It has been widely suggested that saturated fat consumption has fuelled the current
obesity epidemic. Macronutrient choices appear to be important not only as potential factors influencing
obesity, but also independently as risk factors for diabetes,
cardiovascular disease and
cancer. The
neuropeptide galanin has previously been implicated in the regulation of fat intake, although its precise role has been contested. The present study investigated mice with targeted knockout of the
galanin gene (GKO). We demonstrate that, when only a high fat diet (HFD) was available, wild-type (WT) animals consumed significantly more energy than the GKO mice (89.85 +/- 4.57 kJ/day versus 76.84 +/- 3.55 kJ/day, P < 0.001, n = 17 versus 15). Consistent with this, WT animals gained more
body weight when fed the HFD than GKO animals (3.48 +/- 0.44 g versus 2.02 +/- 0.62 g, P < 0.001, n = 17 versus 15). In a macronutrient choice scenario, WT mice ate almost three-fold more fat than GKO animals (0.63 +/- 0.02 g versus 0.23 +/- 0.01 g, P < 0.001, n = 18 versus 24). Chronic administration of
galanin by mini-osmotic pumps into the lateral ventricle of GKO animals partially reversed the fat avoidance phenotype. Fat intake was significantly lower in the
phosphate-buffered saline-treated GKO group compared to
galanin-treated GKO animals (0.32 +/- 0.01 g versus 0.38 +/- 0.01 g, P < 0.005, n = 17 versus 17). These data are compatible with the hypothesis that
galanin specifically regulates fat intake, and implies that an antagonist to one or more of the
galanin receptor subtype(s) may be of use in the treatment of some forms of
obesity.