AAV-mediated IL-10 gene transfer counteracts inflammation in the hypothalamic arcuate nucleus and obesity induced by high-fat diet. (April 2017)

• Record Type: Journal Article
• Authors: Nakata, Masanori; Yamamoto, Sawako; Okada, Takashi; Yada, Toshihiko
• Is Part Of: Neuropeptides. Volume 62(2017)
• Page Start: 87
• Page End: 92
• Publication Date: 2017-04
• Subjects: POMC pro-opiomelanocortin -- AAV adeno-associated virus -- IKK IκB kinase -- ARC arcuate -- HFD high fat diet -- DIO diet-induced obesity -- SOCS suppressor of cytokine signaling; IL-10 -- IKK -- Arcuate nucleus -- POMC -- Inflammation -- Feeding -- Leptin resistance -- Obesity; Neuropeptides -- Periodicals; Neuropeptides; Neuropeptides -- Périodiques; Neuropeptides; Electronic journals; Periodicals; 572.65
• DOI: 10.1016/j.npep.2016.11.009
• Languages: English
• ISSNs: 0143-4179

Abstract

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. Highlights: AAV-mediated IL-10 gene transfer ameliorates obesity and hyperphagia in DIO mice. IL-10 gene transfer ameliorates impaired POMC expression and leptin resistance in DIO mice. IL-10 gene transfer ameliorates inflammatory IKK hyperactivity in hypothalamic ARC in DIO mice.