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

Abstract

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 for 16 wk with desloratadine. We analyzed the dynamics of body weight gain, tissue fat accumulation/density, contractility of isolated mesenteric lymphatic vessels, and 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 rerouting toward portal blood, high HDL, high fasting blood glucose with normal fasting and nonfasting 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 underevaluated, lymphatic-related side effects of antihistamines and may develop obesity and metabolic syndrome due to the prolonged intake of this medication. NEW & NOTEWORTHY Prolonged intake of desloratadine induced development of obesity and metabolic syndrome associated with dysfunction of mesenteric lymphatic vessels, high lymphatic tone, and resistance to flow together with greatly diminished adaptive reserves to respond to postprandial increases in lymph flow. Data support the notion that millions of the USA population are highly likely affected by underevaluated, lymphatic-related side effects of antihistamines and may develop obesity and metabolic syndrome due to the prolonged intake of this medication.

Emerging Role of Lymphatics in the Regulation of Intestinal Lipid Mobilization

“…Defects in the lymphatic system have been associated with metabolic disorders, including metabolic syndrome, obesity, diabetes, and atherosclerosis in animal models. Lymphatic function was impaired in rats with metabolic syndrome (Zawieja et al, 2012;Gasheva et al, 2019) and in obese mice (Weitman et al, 2013;Blum et al, 2014;García Nores et al, 2016), and defective lymphatics contributed to obesity and metabolism syndrome (Escobedo and Oliver, 2017;Gasheva et al, 2019). Diabetes in mice was associated with impaired lymphangiogenesis and disrupted lymphatic integrity (Scallan et al, 2015;Wu et al, 2018).…”

Assessing the effect of prolonged use of desloratadine on adipose Brillouin shift and composition in rats

“…These studies shine light on a potential impact on the health of millions of people who routinely take second‐generation antihistamines to alleviate their allergy symptoms. Our recent comprehensive study indicated a link between a prolonged intake of desloratadine, a common second‐generation antihistamine, and development of obesity‐like phenotype and metabolic syndrome in rats [13]. That study included brief results on the desloratadine‐induced changes in the elasticity of AT as measured by Brillouin elastography.…”

Antihistamines Increase Body Mass Index Percentiles and Z-Scores in Hispanic Children

“…Despite those previous findings in the literature, the link between allergies, intake of antihistamines, and obesity has not been studied clearly and is still a potentially under-recognized pathology. An animal study was recently designed and carried by Gasheva et al [ 9 ] that implemented daily desloratadine treatment in rats for 16 weeks, an equivalent of 8 years in human life [ 12 ]. The study results indicate that prolonged intake of desloratadine induced the development of an obesity-like phenotype and signs of metabolic syndrome.…”

“…Moreover, the authors found that animals had high serum triglycerides with signs of deflection towards portal blood, high fasting glucose with signs of insulin resistance, elevated liver to body weight ratio, and liver steatosis suggestive of fatty liver. A dysfunction of mesenteric lymphatic vessels was associated with those findings, precisely high MLV tone, and resistance to flow with lack of proper adaptive reserves to increased lymphatic flow in the post-prandial state [ 9 ].…”

“…The blockade of histamine’s intrinsic action modifies the flow-dependent post-prandial adaptation of mesenteric lymphatic contractility and tone. Long-term use of antihistamines leads to increased resistance to lymph flow, accumulation of lipids in the mesentery, and malabsorption [ 7 , 8 , 9 ]. Moreover, a recent study by Gasheva et al performed on rats treated with the H1 receptor blocker desloratadine for 16 weeks found an association between H1 blockade and weight gain, increased density of subcutaneous fat, hepatic steatosis, fat malabsorption, and abnormal lipid profiles [ 9 ].…”