title: AAV-mediated IL-10 gene transfer counteracts inflammation in the hypothalamic arcuate nucleus and obesity induced by high-fat diet.
abstract: Consumption of high-fat diet (HFD) induces energy imbalance and consequently obesity. In the pathogenesis of obesity, HFD triggers inflammation in the hypothalamus including arcuate nucleus (ARC). Interleukin-10 (IL-10) is a representative anti-inflammatory cytokine, known to ameliorate the adipose tissue inflammation and insulin resistance in obesity. However, the effect of IL-10 on the hypothalamic inflammation remains less defined. We here report the effect of over-expression of murine IL-10 using adeno-associated virus (AAV) vector on the inflammation in ARC and feeding behavior in HFD-induced obese (DIO) mice. DIO mice exhibited reduced POMC expression and elevated IKKs (IκB kinases) and SOCS3 expression in ARC. Overexpression of mIL-10 using AAV vector ameliorated obesity in parallel with restoration of ARC POMC expression in DIO mice. Moreover, IL-10 treatment suppressed IKKs activation and SOCS3 expression in ARC of DIO mice. These results suggest that IL-10 gene transfer provides an effective approach for counteracting HFD-induced inflammation and leptin resistance in ARC to prevent progression of obesity.
authors.affiliation: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan. Electronic address: nakata@jichi.ac.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakata
authors.affiliation: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Sawako
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Molecular and Medical Genetics, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okada
authors.affiliation: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan. Electronic address: tyada@jichi.ac.jp.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yada
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D000229:Dependovirus / Q000472:pathogenicity; D059305:Diet, High-Fat; D004435:Eating / Q000502:physiology; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics*; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D009765:Obesity / Q000139:chemically induced / Q000235:genetics*
chemical_list: D020738:Leptin; D016753:Interleukin-10
keywords: Arcuate nucleus; Feeding; IKK; IL-10; Inflammation; Leptin resistance; Obesity; POMC