Lycopene Improves Bone Quality and Regulates AGE/RAGE/NF-кB Signaling Pathway in High-Fat Diet-Induced Obese Mice.

Bingke Xia,Fangfang Mo,Beibei Chen,Xuan Dai,Xiang-Dong Wang,Yage Liu,Dandan Zhao,Ruyuan Zhu,Xinxiang Wang,Zimengwei Ye,Sihua Gao,Lili Wang,Dieter Bromme,Hao Zhang,Dongwei Zhang,Dragan Hrnčić

doi:10.1155/2022/3697067

Abstract

Objective This study was aimed at examining the effects of lycopene on bone metabolism in high-fat diet (HFD)- induced obese mice and to identify the potential underlying mechanisms. Methods Mice were fed a HFD for 12 weeks and then continue with or without lycopene intervention (15 mg/kg) for additional 10 weeks. The effects of lycopene on blood glucose and lipid metabolism, as well as serum levels of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and malondialdehyde (MDA) were determined by biochemical assays. Bone histomorphological features and osteoclast activity were assessed by hematoxylin/eosin and tartrate-resistant acid phosphatase staining. Bone microstructure at the proximal tibial metaphysis and diaphysis was determined by microcomputed tomography. Tibial biomechanical strength and material profiles were measured by a three-point bending assay and Fourier transform infrared spectroscopy. Protein expressions involved in the AGE/RAGE/NF-кB signaling pathway were determined by western blot and/or immunohistochemical staining. Results Lycopene consumption reduced body weight gain and improved blood glucose and lipid metabolism in HFD-induced obese mice. In addition, lycopene treatment preserved bone biomechanical strength, material profiles, and microarchitecture in obese mice. Moreover, these alterations were associated with an increase in serum levels of T-AOC and SOD, and a decline in serum levels of MDA, as well as a reduction of AGEs, RAGE, cathepsin K, and p-NF-кBp65 and NF-кBp65 expressions in the femurs and tibias of obese mice. Conclusion Lycopene may improve bone quality through its antioxidant properties, which may be linked with the regulation of the AGE/RAGE/NF-кB signaling pathway in obese mice. These results suggest that lycopene consumption may be beneficial for the management of obesity-induced osteoporosis.

Highlights

As a metabolically active tissue, bone is regulated by systemic glucose and lipid metabolism [1]
At the 22nd week, the body weight of the mice in the high-fat diet (HFD)-C group increased by ~33% compared to that in the Normal control (NC) group
There were significant negative correlations between BV/TV, Tb.N, BMD of tibial diaphysis, and MDA. These results suggested that blood glucose and lipid metabolism could affect bone quality

Summary

Introduction

As a metabolically active tissue, bone is regulated by systemic glucose and lipid metabolism [1]. Given the worldwide prevalence of obesity and hyperglycemia, the study of bone metabolism has gained increasing attention [2–4]. Accumulating evidence suggests that sustained dyslipidemia and hyperglycemia impair bone microstructure, material compositions, and biomechanical strength, leading to an increased risk of bone fractures [5–7]. Clinical studies revealed that bone quality is mostly neglected during obesity management [8, 9]. Current pharmacological countermeasures for obesity and osteoporosis are associated with poor adherence and adverse complications [10].

Methods

Results

Conclusion