The role of the phosphorylation of NF-kB, p65 subunit on fat metabolism

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670791
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Functional basic dentistry
• Research Institution: Kyushu Dental College
• Principal Investigator: JIMI Eijiro 九州歯科大学, 歯学部, 教授 (40276598)
• Co-Investigator(Kenkyū-buntansha): ONO Kentaro 九州歯科大学, 歯学部, 准教授 (40316154) ; FUKUSHIMA Hidefumi 福岡歯科大学, 歯学部, 准教授 (70412624) ; KATAOKA Shinji 九州歯科大学, 歯学部, 助教 (80364149)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: NF-kBのリン酸化 / 生活習慣病 / インスリン抵抗性

Outline of Final Research Achievements

The visceral fat accumulation is the common clinical condition of lifestyle-related diseases, such as, diabetes, the arteriosclerosis and the high blood pressure, which were caused by the chronic inflammation in fat. Recent reports showed that phosphorylation of p65, a main subunit of NF-κB involved in epigenetic regulation of gene expression. To better understand the biological role of the phosphorylation of p65 of serine at position 536 (in mouse at 534), we generated mice expressing a p65 mutant bearing an alanine instead of serine at position 534 (S534A) mice. After exposure for 5 weeks to high-fat diet (HFD), HFD increased fat mass in WT mice, with a statistically larger increase in S534A mice. HFD also produced a large increase in liver weight in S534A mice but not in WT mice. Insulin activates Akt in WT mouse embryonic fibroblasts but the phosphorylation of Akt was reduced in S534A MEFs. These results suggest that S534A mutants lead to insulin resistance.

Free Research Field

分子生物学