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

Abstract

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 WT → WT 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, HFD-induced insulin resistance was correlated with the status of WAT inflammation and comparable between WT → Pfkfb3+/- mice and WT → WT 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.

• Authors: Hang Xu, Bilian Zhu, Honggui Li, Boxiong Jiang, Yina Wang, Qiongli Yin, James Cai, Shannon Glaser, Heather Francis, Gianfranco Alpini, Chaodong Wu
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 95 Pg. 108764 (09 2021) ISSN: 1873-4847 [Electronic] United States
• PMID: 33964465 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Cytokines
• Dietary Fats
• Fatty Acids, Monounsaturated
• palmitoleic acid
• PFKFB3 protein, mouse
• Phosphofructokinase-2

Topics

• Adipocytes, White (metabolism)
• Adipose Tissue (metabolism, pathology)
• Adoptive Transfer
• Animals
• Cells, Cultured
• Cytokines (genetics, metabolism)
• Diet, High-Fat (adverse effects)
• Dietary Fats (administration & dosage, pharmacology)
• Fatty Acids, Monounsaturated (metabolism)
• Gene Expression Regulation, Enzymologic (drug effects)
• Glucose Intolerance
• Inflammation (metabolism)
• Insulin Resistance
• Macrophages (physiology)
• Male
• Mice
• Phosphofructokinase-2 (genetics, metabolism)
• Signal Transduction