OR21-04 Developmental Programming: Origin of MASLD in a Sheep Model of Polycystic Ovary Syndrome and Impact of Postnatal Obesity on its Severity
Abstract
Abstract Disclosure: K.M. Halloran: None. J. Sustaita: None. R. Cardoso: None. V. Padmanabhan: None. Metabolic dysfunction is associated with insulin resistance and a hyper-inflammatory/oxidative state which is worsened by obesity. This can lead to metabolic dysfunction-associated steatotic liver disease (MASLD). The trajectory of MASLD may be established early in life, and animal models provide a means to study the developmental origins of this disease. Prenatal testosterone (T) treated sheep from gestational days (GD) 30-90 manifest insulin resistance, a hyper-inflammatory/oxidative state, and hepatic lipid and collagen accumulation, like MASLD, in normal weight adults. While postnatal obesity could further exacerbate this phenotype, the severity of the phenotype in the GD 30-90 model will likely mask effects of postnatal obesity. Prenatal T from GD 60-90 results in a mild metabolic phenotype, allowing assessment of amplifying effects of postnatal obesity on the prenatally programmed phenotype. We hypothesized that prenatal T treatment from GD 60-90 causes liver disease that is worsened by obesity in adults. Pregnant sheep received twice weekly im injections of either T propionate (100 mg) in corn oil or vehicle control (C) from GD 60-90 (term ∼147 days). At 5 months of age, female offspring from C and T groups were fed a maintenance (M) diet, while another T offspring group were overfed (O). Ewes (n=6/group) were euthanized and liver collected at ∼3 years of age. Frozen…
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