Adipocyte inducible 6-phosphofructo-2-kinase suppresses adipose tissue inflammation and promotes macrophage anti-inflammatory activation

被引：3

作者：

Xu, Hang ^{[1
]}

Zhu, Bilian ^{[1
,2
]}

Li, Honggui ^{[2
]}

Jiang, Boxiong ^{[2
]}

Wang, Yina ^{[2
]}

Yin, Qiongli ^{[2
]}

Cai, James ^{[3
]}

Glaser, Shannon ^{[4
]}

Francis, Heather ^{[5
,6
]}

Alpini, Gianfranco ^{[5
,6
]}

Wu, Chaodong ^{[1
]}

机构：

[1] Texas A&M Univ, Dept Nutr, College Stn, TX USA

[2] Sun Yat Sen Univ, Dept VIP Med Serv Ctr, Affiliated Hosp 3, Guangzhou, Guangdong, Peoples R China

[3] Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX USA

[4] Texas A&M Univ, Coll Med, Med Physiol, Bryan, TX USA

[5] Indiana Univ, Hepatol & Gastroenterol, Med, Indianapolis, IN 46204 USA

[6] Richard L Roudebush VA Med Ctr, Indianapolis, IN USA

来源：

JOURNAL OF NUTRITIONAL BIOCHEMISTRY | 2021年 / 95卷

关键词：

Pfkfb3; Adipocytes; Adipose tissue inflammation; Insulin resistance; Palmitoleate; RECEPTOR-GAMMA ACTIVATION; INSULIN-RESISTANCE; OXIDATIVE STRESS; PPAR-GAMMA; OBESITY; DISRUPTION; OVEREXPRESSION; POLARIZATION;

D O I：

10.1016/j.jnutbio.2021.108764

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Obesity-associated inflammation in white adipose tissue (WAT) is a causal factor of systemic insulin resistance. To better understand how adipocytes regulate WAT inflammation, the present study generated chimeric mice in which inducible 6-phosphofructo-2-kinase was low, normal, or high in WAT while the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (Pfkfb3) was normal in hematopoietic cells, and analyzed changes in high-fat diet (HFD)-induced WAT inflammation and systemic insulin resistance in the mice. Indicated by proinflammatory signaling and cytokine expression, the severity of HFD-induced WAT inflammation in WT -> Pfkfb3 + /- mice, whose Pfkfb3 was disrupted in WAT adipocytes but not hematopoietic cells, was comparable with that in W T -> W T mice, whose Pfkfb3 was normal in all cells. In contrast, the severity of HFD-induced WAT inflammation in WT -> Adi-Tg mice, whose Pfkfb3 was over-expressed in WAT adipocytes but not hematopoietic cells, remained much lower than that in WT -> WT mice. Additionally, HFDinduced insulin resistance was correlated with the status of WAT inflammation and comparable between WT -> Pfkfb3 + /- mice and W T -> W T mice, but was significantly lower in WT -> Adi-Tg mice than in WT -> WT mice. In vitro , palmitoleate decreased macrophage phosphorylation states of Jnk p46 and Nfkb p65 and potentiated the effect of interleukin 4 on suppressing macrophage proinflammatory activation. Taken together, these results suggest that the Pfkfb3 in adipocytes functions to suppress WAT inflammation. Moreover, the role played by adipocyte Pfkfb3 is attributable to, at least in part, palmitoleate promotion of macrophage anti-inflammatory activation. (c) 2021 Elsevier Inc. All rights reserved.

引用

页数：10