Nesfatin-130−59 Injected Intracerebroventricularly Differentially Affects Food
Intake Microstructure in Rats Under Normal Weight and Diet-Induced Obese
Conditions
Nesfatin-1 is well-established to induce an anorexigenic effect. Recently,
nesfatin-130−59, was identified as active core of full length nesfatin-11−82
in mice, while its role in rats remains unclear. Therefore, we investigated
the effects of nesfatin-130−59 injected intracerebroventricularly (icv) on the
food intake microstructure in rats. To assess whether the effect was also
mediated peripherally we injected nesfatin-130−59 intraperitoneally (ip).
Since obesity affects the signaling of various food intake-regulatory peptides
we investigated the effects of nesfatin-130−59 under conditions of diet-
induced obesity (DIO). Male Sprague–Dawley rats fed ad libitum with standard
diet were icv cannulated and injected with vehicle (5 μl ddH2O) or
nesfatin-130−59 at 0.37, 1.1, and 3.3 μg (0.1, 0.3, 0.9 nmol/rat) and the food
intake microstructure assessed using a food intake monitoring system. Next,
naïve rats were injected ip with vehicle (300 μl saline) or nesfatin-130−59
(8.1, 24.3, 72.9 nmol/kg). Lastly, rats were fed a high fat diet for 10 weeks
and those developing DIO were icv cannulated. Nesfatin-1 (0.9 nmol/rat) or
vehicle (5 μl ddH2O) was injected icv and the food intake microstructure
assessed. In rats fed standard diet, nesfatin-130−59 caused a dose-dependent
reduction of dark phase food intake reaching significance at 0.9 nmol/rat in
the period of 4–8 h post injection (−29%) with the strongest reduction during
the fifth hour (−75%), an effect detectable for 24 h (−12%, p < 0.05 vs.
vehicle). The anorexigenic effect of nesfatin-130−59 was due to a reduction in
meal size (−44%, p < 0.05), while meal frequency was not altered compared to
vehicle. In contrast to icv injection, nesfatin-130−59 injected ip in up to
30-fold higher doses did not alter food intake. In DIO rats fed high fat diet,
nesfatin-130−59 injected icv reduced food intake in the third hour post
injection (−71%), an effect due to a reduced meal frequency (−27%, p < 0.05),
while meal size was not altered. Taken together, nesfatin-130−59 is the active
core of nesfatin-11−82 and acts centrally to reduce food intake in rats. The
anorexigenic effect depends on the metabolic condition with increased
satiation (reduction in meal size) under normal weight conditions, while in
DIO rats satiety (reduction in meal frequency) is induced