Endocrine Abstracts

Hypophagia and increased energy expenditure under inflammatory condition, such as observed after bacterial lipopolysaccharide (LPS) administration, are associated with activation of JAK2–STAT3 signaling in the CNS. High fat diet (HFD) is known to induce hypothalamic resistance to leptin signaling mediated by JAK2–STAT3 pathway. In this study we investigated the expression of p-STAT3 in the hypothalamus and brainstem of HFD treated animals under LPS (100 μg/kg) stimulation. Wistar rats fed standard/low-fat diet (3.95 kcal/g) or HFD (6.3 kcal/g) for 8 weeks were assigned into control diet-saline, control diet-LPS, HFD-saline and HFD-LPS groups. LPS reduced feeding in the control diet, but not in the HFD group. In control diet fed rats, LPS increased the STAT3 phosphorylation in the arcuate nucleus and ventromedial hypothalamic nucleus, but not in the HFD group. HFD per se increased p-STAT3 in the ARC with no further activation after LPS. Differently to the hypothalamic response, LPS increased p-STAT3 in the nucleus of the solitary tract (NTS) and raphe pallidus both in control diet and HFD fed groups, although this response was lower in the latter group. Despite not affecting food intake, LPS decreased body weight in HFD rats, which was associated with increased number of Fos and Fos/TH neurons in the NTS, and HFD-LPS showed higher number of activated noncatecholaminergic and catecholaminergic neurons in the NTS, compared with control diet-LPS group. In conclusion, our data indicate that LPS activates STAT3 mediated pathway in the hypothalamus and brainstem, leading to hypophagia, however acute effects of LPS on food intake, but not body weight loss, is abolished in HFD leptin resistant rats. Despite the absence of hypophagic effect, acute LPS under HFD induced body weight loss with higher brainstem neuron activation, suggesting that resistance to acute LPS effects under HFD might be selective to the hypothalamus.