H1-antihistamines exacerbate high fat diet-induced fatty liver disease in wild type but not in apolipoprotein E-knockout mice (1116.10)

Activation of histamine receptor 1 (H1R) reduces adiposity in mice, and chronic use of H1-antihistamines (H1-AH) increase weight gain in obese patients. Apolipoprotein E (ApoE) plays a major role in lipid transport. We examined the effects of chronic blockade of H1R by cetirizine or fexofenadine, two therapeutic H1-AH, on fatty liver disease, adiposity and weight gain in wild-type (WT) and ApoE-knockout (ApoE-/-) mice. Eight week old male WT or ApoE-/- mice were fed a high fat diet, and concurrently treated with equivalent therapeutic doses of either cetirizine or fexofenadine via drinking water for 3 months. H1-HA treatments increased weight gain, visceral adiposity, liver weight and macrovesicular hepatosteatosis in WT mice, but not in ApoE-/- mice. These changes were independent of food intake. Serum markers of liver injury tended to increase in H1-HA-treated WT mice in association with increased macrovesicular hepatosteatosis. Microvesicular hepatosteatosis and lobular inflammation were not affected b...