High-fat diet induces site-specific unresponsiveness to LPS-stimulated STAT3 activation in the hypothalamus

Author:

de Carvalho Borges Beatriz1,Rorato Rodrigo1,Uchoa Ernane Torres1,Marangon Paula1,da Silva Glauber S. F.12,de Paula Francisco José3,Branco Luiz G. S.2,Antunes-Rodrigues José1,Elias Lucila Leico Kagohara1

Affiliation:

1. Department of Physiology and

2. Department of Morphology, Physiology and Basic Pathology, Dental School of Ribeirao Preto, University of Sao Paulo, Brazil

3. Department of Internal Medicine, School of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil; and

Abstract

Hypophagia induced by inflammation is associated with Janus kinase (JAK)-2/signal transducer and activator of transcription (STAT) 3 signaling pathway, and leptin-mediated hypophagia is also mediated by JAK2-STAT3 pathway. We have previously reported that lipopolysaccharide (LPS) did not reduce food intake in leptin-resistant high-fat diet (HFD) rats but maintained body weight loss. We investigated whether changes in p-STAT3 expression in the hypothalamus and brain stem could account for the desensitization of hypophagia in HFD animals after a low LPS dose (100 μg/kg). Wistar rats fed standard diet (3.95 kcal/g) or HFD (6.3 kcal/g) for 8 wk were assigned into control diet-saline, control diet-LPS, HFD-saline, and HFD-LPS groups. LPS reduced feeding in the control diet but not HFD. This group showed no p-STAT3 expression in the paraventricular nucleus (PVN) and ventromedial hypothalamic nucleus (VMH), but sustained, though lower than control, p-STAT3 in the nucleus of the solitary tract (NTS) and raphe pallidus (RPa). LPS decreased body weight in HFD rats and increased Fos expression in the NTS. LPS increased body temperature, oxygen consumption, and energy expenditure in both control diet and HFD rats, and this response was more pronounced in HFD-LPS group. Brown adipose tissue (BAT) thermogenesis and increased energy expenditure seem to contribute to body weight loss in HFD-LPS. This response might be related with increased brain stem activation. In conclusion, LPS activates STAT3-mediated pathway in the hypothalamus and brain stem, leading to hypophagia, however, LPS effects on food intake, but not body weight loss, are abolished by leptin resistance induced by HFD. The preserved STAT3 phosphorylation in the brain stem suggests that unresponsiveness to LPS on STAT3 activation under HFD might be selective to the hypothalamus.

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology

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