Oral apigenin prevents obesity-related muscular atrophy, but not obesity itself, in middle-aged rats fed a high-calorie diet - 20/07/25
Abstract |
Obesity constitutes a growing global health concern, affecting individuals during the aging process. Flavonoids that increase tissue NAD+ levels, 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 50 mg/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 (p < 0.05 for all). The gastrocnemius of these rats exhibits reduced mass, smaller myocytes, and fibrosis (p < 0.05), 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 (p < 0.05 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.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Middle-aged rats were exposed to a high-calorie diet (HCD; 5.35 kcal/g) rich in saturated fat (8 % w/w, from lard) and sucrose (12 % w/w) for 88 days (starting with 15-month-old animals and ending at 18 months of age). Concurrently, apigenin (Api; 50 mg/kg) or its vehicle (Veh; hazelnut cream, 1 g/kg) was administered orally as a preemptive therapeutic intervention. As general results, HCD markedly increased body weight and total adiposity, accompanied by elevated serum triglyceride levels, cardiac hypertrophy, and reduced gastrocnemius muscle mass, indicative of obesity, dyslipidemia, left ventricular hypertrophy, and pre-sarcopenia, respectively. Regarding Api treatment, the main findings indicate that, although it did not prevent the development of obesity or related alterations such as cardiac remodeling, it attenuated hypertriglyceridemia, preserved skeletal muscle mass, and prevented the reduction in muscle fiber cross-sectional area in rats fed with HCD. Specifically concerning skeletal muscle, Api increased total p70 ribosomal S6 kinase (p70S6K) levels in the gastrocnemius muscle, suggesting a potential mechanism underlying its beneficial effects on this tissue.
Middle-aged rats were exposed to a high-calorie diet (HCD; 5.35 kcal/g) rich in saturated fat (8 % w/w, from lard) and sucrose (12 % w/w) for 88 days (starting with 15-month-old animals and ending at 18 months of age). Concurrently, apigenin (Api; 50 mg/kg) or its vehicle (Veh; hazelnut cream, 1 g/kg) was administered orally as a preemptive therapeutic intervention. As general results, HCD markedly increased body weight and total adiposity, accompanied by elevated serum triglyceride levels, cardiac hypertrophy, and reduced gastrocnemius muscle mass, indicative of obesity, dyslipidemia, left ventricular hypertrophy, and pre-sarcopenia, respectively. Regarding Api treatment, the main findings indicate that, although it did not prevent the development of obesity or related alterations such as cardiac remodeling, it attenuated hypertriglyceridemia, preserved skeletal muscle mass, and prevented the reduction in muscle fiber cross-sectional area in rats fed with HCD. Specifically concerning skeletal muscle, Api increased total p70 ribosomal S6 kinase (p70S6K) levels in the gastrocnemius muscle, suggesting a potential mechanism underlying its beneficial effects on this tissue.Le texte complet de cet article est disponible en PDF.
Highlights |
• | An 88 days high-calorie diet induces obesity and muscular atrophy in middle-aged rats. |
• | Oral apigenin does not prevent weight gain and body fat in middle-aged rats. |
• | Api prevents diet-induced skeletal muscle loss in obese animals. |
• | Api upregulates p70S6K levels in skeletal muscle, a key anabolic enzyme. |
• | Api emerges as a therapeutic alternative for musculoskeletal diseases like sarcopenia. |
Keywords : Obesity, Aging, Skeletal muscle, High-calorie diet, Middle-aged rats, Flavonoids, Apigenin
Plan
Vol 189
Article 118342- août 2025 Retour au numéro
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