Nicotinamide riboside and resveratrol improve brown adipose tissue structure and metabolic dysfunction in Type 1 diabetic rats

Type 1 Diabetes Mellitus is associated with impaired energy metabolism and structural and functional alterations of brown adipose tissue (BAT). Targeting mitochondrial biogenesis and thermogenic pathways may represent an effective strategy to counteract Type 1 Diabetes -induced BAT atrophy. Nicotinamide riboside (NR) and resveratrol are known activators of NAD⁺/Sirt1 signaling with potential metabolic benefits. This study aimed to investigate the effects of NR and resveratrol, individually and in combination, on the structural, molecular, and metabolic characteristics of interscapular BAT in streptozotocin (STZ)-induced diabetic rats. Adult male Sprague-Dawley rats were treated with NR and/or resveratrol by oral gavage for two months. After one month of treatment, Type 1 Diabetes was induced using STZ. Fasting blood glucose and serum lipid profiles were assessed. BAT morphology was evaluated using unbiased stereological methods, and the expression of key thermogenic and mitochondrial genes (Ucp1, Pgc1α, Prdm16, Sirt1, Tfam, Nrf1, and Nrf2) was quantified by real-time PCR. STZ-induced Type 1 Diabetes resulted in severe hyperglycemia and dyslipidemia, accompanied by significant reductions in BAT volume, adipocyte number, vascularization, and the expression of thermogenic and mitochondrial regulatory genes. Treatment with NR or resveratrol significantly improved metabolic parameters and partially restored BAT structural and molecular alterations. Combined treatment with NR and resveratrol produced the most pronounced effects, nearly normalizing BAT stereological parameters, vascular organization, and thermogenic and mitochondrial-related gene expression, while markedly improving glucose and lipid profiles. NR and resveratrol exert protective and restorative effects on Type 1 Diabetes Mellitus -induced BAT atrophy, likely through activation of NAD⁺/Sirt1-mediated mitochondrial and thermogenic pathways. Combined therapy demonstrated synergistic benefits, suggesting a promising strategy for preserving BAT structure and function under diabetic conditions.