High-fat diet induces site-specific unresponsiveness to LPS-stimulated STAT3 activation in the hypothalamus.
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.
Department of Physiology and.
Beatriz de Carvalho
Bde C
Borges
Rodrigo
R
Rorato
Ernane Torres
ET
Uchoa
Paula
P
Marangon
Glauber S F
GS
da Silva
Francisco José
FJ
de Paula
Luiz G S
LG
Branco
José
J
Antunes-Rodrigues
Lucila Leico Kagohara
LL
Elias
D000818:Animals; D001835:Body Weight / Q000502:physiology; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000378:metabolism; D004435:Eating / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D004041:Dietary Fats; D020738:Leptin; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat
Fos; body temperature; high-fat diet; indirect calorimetry; lipopolysaccharide; phospho-STAT3; uncoupling protein-1