Aerobic exercise promotes the functions of brown adipose tissue in obese mice via a mechanism involving COX2 in the VEGF signaling pathway

Pengyu Fu,Pengyu Fu,Rongxin Zhu,Rongxin Zhu,Yang Hu,Chengjun Wu,Lijing Gong,Hans-Christer Holmberg,Jie Jia,Pawel Cieszczyk

doi:10.1186/s12986-021-00581-0

Abstract

BackgroundHigh-fat diet (HFD)-induced obesity causes immune cells to infiltrate adipose tissue, leading to chronic inflammation and metabolic syndrome. Brown adipose tissue (BAT) can dissipate the energy produced by lipid oxidation as heat, thereby counteracting obesity. Aerobic exercise activates BAT, but the specific underlying mechanism is still unclear.MethodsMale C57BL/6 J mice were divided into a normal diet control group (NC group) and HFD group (H group). After becoming obese, the animals in the H group were subdivided into a control group (HC group) and an exercise group (HE group, with treadmill training). After 4 weeks, the mRNA profile of BAT was determined, and then differentially expressed key genes and pathways were verified in vitro.ResultsRelative to the NC group, the genes upregulated in the HC group coded mainly for proteins involved in immune system progression and inflammatory and immune responses, while the downregulated genes regulated lipid metabolism and oxidation–reduction. Relative to the HC group, the genes upregulated in the HE group coded for glycolipid metabolism, while those that were downregulated were involved in cell death and apoptosis. VEGF and other signaling pathways were enhanced by aerobic exercise. Interaction analysis revealed that the gene encoding cyclooxygenase 2 (COX2) of the VEGF signaling pathway is central to this process, which was verified by a sympathetic activator (isoprenaline hydrochloride) and COX2 inhibitor (NS-398).ConclusionsIn mice with HFD-induced obesity, four weeks of aerobic exercise elevated BAT mass and increased the expression of genes related to glycolipid metabolism and anti-inflammatory processes. Several pathways are involved, with COX2 in the VEGF signaling pathway playing a key role.

Highlights

High-fat diet (HFD)-induced obesity causes immune cells to infiltrate adipose tissue, leading to chronic inflammation and metabolic syndrome
After the 4-week intervention, the HC group had less Brown adipose tissue (BAT) mass percentage [(BAT mass/BF) %] than the NC group, while the HE group had less than the NC group but significantly more than the HC group (P < 0.05) (Fig. 2f )
After the 4-week intervention, the protein expression of uncoupling protein 1 (UCP1) in the BAT of the HC group was lower than the NC group (P < 0.05), and the HE group tended to have more UCP1 than the HC group, this difference was not statistically significant (Fig. 2g)

Summary

Introduction

High-fat diet (HFD)-induced obesity causes immune cells to infiltrate adipose tissue, leading to chronic inflammation and metabolic syndrome. Obesity characterized by increased adipocyte size and excessive accumulation of fat, has become one of the major risk factors for metabolic syndrome (MS) [1]. Obesity induced by a high-fat diet (HFD), the major environmental cause of this condition [2], leads to immune cell infiltration into white adipose tissue (WAT). Obesity might influence BAT, including reducing its thermogenic activity and capacity to utilize free fatty acids (FFAs) [6].

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Discussion

Conclusion