Effects of a 12-week aerobic training on TLQP-21, its receptor, and UCP1 in STZ-induced diabetic Wistar rats.

Type 2 diabetes (T2DM) is marked by insulin resistance and impaired insulin production, with lifestyle interventions like exercise playing a key role in its management. TLQP-21, a vgf-derived peptide, and its receptor, C3AR1, are involved in regulating energy balance, insulin secretion, and inflammation. This study investigated the effects of a 12-week aerobic exercise intervention on TLQP-21/C3AR1 signaling in diabetic and non-diabetic Wistar rats. Animals were divided into four groups: Control (CG), Diabetic (DG), Exercise (EG), and Diabetic + Exercise (DEG). Diabetes was induced using a high-fat diet combined with streptozotocin (STZ) injection. Exercise training was implemented for 12 weeks, and tissues were collected for molecular and histological analysis. vgf mRNA expression did not change significantly in all tissues. However, TLQP-21 protein levels increased mainly in brown adipose tissue (BAT) and pancreas (PAN), particularly under diabetic and exercise conditions. Diabetes altered c3ar1 expression in a tissue-specific manner, decreasing hypothalamic (HPT) c3ar1 mRNA while increasing PAN c3ar1 mRNA and protein levels. Exercise attenuated diabetes-associated c3ar1 changes and also increased BAT UCP1 protein level. Exercise also improved BAT morphology by reducing brown adipocyte (BA) size and increasing BA and Mitochondria (MT) abundance. These findings suggest that exercise was associated with improved diabetic metabolic dysfunction by modulating TLQP-21/C3AR1 signaling, enhancing UCP1 expression, BAT remodeling, and mitochondrial abundance in rats, highlighting its therapeutic potential in managing metabolic dysfunctions associated with T2DM.