Pancreatic inflammation induced by hypothyroidism in female rabbits is associated with cholesterol accumulation and a reduced expression of CYP51A1, FXRβ, and PPARβ/δ

• Published in: Anatomical record (Hoboken, N.J. : 2007) N.J. : 2007), 2024-10
• Main Authors: Rojas-Juárez, Rubicela, Rodríguez-Castelán, Julia, Cuatecontzi-Fuentes, Ismael, Mendez-Tepepa, Maribel, Cruz-Lumbreras, Rosalía, Rodríguez-Antolín, Jorge, Arroyo-Helguera, Omar Elind, Cuevas-Romero, Estela
• Format: Article
• Language: English
• ISSN: 1932-8486; 1932-8494; 1932-8494
• DOI: 10.1002/ar.25590

In women and animal models, hypothyroidism induces hypercholesterolemia, pancreatitis, and insulitis. We investigated whether lipids are involved in the effects of hypothyroidism in the pancreas. Control (n = 6) and hypothyroid (n = 6) adult female rabbits were used. We quantified serum and pancreatic triacylglycerol and total cholesterol levels, the oxidative and antioxidant status, and the expression of low-density lipoprotein cholesterol receptor (LDLR) in the pancreas. Inflammation of the pancreas was evaluated by infiltration of immune cells positive to CD163 and α-farnesoid receptor (FXRα). Other lipid players involved in both inflammation and insulin secretion of the pancreas, such as lanosterol 14-α-demethylase (CYP51A1), β-farnesoid receptor (FXRβ), 3β-hydroxysteroid dehydrogenase (3β-HSD), and peroxisome proliferator-activated receptor β (PPARβ/δ), were quantified. Groups were compared by t-Student or U-Mann-Whitney tests (p ≤ 0.05). Hypothyroidism induced hypercholesterolemia and a high cholesterol accumulation in the pancreas of female rabbits, without affecting oxidative or antioxidative status nor the expression of LDLR. The pancreas of hypothyroid females showed inflammation identified by a great infiltration of immune cells, macrophages CD163+, and loss of expression of FXRα+ in immune cells. Moreover, a reduced expression of CYP51A1, FXRβ, and PPARβ/δ, but not 3β-HSD, in the hypothyroid pancreas was found. Pancreatitis and insulitis promoted by hypothyroidism may be related to the accumulation of cholesterol, lanosterol actions, and the activation of PPARβ/δ. All inflammatory markers evaluated in this study are related to glucose regulation, suggesting the link between hypothyroidism and diabetes.