Influence of dietary fats on c-Fos-like immunoreactivity in mouse hypothalamus

The hypothalamus is a brain region of major importance in regulation of ene rgy balance via autonomic nervous control of both intake and expenditure. T here is substantial evidence that diets high in saturated fats lead to obes ity while diets equally high in polyunsaturated fats (PUFAs) do not. Using c-Fos as a marker, this study aimed to investigate hypothalamic neuronal re sponse in mice fed high fat diets (58% of calories as fat) emphasising satu rated, n - 3 or n - 6 polyunsaturated fatty acids, or a low fat (10% of cal ories) diet over periods of 1 and 7 weeks. In addition, a 4-week "reversal" intervention with n - 3 polyunsaturated or low fat diet was undertaken in saturated fat-fed mice. Food intake and body weight were measured over the feeding periods. at 1, 7 and 11 weeks mice were killed, epididymal fat pad were weighed and brains were removed for quantitation of hypothalamic c-Fos -like immunoreactive (FLI) neurons. Weight gain, and epididymal fat pad wei ght, were highest on the saturated fat diet and lowest on the n - 3 diet de spite similar food intakes (epididymal fat weight at week 7: saturated fat, 622 +/- 48 mg; n - 6 fat 422 +/- 69; low fat 387 +/- 10, n - 3 fat 225 +/- 26). Compared to a low fat diet, FLI neurons in the dorsal part of lateral hypothalamic (dLH) area was dramatically increased by saturated fat feedin g (+ 367% at 1 week) while ventromedial hypothalamic (VMH) activity was dec reased. In contrast with it - 6 and n - 3 feeding dLH Fl;I neuronal activit y was unchanged but actually increased in the VMH. Paraventricular nucleus (PVN) FLI neurons increased in the high saturated group only at 7 and ii we eks, after substantial fat accumulation. Substitution of saturated far diet with the n - 3 diet partially reversed (48%) the increase in FLI neurons i n PVN of saturated fat-fed mice, while it significantly increase FLI neuron s in arcuate nucleus (+400%). In summary, this study demonstrates that diet ary saturated fat modulates hypothalamic neuronal activity in a pattern (hi gh lateral, reduced ventromedial activity) consistent with its obesogenic e ffects. In contrast, diets equally high in PUFA (particularly of the n - 3 class) neither increase adiposity nor derange the lateral/medial neuronal a ctivity balance. (C) 1999 Elsevier Science B.V. All rights reserved.