Disruption of type 3 adenylyl cyclase expression in the hypothalamus leads to obesity

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.

Keywords: hypothalamus; obesity; type 3 adenylyl cyclase.

Figure 1

AC3 in the hypothalamus contributes to obesity. A. Representative mice at weeks 10 after AAV-GFP and AAV-GFP-CRE injections. B. Daily food consumption of AC3 lox/lox mice with AAV-GFP and AAV-GFP-CRE injections. C-D. Body weight in female (C), Male (D) mice after introhypothalamus injection of AAV-GFP and AAV-GFP-CRE.

Figure 2

The immunohisto chemistry showing AC3 (red) expression in the hypothalamus following AAV-GFP injection (A and B) and AAV-GFP-CRE injections (C and D), DAPI (blue), GFP (green) and AC3 (red). Injection site: AP −1.46 mm posterior to Bregma; ML ±0.5 mm; DV −5.0 & −5.5 mm.

Figure 3

The mice with specific ventromedial hypothalamus injection of AAV-GFP-CRE develop obesity. A. The body weight of AC3 lox/lox mice with VMH injection of AAV-GFP and AAV-GFP-CRE respectively. B. Daily food consumption of AC3 lox/lox mice after AAV-GFP and AAV-GFP-CRE injections.