Abstract
Evidence from human studies and transgenic mice lacking the type 3 adenylyl cyclase (AC3) indicates that AC3 plays a role in the regulation of body weight. It is unknown in which brain region AC3 exerts such an effect. We examined the role of AC3 in the hypothalamus for body weight control using a floxed AC3 mouse strain. Here, we report that AC3 flox/flox mice became obese after the administration of AAV-CRE-GFP into the hypothalamus. Both male and female AC3 floxed mice showed heavier body weight than AAV-GFP injected control mice. Furthermore, mice with selective ablation of AC3 expression in the ventromedial hypothalamus also showed increased body weight and food consumption. Our results indicated that AC3 in the hypothalamus regulates energy balance.
Highlights
Obesity is a major health issue associated with complications that cause significant morbidity and mortality
It has been reported that AC3 gene polymorphisms are associated with obesity in a group of Swedish men [7]
We verified that AC3 expression in the hypothalamus was reduced when AAV1-CRE-GFP was injected into the hypothalamus of floxed AC3 mice using a ployclonal antibody against AC3 (Figure 2)
Summary
Obesity is a major health issue associated with complications that cause significant morbidity and mortality. The association signal at AC3 is apparently driven by a miss-sense variant [8]. These human genetic studies suggested that AC3 might play an important role in the regulation of body weight. Previous studies from our lab showed that a global AC3 mouse knockout exhibit adult onset obesity [9]. They show increased fat mass, larger adipocytes, reduced physical activity, increased food consumption, and leptin insensitivity. It was discovered that a gain of function mutation in AC3 protects mice from diet-induced obesity providing further evidence that AC3 may play a major role in weight control [10].
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