Diabetes mellitus (DM) is a global health problem. The prevalence of diagnosed and undiagnosed diabetes in the US is progressively increasing from 7.8% in 2007, 14.5% in 2010 and expected to rise between 24.7% to 32.8% in 2050. Diabetes is the most common cause of end stage renal disease, responsible for more than 40% of all cases in the US, and this number are likely to continue to increase unabated. Endothelial cell dysfunction is a central pathophysiological mechanism that contributes to diabetes and diabetic nephropathy (DN).

Acute kidney injury (AKI) and chronic kidney disease (CKD) are major contributors to overall morbidity andmortality in patients in the US. The overall objective of the proposed study is to establish untargeted andtargeted spatial metabolomics analysis of tissues from normal and diseased kidneys to assess cellularmetabolic states associated with healthy function, acute injury, chronic condition, and recovery.

Mitochondria in hepatocytes play a major role in maintaining whole-body energy metabolism and normalfunction of the liver. Impaired mitochondrial function is closely associated with various metabolic diseases suchas obesity, insulin resistance, and hepatosteatosis. However, the precise underlying mechanisms remain to befully elucidated.

Sodium-Glucose cotransport inhibitors (SGLT2i) are a novel class of antidiabetic agentswhich lower the plasma glucose concentration by inhibiting renal glucose reuptake andproducing glucosuria.

Obesity is a critical global epidemic, a leading cause of preventable death, and a source of skyrocketing healthcare costs. Currently more than two thirds of US adults are overweight and at least one third are consideredobese.