👤 Svetlana Ignjatović

Graves' orbitopathy (GO) is a complex inflammatory disease of the orbit. A potential link between cholesterol metabolism and the occurrence of GO is possible, but still unexplored. This study aims to investigate patients' lipid status, fatty acid content, and cholesterol homeostasis markers, all in relation to the clinical phenotype of GO. This cross-sectional study enrolled 89 consecutive patients with GO of varying degrees of activity and severity. Conventional lipid parameters were measured using routine biochemical methods. Concentrations of cholesterol synthesis and cholesterol absorption markers were analyzed by a GC-FID method. The percentage composition of individual fatty acids was determined by GC-FID. Total concentration of thyrotropin-receptor antibodies was measured by a binding immunoassay (Roche Diagnostics), while their stimulating activity (TSAb) was quantified using a cell-based bioassay (Quidelortho). HDL-C concentration was significantly lower in patients with an active GO compared to an inactive form of GO (p = 0.032). The ApoB/ApoA1 ratio was significantly higher in a more severe GO (p = 0.029). Also, a positive correlation between LDL-C and TSAb levels (ρ = 0.255, p = 0.019) was observed. Lathosterol concentration significantly increased in more severe GO cases (p = 0.045). Moreover, the level of cholesterol synthesis-to-absorption index (CSI/CAI) positively correlated with CAS score (ρ = 0.232, p = 0.048). Palmitic acid was significantly associated with active GO (p = 0.012). The levels of desmosterol, lathosterol, CSI/CAI, and oleic acid were significantly associated with TSAb levels. Alterations in patients' lipid profile and the cholesterol homeostasis were associated with a worse clinical phenotype of GO. Show less

Women with polycystic ovary syndrome (PCOS) has high incidence of metabolic dysfunction-associated steatotic liver disease (MASLD). The development of PCOS-associated MASLD is accelerated by prepubertal obesity, therefore, we analyzed the impact of postnatal overfeeding-induced obesity on the gut microbiota and hepatic lipid metabolism in the PCOS rat model. Wistar rats were divided into 4 groups, where treatment with 5α-dihydrotestosterone (5α-DHT) stimulated hyperandrogenemia (DHT groups), whereas litter size reduction induced early postnatal overfeeding and obesity (SL groups). The fecal microbiota composition and diversity was analyzed by 16S rRNA sequencing. The bacterial metabolites level was measured by mass spectrometry. Hematoxylin-eosin staining, Western blots, and qRT-PCR were used to analyze hepatic lipid metabolism. Our results show that postnatal overfeeding shifted the microbiota composition towards obesity-associated genera, while hyperandrogenemia led to reduced β-diversity and increased abundance of androgen-regulated genera. Interaction of treatments reduced α- and β-diversity and decreased the abundance of beneficial butyrate-producing genera Roseburia, Oscillospira, and Ruminococcus and butyric acid plasma level. Shift in microbiota composition and activity was accompanied by decreased expression of G-protein coupled receptor (GPR) 43, fasting-induced adipocyte factor (FIAF) and increased expression of lipoprotein lipase (LPL). In accordance with altered GPR43 and FIAF/LPL pathway, increased expression of lipogenic transcription factors was observed in SL-DHT animals, but this did not result in hepatic lipid deposition. Our results demonstrated that postnatal overfeeding contributes to decreased richness and changes in gut microbiota composition in the PCOS animal model that is associated with impaired hepatic lipid metabolism, which may accelerate development of MASLD. Show less