Endocrine Abstracts

Introduction: Obesity is associated with a plethora of metabolic and physiological side effects. Excess adiposity is associated with raised intracranial pressure (ICP) in obesity, where raised ICP sequalae include headache and visual decline in humans. We aimed to assess the effects of diet induced obesity (DIO) on ICP and related neuroophthalmological outcomes of headache behavior and retinal anatomy in rats.

Methods: Female Sprague-Dawley rats received high fat diet (60% fat) or matched control diet (10% fat) for 15-17 weeks. Following the diet, rats were implanted with telemetric ICP probes. Cutaneous allodynia was assessed via electric von frey and retinal anatomy was assessed by optical coherence tomography. Body composition was determined by dual x-ray absorptiometry.

Results: On the day of ICP surgery (baseline), DIO rats were 15% heavier than controls (365.9± 37.8 vs 316± 17.3 g, P = 0 .002) with a greater abdominal fat percentage (43.2± 7.2 vs 28.9± 3.2 %, P < 0.0001). All rats had similar fasting glucose at baseline (6.3± 0.5 vs 5.8± 0.7 mmol/l, P = 0 .43). DIO rats had raised ICP at baseline (2.77± 0.6 mmHg vs -0.17± 0.7, P = 0 .0052) and the following 10 days (P = 0.0075) which correlates with abdominal adiposity (r = 0.54, P = 0 .016). DIO rats demonstrate cephalic cutaneous allodynia (163.1± 8.0 vs 213.8± 5.1 g, P < 0.0001) at baseline, accordingly Calca and Trpv1 expression was raised in the trigeminal ganglia. The cephalic threshold negatively correlates with abdominal fat percentage (r=-0.65, P = 0 .0005). At baseline, DIO rats had swollen retinal nerve fibre layers (RNFL) (28.8± 0.6 vs 24.8± 1.1 μm, P = 0 .0026), and RNFL thickness positively correlates with ICP (r = 0.639, P = 0 .0058).

Discussion: Our data highlight that obesity increases ICP, accompanied by increased headache behavior and altered retinal anatomy, mimicking clinical findings. Our unique model will facilitate deeper understanding of the molecular underpinnings of raised ICP and the development of novel therapeutics to treat raised ICP.