtained by different approaches bring ambiguous information with respect to their polarization and cytokine production. Compared to immunocompetent cells, the role of adipocytes in the obesity-related adipose tissue inflammation is often underestimated despite their abundant production of factors with immunomodulatory actions such as cytokines or adipokines such as leptin, adiponektin, and others. In summary, conflicting evidence together with only partial correlation of in vitro findings with true in vivo situation due to great heterogeneity and molecular complexity of tissue environment calls for intensive research in this rapidly evolving and important area.

• Klíčová slova
• Adipocytes, Low-grade inflammation, Lymphocytes, Macrophages, Obesity,
• MeSH
• adipokiny metabolismus   MeSH
• biologické markery metabolismus   MeSH
• cytokiny metabolismus   MeSH
• diabetes mellitus 2. typu etiologie   MeSH
• lidé MeSH
• makrofágy imunologie   MeSH
• myši MeSH
• obezita imunologie   patologie   MeSH
• T-lymfocyty pomocné-indukující imunologie   MeSH
• tuková tkáň cytologie   imunologie   patologie   MeSH
• zánět imunologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• adipokiny MeSH
• biologické markery MeSH
• cytokiny MeSH

BACKGROUND: Monocytes represent a heterogeneous population of cells subdivided according to the expression level of membrane antigens. A pro-inflammatory (intermediate/nonclassical) subpopulation of monocytes is defined by expression of CD16. CD163 seems to be characteristically preferentially expressed by immunosuppressive monocytes. The aim of our study was to evaluate the distribution of monocyte subpopulations in 71 patients with kidney allograft transplantation. RESULTS: The phenotype was evaluated by flow cytometry in defined time points. The proportions of peripheral CD14+CD16+ monocytes were downregulated immediately after the kidney transplantation and basiliximab treatment partially attenuated this trend. The transient downregulation of the CD14+CD16+ subpopulation was adjusted to basal values in two months. The proportions of CD14+CD163+ monocytes were transiently upregulated early after the kidney transplantation and remained higher during the first month in most patients. In ATG treated patients, the expansion of CD14+CD163+ monocytes was delayed but their upregulation lasted longer. In vitro data showed the direct effect of ATG and methylprednisolone on expression of CD16 and CD163 molecules while basiliximab did not affect the phenotype of cultured monocytes. CONCLUSIONS: We assume from our data that kidney allograft transplantation is associated with modulation of monocyte subpopulations (CD14+CD16+ and CD14+CD163+) partially affected by an immunosuppressive regime used.

• MeSH
• antigen CD163 MeSH
• antigeny CD36 metabolismus   MeSH
• antigeny diferenciační B-lymfocytární metabolismus   MeSH
• antigeny diferenciační myelomonocytární metabolismus   MeSH
• CD antigeny metabolismus   MeSH
• dospělí MeSH
• fenotyp MeSH
• homologní transplantace MeSH
• imunofenotypizace MeSH
• imunosupresiva farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipopolysacharidové receptory metabolismus   MeSH
• MHC antigeny II. třídy metabolismus   MeSH
• monocyty účinky léků   imunologie   metabolismus   MeSH
• přežívání štěpu imunologie   MeSH
• průtoková cytometrie MeSH
• receptory buněčného povrchu metabolismus   MeSH
• receptory IgG metabolismus   MeSH
• rejekce štěpu imunologie   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• transplantace ledvin * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigen CD163 MeSH
• antigeny CD36 MeSH
• antigeny diferenciační B-lymfocytární MeSH
• antigeny diferenciační myelomonocytární MeSH
• CD antigeny MeSH
• imunosupresiva MeSH
• invariant chain MeSH Prohlížeč
• lipopolysacharidové receptory MeSH
• MHC antigeny II. třídy MeSH
• receptory buněčného povrchu MeSH
• receptory IgG MeSH