Brain ACE2 overexpression stimulates food intake and promotes glucose intolerance in mice (1126.15)

Abstract

The brain Renin‐Angiotensin System (RAS) plays an important role in the regulation of metabolic function. While ACE2 has been reported to modulate brain RAS activity, its role in the central regulation of metabolism is unknown. To determine the role of central ACE2 in metabolism, Body weight and intake behaviors, assessed using metabolic cages, were measured in 24 wk old non‐transgenic (NT, n=8) and transgenic mice overexpressing ACE2 in the brain (SA, n=8). Fasting blood glucose was measured after a 14 h overnight fasting. Glucose tolerance test was performed by measuring blood glucose at 15, 30, 60 and 120 min after IP injection of glucose (2 g/kg). Plasma insulin level was measured by ELISA. Interestingly, body weight was significantly higher in SA than NT mice (39±1.5 vs. 31±0.8 g, P<0.05). In addition, SA mice exhibited increased daily food intake (0.12±0.01 vs. 0.09±0.01 g/g body weight), water intake (0.14±0.01 vs. 0.08±0.01 ml/g body weight), fasting blood glucose (147.8±13 vs.106.5±7 mg/dl), impaired glucose tolerance (AUC: 51.6±2 vs.41.5±1.7) and increased plasma insulin level (5.5±1.2 vs.1.7±0.3 ng/ml), compared to NT mice (P<0.05). These data suggest that ACE2 is involved in the central regulation of energy and glucose homeostasis. Brain ACE2 over‐expression leads to increased body weight, fasting glycemia and glucose intolerance, possibly through stimulating energy intake and insulin resistance.Grant Funding Source: Supported by NIH (NIGMS)