AOD is a peptide 15 amino acids long which mimics a small portion of the growth hormone that has the fat reducing effects (increases fat metabolism). It works by mimicking the way natural growth hormone regulates fat metabolism but without the adverse effects on blood sugar and growth that is seen if unmodified growth hormone is given. It stimulates lipolysis (break down of fat) and inhibits lipogenesis (non fat food being stored in the body as fat).
Following amplification, PCR products were electrophoresed on 1.3% agarose gels and transferred onto Hybond N+ membranes (RPN 303B, Amersham Pharmacia Biotech) by Southern blotting in 0.4 M NaOH/1 M NaCl. The membranes were rinsed for 5 min in 0.5 M Tris-HCl (pH 7.5)/1 M NaCl and then in 0.3 M NaCl/30 mM sodium citrate, and air dried. Membranes were apposed directly to a phosphor imager screen for 18 h, and scanned using a Storm PhosphorImager and data quantitated using MCID software (Imaging Research, Inc., St. Catherines, Ontario, Canada). The β3-AR product bands were normalized against the β-actin control, averaged, and RNA isolated from treated animals was expressed against control animals.
Prof. Gary Wittert, Adelaide-based Principal Investigator on the study, said: “As the world’s first drug with a metabolic mechanism of action AOD9604 could occupy a unique position among the options available to doctors for the management of obesity. It is pleasing that the invention and its development from the laboratory bench has been an all–Australian effort.”
Figure 1A shows the chronic effect of saline, AOD9604, and hGH in lean C57BL/6J mice on body weight and food intake. The hGH potently increased the body weight gain of these mice, reaching significance by d 8. There was an increase in body weight after AOD9604 only on the last day of treatment. In contrast, ob/ob mice (Fig. 1B) showed a profound decrease in body weight after both AOD9604 and hGH. Importantly, these effects were not attributed to changes in food intake in either the lean or the ob/ob mice (Fig. 1, C and D, respectively).
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