Comparative Analysis of Selected UGT and SULT mRNA Expression in Non-Obese Rat Models of Metabolic Syndrome

Background: Metabolic syndrome (MetS) is a cluster of risk factors increasing the likelihood of cardiovascular and metabolic diseases. Objectives: This study investigated the relative mRNA expression of key hepatic and intestinal phase II drug-metabolising enzymes, specifically UDP-glycosyltransferases (UGTs) and sulfotransferases (SULTs), in four non-obese rat models of MetS characterised by different dominant traits: the hereditary hypertriglyceridaemic (HHTg) rat, spontaneously hypertensive rat (SHR), SHR-expressing transgenic human C-reactive protein (SHR-CRP) rat, and bilaterally ovariectomised female Wistar (W-OVX) rat, compared to Wistar controls. Methods: Gene expression was quantified by RT-PCR with data normalised using the ΔΔCt method. Results: Measurements showed significant model-specific differences, especially in the liver. HHTg rats exhibited significant hepatic suppression of Ugt1a9 (-90%) and undetectable Ugt2b transcripts, alongside compensatory upregulation of Sult1a1 (196%) and Sult1b1 (277%). The SHR model showed significant hepatic upregulation of Ugt1a1 (330%), Sult1a1 (266%), and Sult1b1 (328%). Chronic inflammation in SHR-CRP rats caused a significant decrease in hepatic Ugt1a1, whereas a significant induction occurred in the intestine. Oestrogen deprivation (W-OVX) led to significant downregulation of hepatic Ugt1a6 and Ugt1a9. Conclusions: These findings highlight that the alterations in phase II metabolism strongly depend on the pathophysiological context, potentially affecting drug disposition in preclinical models.