Prolonged intake of desloratadine: mesenteric lymphatic vessel dysfunction and development of obesity/metabolic syndrome.

This study aimed to establish mechanistic links between the prolonged intake of desloratadine, a common H1 receptor blocker (i.e. antihistamine), and development of obesity and metabolic syndrome. Male Sprague-Dawley rats were treated orally for 16 weeks with desloratadine. We analyzed the dynamics of body weight gain; tissue fat accumulation/density; contractility of isolated mesenteric lymphatic vessels; levels of blood lipids, glucose and insulin; together with parameters of liver function. Prolonged intake of desloratadine induced development of an obesity-like phenotype and signs of metabolic syndrome. These alterations in the body included excessive weight gain, increased density of abdominal subcutaneous fat and intracapsular brown fat, high blood triglycerides with an indication of their re-routing towards portal blood, high HDL, high fasting blood glucose with normal fasting and non-fasting insulin levels (insulin resistance), high liver/body weight ratio, and liver steatosis (fatty liver). These changes were associated with dysfunction of mesenteric lymphatic vessels, specifically high lymphatic tone and resistance to flow together with diminished tonic and abolished phasic responses to increases in flow, (i.e. greatly diminished adaptive reserves to respond to postprandial increases in lymph flow). The role of nitric oxide in this flow-dependent adaptation was abolished, with remnants of these responses controlled by lymphatic vessel-derived histamine. Our current data, considered together with reports in the literature, support the notion that millions of the United States population are highly likely affected by under-evaluated, lymphatic-related side effects of antihistamines, and may develop obesity and metabolic syndrome due to the prolonged intake of this medication.