(761.6) Metabolic effect of orchidectomy on C57BL6/J mice exposed to intermittent hypoxia

Poster Board Number: E509

Gauthier Ganouna-Cohen (Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ)), Britanny Blachot Minassian (Université de Grenoble), François Marcouiller (Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ)), Vincent Joseph (Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ))

Introduction: Sleep apnea (SA) is characterized by obstructions of the airways or cessation of breathing during sleep leading to intermittent hypoxia (IH). IH is a source of oxidative stress and inflammation altering the functions of pancreas, liver, muscles and adipose tissue. As a consequence, sleep apnea patients have a high prevalence of insulin resistance and glucose intolerance which can lead to type 2 diabetes. In mice, exposures to IH induce adipose tissue inflammation, liver injury and worsen the pancreatic β-cell injury in a model of diabetes. While these effects are associated with insulin resistance, glucose tolerance is improved, notably via an enhanced glucose uptake by skeletal muscles. In men, sleep apnea and diabetes are also characterized by low testosterone levels. Interestingly, testosterone levels are positively corelated with insulin sensitivity in human, and low testosterone levels can be associated with inflammation, oxidative stress and insulin resistance. Therefore, we tested the hypothesis that testosterone modulates the metabolic alterations induced by IH in male mice.

Method: We used intact (Sham) or orchidectomized (ORX) C57BL/6J male mice exposed for 14 days to IH (12h / day, 10 cycles / h, 6% nadir oxygen) or normoxia (Nx). The animals were weighed, and we assessed body composition in terms of lean and fat mass, as well as fluid content by using a small animal MRI scanner before the surgery, before IH or Nx exposures and at the end of the protocol. The day after the last IH session, mice were fasted for 6h, we measured fasting glycaemia and insulinemia then we performed a glucose tolerance test.

Results: In Sham mice, IH decreased bodyweight and fat mass. This was associated with a decrease of fasting glycaemia, insulinemia and HOMA-IR (index of insulin resistance), and improved glucose sensitivity. ORX decreased bodyweight and lean tissue mass, associated with lower fasting glycemia, insulinemia, HOMA-IR and improved whole body glucose sensitivity. ORX mice exposed to IH had a decrease of both fat and lean tissue mass leading to further reduction of body weight. However, there was no additive effects of ORX and ORX IH for fasting glycaemia, insulinemia, HOMA-IR and glucose sensitivity.

Conclusion: IH and ORX respectively reduce fat and lean tissue mass, and these effects are additive when both stimuli are applied simultaneously. Contrastingly, there are no additive effects of IH and ORX on the metabolic parameters reported here.

IRSC and Ramp;eacute;seau en Santamp;eacute; Respiratoire du Quamp;eacute;bec





metabolic test; Body composition