Stroke Induces Prolonged Changes in Lipid Metabolism, the Liver and Body Composition in Mice

Abstract

During recovery, stroke patients are at risk of developing long-term complications that impact quality of life, including changes in body weight and composition, depression and anxiety, as well as an increased risk of subsequent vascular events. The aetiologies and time-course of these post-stroke complications have not been extensively studied and are poorly understood. Therefore, we assessed long-term changes in body composition, metabolic markers and behaviour after middle cerebral artery occlusion in mice. These outcomes were also studied in the context of obesity, a common stroke co-morbidity proposed to protect against post-stroke weight loss in patients. We found that stroke induced long-term changes in body composition, characterised by a sustained loss of fat mass with a recovery of lean weight loss. These global changes in response to stroke were accompanied by an altered lipid profile (increased plasma free fatty acids and triglycerides) and increased adipokine release at 60 days. After stroke, the liver also showed histological changes indicative of liver damage and a decrease in plasma alanine aminotransferase (ALT) was observed. Stroke induced depression and anxiety-like behaviours in mice, illustrated by deficits in exploration, nest building and burrowing behaviours. When initial infarct volumes were matched between mice with and without comorbid obesity, these outcomes were not drastically altered. Overall, we found that stroke induced long-term changes in depressive/anxiety-like behaviours, and changes in plasma lipids, adipokines and the liver that may impact negatively on future vascular health.

A metabolic handbook for the COVID-19 pandemic

“…24 ). During recovery, patients with stroke are at risk of future vascular events 43 . Long-lasting changes in metabolism and energy balance appear to be important drivers of these future events.…”

“…Long-lasting changes in metabolism and energy balance appear to be important drivers of these future events. Weight loss and malnutrition are frequently observed in patients recovering from stroke 43 . This weight loss has traditionally been assumed to be due to cachexia; however, recent data suggest that sustained loss of adipose tissue may also contribute.…”

“…This weight loss has traditionally been assumed to be due to cachexia; however, recent data suggest that sustained loss of adipose tissue may also contribute. In a stroke model, mice have been found to exhibit prolonged changes in body composition characterized by an initial loss of adipose tissue mass, which is subsequently sustained at lower levels 43 . This effect is associated with prolonged changes in the levels of plasma lipids including free fatty acids and triglycerides 43 .…”

“…In a stroke model, mice have been found to exhibit prolonged changes in body composition characterized by an initial loss of adipose tissue mass, which is subsequently sustained at lower levels 43 . This effect is associated with prolonged changes in the levels of plasma lipids including free fatty acids and triglycerides 43 . Sustained elevated levels of free fatty acids and triglycerides can lead to cardiovascular abnormalities in people who have recovered from SARS and potentially COVID-19 ( Fig.…”

Traumatic Brain Injury Impairs Systemic Vascular Function Through Altered Lipid Metabolism and Disruption of Inward-Rectifier Potassium (Kir2.1) Channels

“…30 Disturbed lipid metabolism in severely injured trauma patients is a strong predictor of clinical outcome. 31 Altered fatty acid metabolism has been demonstrated in controlled animal models of stroke 32 and tissue injury with hemorrhagic shock, including derangements in mono- and poly-unsaturated fatty acid mobilization and oxidation products. 17 We hypothesized that severe TBI, even without concomitant shock or hypoxia, would cause significant metabolic responses.…”