AIM: Development of type 2 diabetes (T2DM) is associated with disturbances in immune and metabolic status that may be reflected by an altered gene expression profile of peripheral blood mononuclear cells (PBMC). To reveal a potential family predisposition to these alterations, we investigated the regulation of gene expression profiles in circulating CD14+ and CD14- PBMC in fasting conditions and in response to oral glucose tolerance test (OGTT) in glucose tolerant first-degree relatives (FDR) of T2DM patients and in control subjects. MATERIALS AND METHODS: This work is based on the clinical study LIMEX (NCT03155412). Non-obese 12 non-diabetic (FDR), and 12 control men without family history of diabetes matched for age and BMI underwent OGTT. Blood samples taken before and at the end of OGTT were used for isolation of circulating CD14+ and CD14- PBMC. In these cells, mRNA levels of 94 genes related to lipid and carbohydrate metabolism, immunity, and inflammation were assessed by qPCR. RESULTS: Irrespectively of the group, the majority of analyzed genes had different mRNA expression in CD14+ PBMC compared to CD14- PBMC in the basal (fasting) condition. Seven genes (IRS1, TLR2, TNFα in CD14+ PBMC; ABCA1, ACOX1, ATGL, IL6 in CD14- PBMC) had different expression in control vs. FDR groups. OGTT regulated mRNA levels of nine genes selectively in CD14+ PBMC and of two genes (ABCA1, PFKL) selectively in CD14-PBMC. Differences in OGTT-induced response between FDR and controls were observed for EGR2, CCL2 in CD14+ PBMC and for ABCA1, ACOX1, DGAT2, MLCYD, and PTGS2 in CD14- PBMC. CONCLUSION: This study revealed a different impact of glucose challenge on gene expression in CD14+ when compared with CD14- PBMC fractions and suggested possible impact of family predisposition to T2DM on basal and OGTT-induced gene expression in these PBMC fractions. Future studies on these putative alterations of inflammation and lipid metabolism in fractionated PBMC in larger groups of subjects are warranted.

• Keywords
• CD14+ cells, CD14− cells, first-degree relatives, gene expression, oral glucose tolerance test, peripheral blood mononuclear cells, type 2 diabetes mellitus,
• MeSH
• Biomarkers metabolism   MeSH
• Diabetes Mellitus, Type 2 genetics   metabolism   pathology   MeSH
• Adult MeSH
• Genetic Predisposition to Disease * MeSH
• Glucose Tolerance Test MeSH
• Blood Glucose analysis   MeSH
• Leukocytes, Mononuclear metabolism   pathology   MeSH
• Humans MeSH
• Lipopolysaccharide Receptors metabolism   MeSH
• Gene Expression Regulation * MeSH
• Case-Control Studies MeSH
• Transcriptome * MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers MeSH
• CD14 protein, human MeSH Browser
• Blood Glucose MeSH
• Lipopolysaccharide Receptors 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.

• Keywords
• Adipocytes, Low-grade inflammation, Lymphocytes, Macrophages, Obesity,
• MeSH
• Adipokines metabolism   MeSH
• Biomarkers metabolism   MeSH
• Cytokines metabolism   MeSH
• Diabetes Mellitus, Type 2 etiology   MeSH
• Humans MeSH
• Macrophages immunology   MeSH
• Mice MeSH
• Obesity immunology   pathology   MeSH
• T-Lymphocytes, Helper-Inducer immunology   MeSH
• Adipose Tissue cytology   immunology   pathology   MeSH
• Inflammation immunology   pathology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Adipokines MeSH
• Biomarkers MeSH
• Cytokines MeSH