Blood-brain barrier integrity and transport of major hormones are unchanged in mice with euglycemic hyperinsulinemia.

Abstract

High fat diet (HFD) consumption increases the risk of metabolic syndrome as manifested by insulin resistance, fatty liver, hypertriglyceridemia, and diabetes mellitus type II (DM). Blood-brain barrier (BBB) disruptions and impaired BBB transport of metabolic hormones, including leptin, insulin, and ghrelin, occur in DM and contribute to metabolic dysregulation and cognitive impairment. However, it is unclear whether the BBB changes are caused by the HFD, obesity, insulin resistance, elevated glucose or triglyerceride levels, or other aspects of the metabolic syndrome. This study examined the effects of chronic HFD and an early stage of metabolic syndrome on BBB disruption and transport of insulin, leptin, and ghrelin. Mice on the HFD demonstrated obesity, increase in insulin, leptin, plasminogen activator inhibitor-1 (PA-1), and resistin, fatty liver and hyperglycerolemia, without elevations in glucose, triglycerides, ghrelin, glucagon, GIP, or GLP-1. The vascular markers of sucrose and albumin did not show BBB disruption. HFD did not alter the rate of insulin, leptin, or ghrelin transport across the BBB. However, leptin binding to the luminal surface of the BBB was greater in the hypothalamus and reduced for the rest of the brain with HFD treatment. The liver uptake of insulin, leptin, and ghrelin was reduced in the HFD group. Overall, our findings indicate that chronic HFD consumption with concomitant obesity and insulin resistance in the absence of hyperglycemia does not result in BBB disruption or altered BBB permeability to key metabolic hormones, but may selectively affect vascular binding of important metabolic hormones in the brain and liver.