Age-related changes in adipose tissue metabolomics and inflammation, cardiolipin metabolism, and ferroptosis markers in an aged rat model

Abstract Aging adipose tissue shows elevated levels of inflammation, which can lead to age-related metabolic dysfunction. However, which metabolic changes in adipose tissue caused by aging are related to the occurrence of inflammation remain unclear. Therefore, we assessed the changes in metabolic phenotypes in the adipose tissue of 18 months adult sedentary (ASED) and 26 months old sedentary (OSED) rats compared with the tissue of 8 months young sedentary (YSED) rats used as the control group. Compared with YSED, ASED and OSED rats had increased body weight and Lee's index, and decreased grasp power and handing time. The expression of adipose tissue senescence-associated secretory phenotype (SASP) in the ASED and OSED groups was increased compared with that in the YSED group. The results of metabolomic studies showed increased levels of palmitic acid, elaidic acid, 1-heptadecanol, and α-tocopherol in the ASED and OSED groups compared with the YSED group, while sarcosine levels were decreased. Furthermore, stearic acid was specifically elevated in the ASED group. Cholesterol was upregulated, whereas linoleic acid and phosphate were specifically downregulated in the OSED group. The ASED group was associated with fatty acid biosynthesis and amino acid metabolism. In contrast, the OSED group was associated with fatty acid biosynthesis, steroid biosynthesis, amino acid metabolism, and linoleic acid metabolism. Additionally, increased levels of ferroptosis were found in both the ASED and OSED groups, whereas mitochondrial dysfunction due to abnormal cardiolipin metabolism was more pronounced in the OSED group. In conclusion, both the ASED and OSED can affect the lipid storage capacity of adipose tissue and oxidative stress leading to inflammation. Furthermore, OSED can further affect the metabolism of cardiolipin leading to abnormal mitochondrial function.