Background Obesity and aging are increasing globally and are known to be associated with adipose tissue and vascular stiffness, which are emerging as risk factors for the development of cardiometabolic and neurodegenerative diseases such as atherosclerosis, hypertension, type 2 diabetes mellitus (T2DM), metabolic syndrome, and Alzheimer’s disease. Therefore, we wished to test the hypothesis that the descending thoracic aorta may demonstrate aberrant ultrastructural remodeling that is ameliorated by empagliflozin, a sodium/glucose cotransporter 2 (SGLT2) inhibitor.
Methods Ten-week-old female wild-type control (C57BLKS/J) and db/db (BKS.Cg-Dock7m+/+Leprdb/J) mice were divided into three groups: lean untreated controls (CKC, n= 6), untreated db/db controls (DBC, n= 6) and DBC treated with empagliflozin (EMPA treated with 10 mg/kg/day for 10 weeks) (DBE, n= 6).
Results This study focuses on ultrastructural remodeling of tunica adventitia and tunica adiposa (periadventitial adipose tissue) of the descending aorta in both DBC and DBE mice. In DBC mice (untreated db/db controls), major observational remodeling included differentiation from thermogenic brown adipose tissue to white adipose tissue with hypertrophy of white adipocytes; ruptured plasma membranes and liberation of toxic lipids into the matrix, which incited inflammation with mast cells and macrophages. These changes were ameliorated in DBE mice (DBC treated with empagliflozin).
Conclusion Aberrant ultrastructural findings in DBC versus CKC and the amelioration with EMPA may provide better understanding how obesity and T2DM promote increased risk of vascular stiffness; a milieu for developing cardiovascular disease and target end-organ damage including nerve, retina, kidney and brain. Additionally, these findings may help us to better understand why obesity and T2DM result in the loss of homeostatic anticontractile function of tunica adiposa.
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