BACKGROUND: FTO, a gene recently discovered in genomewide associated studies for type 2 diabetes mellitus (T2D), play an important role in the management of energy homeostasis, nucleic acid demethylation and regulation of body fat mass by lipolysis. The aim of this study was to analyze the association of FTO rs8050136 A>C genetic variant with clinical and biochemical parameters of T2D in the population of West Balkan region (Bosnians and Herzegovinians and Kosovars). METHODS: The study included 638 patients with T2D and prediabetes and 360 healthy controls of both genders, aged from 40 to 65 years. Patients were recruited at the Clinical Centre University of Sarajevo, University Hospital of Clinical Centre in Banja Luka, General Hospital in Tešanj and Health Centre in Prizren. Genotyping of analyzed FTO polymorphism rs8050136 A>C was performed by qPCR allelic discrimination. RESULTS: Genotype frequencies of the analyzed polymorphism were comparable between patients with T2D, prediabetic patients, and healthy population. Logistic regression analyses didn't show significant association of FTO rs8050136 A allele with increased risk of T2D. However, risk A allele was significantly associated with higher levels of HbA1c, insulin, HOMA-IR index, diastolic blood pressure, and inflammatory markers (fibrinogen and leukocytes) as well as showed tendency of association with increased values of obesity markers (BMI, waist and hip circumference). CONCLUSIONS: Results of our study showed a significant association of FTO genetic variant rs8050136 A>C with the major markers of insulin resistance, obesity and inflammation, opening new avenues for solving many unclear questions in the pathogenesis of T2D.

UVOD: FTO, gen koji je u cjelogenomskim studijama povezanosti, nedavno otkriven kao kandidatni gen za tip 2 dijabetes (T2D), ima značajnu ulogu u upravljanju energetske homeostaze, demetilaciji nukleinskih kiselina i regulaciji indeksa tjelesne mase (ITM) tako što reguliše proces lipolize. Cilj studije je bio da analiziramo povezanost FTO rs8050136 A>C genetske varijante sa kliničkim i biohemijskim parametrima T2D u populacijama regiona Zapadnog Balkana (Bosancima i Hercegovcima i Kosovarima). METODE: U studiju je uključeno 638 pacijenata oboljelih od T2D, predijabetesa, i 360 zdravih kontrola, oba spola, starosti od 40 do 65 godina. Pacijenti se regrutovani u Kliničkom centru Univerziteta u Sarajevu, Univerzitetskoj bolnici Kliničkog centra u Banja Luci, Opštoj bolnici u Tešnju i Domu zdravlja u Prizrenu. Genotipizacija FTO genetskog polimorfizma rs8050136 A>C je analizirana korištenjem metode qPCR alelne diskriminacije. REZULTATI: Frekvencije genotipova analiziranog polimorfizma uspoređivane su između pacijenata sa T2D, predijabetesom i zdravih ispitanika. Također, rezultati logistike analize nisu pokazali značajnu povezanost A alela FTO rs8050136 polimorfizma sa povećanim rizikom razvoja T2D. Međutim, rizični A alel je pokazao značajnu asociranost sa višim vrijednostima HbA1c, inzulina, HOMA IR indeksa, diastolnog krvnog pritiska, i inflamatornih markera (fibrinogena i leukocita), kao i tendenciju povezanosti sa povišenim vrijednostima parametara gojaznosti (ITM, opseg struka i opseg kukova). ZAKLJUČAK: Rezultati naše studije pokazali su značajnu povezanost FTO genetske varijante rs8050136 A>C sa najbitnijim markerima inzulinske rezistencije, gojaznosti i inflamacije, otvarajući na taj način nove puteve i mogućnosti riješavanja mnogih nejasnih pitanja vezanih za patogenezu T2D.

• Klíčová slova
• FTO gene, Type 2 diabetes, gene variant, inflammation, obesity,
• Publikační typ
• časopisecké články MeSH

Maternal obesity predisposes offspring to metabolic dysfunction and Non-Alcoholic Fatty Liver Disease (NAFLD). Melanocortin-4 receptor (Mc4r)-deficient mouse models exhibit obesity during adulthood. Here, we aim to determine the influence of the Mc4r gene on the liver of mice subjected to perinatal diet-induced obesity. Female mice heterozygous for Mc4r fed an obesogenic or a control diet for 5 weeks were mated with heterozygous males, with the same diet continued throughout pregnancy and lactation, generating four offspring groups: control wild type (C_wt), control knockout (C_KO), obese wild type (Ob_wt), and obese knockout (Ob_KO). At 21 days, offspring were genotyped, weaned onto a control diet, and sacrificed at 6 months old. Offspring phenotypic characteristics, plasma biochemical profile, liver histology, and hepatic gene expression were analyzed. Mc4r_ko offspring showed higher body, liver and adipose tissue weights respect to the wild type animals. Histological examination showed mild hepatic steatosis in offspring group C_KO. The expression of hepatic genes involved in regulating inflammation, fibrosis, and immune cell infiltration were upregulated by the absence of the Mc4r gene. These results demonstrate that maternal obesogenic feeding during the perinatal period programs offspring obesity development with involvement of the Mc4r system.

• Klíčová slova
• Non-Alcoholic Fatty Liver Disease, developmental programming, intra-abdominal fat, maternal nutrition, obesity,
• MeSH
• alanintransaminasa krev   MeSH
• aspartátaminotransferasy krev   MeSH
• fyziologie výživy v mateřství * MeSH
• játra metabolismus   MeSH
• krevní glukóza metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši knockoutované MeSH
• myši obézní MeSH
• myši MeSH
• obezita genetika   MeSH
• perinatální péče MeSH
• receptor melanokortinový typ 4 nedostatek   genetika   MeSH
• regulace genové exprese MeSH
• těhotenství MeSH
• triglyceridy krev   MeSH
• zpožděný efekt prenatální expozice genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alanintransaminasa MeSH
• aspartátaminotransferasy MeSH
• krevní glukóza MeSH
• MC4R protein, mouse MeSH Prohlížeč
• receptor melanokortinový typ 4 MeSH
• triglyceridy MeSH