Effects of Voluntary Exercise on Liver and Adipose Tissue Dysfunction in Both Young and Middle‐Aged Mice Fed a High‐Fat Diet Combined with Dietary Advanced Glycation End Products

Abstract

To determine whether voluntary exercise is capable of improving liver and adipose tissue dysfunction caused by the high‐fat diet (HFD) combined with dietary advanced glycation end products (AGEs). Young and middle‐aged male C57BL/6J mice were divided into the control group, HFD group, HFD combined AGE group (HFD + AGE), and combined diet with exercise group (HFD + AGE + EX). For young mice, in the liver tissue, compared to the YCON group, RAGE from the YHFD + AGE group and SREBP1 from the YHFD + AGE and YHFD + AGE + EX groups were increased, while LXRα from the YHFD YHFD + AGE, and YHFD + AGE + EX groups was decreased. In epididymal fat, CLOCK from the YHFD group; RAGE, OST48, BMAL1, and Rev‐Erbα from the YHFD + AGE group; RAGE, OST48, CLOCK, BMAL1, and Rev‐Erbα from the YHFD + AGE + EX group; SIRT1 from the YHFD + AGE group; adiponectin from the YHFD group; and ATGL from the YHFD and YHFD + AGE groups were significantly lower, while p‐HSLser660 from the YHFD + AGE group and p‐Aktser473 from the YHFD + AGE + EX group were significantly higher than in the YCON group. Additionally, IL‐10 and IL‐1Ra mRNA expressions from the YHFD and YHFD + AGE group were significantly decreased, while IL‐10 and IL‐1Ra from the YHFD + AGE + EX group and TNF‐α from the YHFD, YHFD + AGE, and YHFD + AGE + EX groups were significantly increased. For middle‐aged mice, in the liver tissue, compared to the MACON group, CLOCK and Rev‐Erbα from three intervention groups were increased, while p‐Aktser473 from the MAHFD and MAHFD + AGE groups was decreased and PPARα from the MAHFD and MAHFD + AGE groups was decreased. In epididymal fat, compared to the MACON group, RAGE from the MAHFD + AGE group; p‐Aktser473 from the MAHFD + AGE + EX group; and TNF‐α gene expressions from three intervention groups were increased, while BMAL1 from the MAHFD + AGE and MAEX groups; PPARγ and IL‐1Ra from the MAHFD + AGE group; SIRT1 from the MAHFD, MAHFD + AGE, and MAHFD + AGE + EX groups; adiponectin from the MAHFD group; and p‐HSLser660, ATGL, and IL‐10 from the MAHFD and MAHFD + AGE groups were decreased. In conclusion, HFD combined with AGE diet caused dysfunction in the liver and adipose glucolipid metabolism, especially in middle‐aged mice, and voluntary exercise reversed metabolic abnormalities to some extent with different mechanisms involved for young and middle‐aged mice.