Obesity is associated with hypothalamic injury in rodents and humans.
Rodent models of obesity induced by consuming high-fat diet (HFD) are characterized by inflammation both in peripheral tissues and in hypothalamic areas critical for energy homeostasis. Here we report that unlike inflammation in peripheral tissues, which develops as a consequence of obesity, hypothalamic inflammatory signaling was evident in both rats and mice within 1 to 3 days of HFD onset, prior to substantial weight gain. Furthermore, both reactive gliosis and markers suggestive of neuron injury were evident in the hypothalamic arcuate nucleus of rats and mice within the first week of HFD feeding. Although these responses temporarily subsided, suggesting that neuroprotective mechanisms may initially limit the damage, with continued HFD feeding, inflammation and gliosis returned permanently to the mediobasal hypothalamus. Consistent with these data in rodents, we found evidence of increased gliosis in the mediobasal hypothalamus of obese humans, as assessed by MRI. These findings collectively suggest that, in both humans and rodent models, obesity is associated with neuronal injury in a brain area crucial for body weight control.
Division of Metabolism, Endocrinology and Nutrition, Diabetes and Obesity Center of Excellence, University of Washington, Seattle, Washington 98109, USA.
Joshua P
JP
Thaler
Chun-Xia
CX
Yi
Ellen A
EA
Schur
Stephan J
SJ
Guyenet
Bang H
BH
Hwang
Marcelo O
MO
Dietrich
Xiaolin
X
Zhao
David A
DA
Sarruf
Vitaly
V
Izgur
Kenneth R
KR
Maravilla
Hong T
HT
Nguyen
Jonathan D
JD
Fischer
Miles E
ME
Matsen
Brent E
BE
Wisse
Gregory J
GJ
Morton
Tamas L
TL
Horvath
Denis G
DG
Baskin
Matthias H
MH
Tschöp
Michael W
MW
Schwartz
D000293:Adolescent; D000328:Adult; D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D005911:Gliosis / Q000209:etiology / Q000473:pathology; D006801:Humans; D007031:Hypothalamus / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction; D013997:Time Factors; D055815:Young Adult
D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger