๐ค Authors: Josimar Macedo de Castro, Alanis da Silva Melo, Beatriz Lima Silveira, Igor Antรดnio Souza Martins, Maielli Martins Marรงal, Tenille Dal Bosco, Melina Belรฉn Keingeski, Elisa Carolina Lange de Oliveira, Mario Reis Alvares-da-Silva, Patrick Tรผrck, Alex Sander da Rosa Araujo, Layane Ramos Ayres, Lucas Stahlhรถfer Kowalewski, Mariana Kras Borges Russo, Mauricio Krause, Dirson Joรฃo Stein, Iraci L S Torres
Oral apigenin prevents obesity-related muscular atrophy, but not obesity itself, in middle-aged rats fed a high-calorie diet.
Obesity constitutes a growing global health concern, affecting individuals during the aging process. Flavonoids that increase tissue NAD+โฏlevels, such as apigenin (Api), are proposed for the treatment of obesity and age-related diseases.
Thus, this study aimed to provide initial preclinical evidence of Api in this setting using middle-aged rats induced to obesity by a high-calorie diet (HCD). Forty-seven 15-month-old male Wistar rats were assigned to five groups: standard diet (SD) or HCD, each with (Api at 50โฏmg/kg) or without treatment (vehicle), plus vehicle control group.
Obesity induction and therapeutic intervention were conducted concurrently for 88 days. Biometric, cardiac, adiposity, muscular, and blood biochemical parameters were analyzed.
Eighty-eight days post HCD rats had hyperglycemia, hypertriglyceridemia, increased visceral and subcutaneous fat, and heart hypertrophy, indicating obesity and related disorders (pโฏ<โฏ0.05 for all). The gastrocnemius of these rats exhibits reduced mass, smaller myocytes, and fibrosis (pโฏ<โฏ0.05), indicating sarcopenia, likely caused or worsened by obesity.
In parallel, preemptive Api treatment failed to prevent obesity and did not affect key adipose tissue browning genes, cardiac oxidative stress markers, or sirtuin and CD38 levels. However, it mitigated muscle loss and hypotrophy, in addition to elevating p70S6K levels in HCD-fed rats (pโฏ<โฏ0.05 for both).
These preclinical results suggest that although Api may not prevent some HCD-induced disturbances, it may attenuate age- and obesity-related atrophy via p70S6K anabolic signaling in middle-aged rats. To support clinical translation, particularly in sarcopenia subtypes, further mechanistic and therapeutic investigations on Api are required to elucidate its effects on skeletal muscle.
