Increased sleep time and reduced energy expenditure contribute to obesity after ovariectomy and a high fat diet.

In this study we examined if sleep time, caloric intake and energy expenditure are important contributors to development of ovariectomy-induced obesity in mice fed control or high fat diet (HFD). Twelve female mice at 6 weeks of age were divided into 2 groups: Sham (n = 5) and ovariectomized (OVX, n = 7). Mice were fed control diet for 9 weeks and shifted to HFD for additional 9 weeks. Food intake and body weight were measured daily and body composition was measured weekly by EchoMRI. Energy expenditure (EE), oxygen consumption (VO2), motor activity (MA) and sleep time were monitored at week 9 during control diet and HFD. OVX did not alter caloric intake, body weight or body composition, MA, sleep time or fasting blood glucose, but slightly reduced EE compared to Sham mice on control diet. After HFD feeding, OXV mice had similar caloric intake, lean mass, MA, and blood glucose levels but had significantly greater weight gain (8.2 ±â€¯1.0 vs. 4.8 ±â€¯1.2 g, p < 0.05), increased fat mass and sleep time, and reduced EE (3.3 ±â€¯0.4 vs. 5.5 ±â€¯0.2 kcal/h) and VO2 (1.12 ±â€¯0.01 vs. 1.83 ±â€¯0.05 ml/min) compared to Sham group. Daytime blood pressure was higher while nighttime heart rate was lower in OVX group. These results suggest that OVX may not substantially alter body weight or body composition in mice fed a normal diet, but when combined with HFD it increases sleep time and reduces EE, leading to greater weight gain and adiposity without altering food intake.

Role of autonomic nervous system in chronic CNS-mediated antidiabetic action of leptin.

This study tested whether ganglionic blockade or hepatic vagotomy attenuates the chronic central nervous system (CNS)-mediated antidiabetic and cardiovascular effects of leptin. Male Sprague-Dawley rats were instrumented with telemetry probes and arterial and venous catheters for determination of blood pressure (BP), heart rate (HR), blood sampling, and intravenous (iv) infusions. An intracerebroventricular (ICV) cannula was placed into the brain lateral ventricle for infusion of leptin or vehicle. After control measurements, streptozotocin (STZ) was injected iv (50 mg/kg) to induce diabetes, and 5 days later leptin (n = 6) or saline vehicle (n = 5) was infused ICV for 12 days via osmotic pumps. Beginning on day 6 of leptin treatment, the ganglionic blocker hexamethonium (15 mg·kg-1·day-1 iv) was infused, while leptin infusion was continued, to assess the role of the autonomic nervous system. Induction of diabetes was associated with increases in blood glucose (98 ± 7 to 350 ± 19 mg/dl), food intake (23 ± 3 to 43 ± 3 g/day), decreases in HR (-70 ± 11 beats/min), polyuria, and increased water consumption, which were all completely normalized by ICV leptin infusion. Although hexamethonium attenuated leptin's effect on HR, it failed to impair leptin's ability to restore euglycemia or to prevent the polyuria or increased water intake in STZ-diabetic rats. We also found that after pretreatment with hexamethonium (n = 8), ICV leptin infusion, during continued ganglionic blockade, completely normalized blood glucose in diabetic rats. In addition, selective hepatic vagotomy did not attenuate leptin's ability to restore euglycemia in diabetic rats. These results suggest that leptin's powerful chronic CNS antidiabetic actions are mediated primarily via nonautonomic mechanisms.