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

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 LXR alpha 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-Erb alpha from the YHFD + AGE group; RAGE, OST48, CLOCK, BMAL1, and Rev-Erb alpha 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-alpha 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-Erb alpha from three intervention groups were increased, while p-Aktser473 from the MAHFD and MAHFD + AGE groups was decreased and PPAR alpha 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-alpha gene expressions from three intervention groups were increased, while BMAL1 from the MAHFD + AGE and MAEX groups; PPAR gamma 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.