Genetic deletion of hormone ‐sensitive lipase in mice reduces cerebral blood flow but does not aggravate the impact of diet‐induced obesity on memory

This study investigated mice with ablated hormone-sensitive lipase (HSL) activity. HSL −/−, HSL+/−, and HSL+/+ mice were exposed to high-fat or control diet for 8 weeks, and tested for behavior and metabolic phenotype. Brain perfusion was measured using MRI, immunofluorescence microscopy in brain slices was used to measure coverage of blood vessels, astrocytes, and microglia, and mass spectrometry was used to measure brain lipid profiles. Altogether, results from these experiments indicate that HSL deletion leads to reduced brain perfusion, without aggravating obesity-induced memory impairment. AbstractHormone-sensitive lipase (HSL) is active throughout the brain and its genetic ablation impacts brain function. Its activity in the brain was proposed to regulate bioactive lipid availability, namely eicosanoids that are inflammatory mediators and regulate cerebral blood flow (CBF). We aimed at testing whether HSL deletion increases susceptibility to neuroinflammation and impaired brain perfusion upon diet-induced obesity. HSL −/−, HSL+/−, and HSL+/+ mice of either sex were fed high-fat diet (HFD) or control diet for 8 weeks, and then assessed in behavior tests (object recognition, open field, and elevated plus maze), metabolic tests (insulin and glucose tolerance tests and indirect calorimetry in metabolic cages) , and CBF determination by arterial spin labeling (ASL) magnetic resonance imaging (MRI). Immunofluorescence microscopy was used to determine coverage ...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research