Adipose transplantation improves metabolism and atherosclerosis but not PVAT abnormality or vascular dysfunction in lipodystrophic Seipin/Apoe null mice

Adipose dysfunction in lipodystrophic SEIPIN deficiency is associated with multiple metabolic disorders and increased risks of developing cardiovascular diseases, such as atherosclerosis, cardiac hypertrophy, and heart failure. Recently, adipose transplantation is found to correct adipose dysfunction and metabolic disorders in lipodystrophic Seipin knockout mice; however, whether adipose transplantation could improve lipodystrophy-associated cardiovascular consequences is still unclear. Here, we aimed to explore the effects of adipose transplantation on lipodystrophy-associated metabolic cardiovascular diseases in Seipinknockout mice crossed into atherosclerosis-prone apolipoprotein E (Apoe) knockout background. At two months of age, lipodystrophic Seipin/Apoe double knockout mice and non-lipodystrophic Apoe knockout controls were subjected to adipose transplantation or sham operation. Seven months later, mice were sacrificed. Our data showed that although adipose transplantation had no significant impact on the endogenous adipose atrophy or gene expression, it remarkably increased plasma Leptin but not Adiponectin concentration in Seipin/Apoe double knockout mice. This led to significantly reduced hyperlipidemia, hepatic steatosis, and Insulin resistance in Seipin/Apoe double knockout mice. Consequently, atherosclerosis burden, intraplaque macrophage infiltration, and aortic inflammatory gene expression were all attenuated in Seipin/Apoe double knockout mice with adipose transplantation. However, adipocyte morphology, macrophage infiltration, or fibrosis of the perivascular adipose tissue were not altered in Seipin/Apoe double knockout mice with adipose transplantation, followed by no significant improvement of vasoconstriction or relaxation. In conclusion, we demonstrate that adipose transplantation could alleviate lipodystrophy-associated metabolic disorders and atherosclerosis, but has an almost null impact on perivascular adipose abnormality or vascular dysfunction in lipodystrophic Seipin/Apoe double knockout mice.

Adipose Transplantation; Atherosclerosis; Lipodystrophy; Metabolism; SEIPIN.