Physical inactivity and high-calorie diets are major drivers of obesity and metabolic disease. In a previous pilot study under physiological dietary conditions, Cimicifuga racemosa extract Ze 450 reduced visceral adiposity and leptin levels in female rats, suggesting exercise-like metabolic effects. Whether these effects persist under diet-induced metabolic stress remains unclear. This study investigated whether Ze 450 exerts exercise-associated metabolic effects in a high-fat (HF) diet model. Non-ovariectomized female Wistar rats (n = 30) were randomized to standard diet (SD), HF, HF + Ze 450 (130 mg/kg), HF + voluntary running activity, or HF + Ze 450 + activity (n = 6/group) for 12 weeks. Activity groups had nightly access to running wheels. Visceral fat mass, adipocyte morphology, glucose tolerance, serum leptin and cholesterol levels, and expression of metabolic genes (Fasn, Cebpa, Abca1, Cyp7a1) were assessed. HF feeding induced body weight gain, visceral fat accumulation, adipocyte hypertrophy, hyperleptinemia, and impaired glucose tolerance. Ze 450 treatment and running activity antagonized the HF-induced increases in body and visceral fat mass, attenuated HF diet-induced impairments in glucose handling, lowered leptin levels, and modulated metabolic gene expression. While the physiological effects of Ze 450 were comparable to exercise, molecular analyses revealed distinct regulatory patterns. Ze 450 mitigated key features of HF diet-induced metabolic dysfunction and demonstrated exercise-like physiological effects in a metabolically challenged model. Despite mechanistic differences from classical exercise-induced adaptations, the overall phenotype supports discussion of Cimicifuga racemosa extract Ze 450 as a plant-derived metabolic modulator with exercise-associated properties.

Background : High-intensity Interval Training (HIIT) is a time-efficient form of exercise and has gained popularity in recent years. However, at molecular level, the understanding about the effects of HIIT is not comprehensive, and even less is elucidated about HIIT of different training duration cycles, although different durations always lead to different post-training consequences. Method: In this study, by training SD rats using HIIT protocols lasting for different training duration cycles, we investigated the adaptive response of intramuscular triglyceride abundance and mitochondria enhancement after HIIT training (2, 4, 6, 8, and 10 weeks). We selected 72h after the last session of training as the time point of sacrifice. Results: The suppressed activation of the cAMP-PKA pathway indicates that skeletal muscle was in the recovery phase at this time point. Intramuscular triglyceride abundance was significantly elevated after 2, 4, and 10 weeks of HIIT. However, the lipid metabolism-related proteins inconsistently changed in a chaotic trend (see Table. 1). The expression levels of PGC1-α and COX IV decreased after 2 and 4 weeks of training and began to rise when the training duration reached 6 weeks. Interestingly, the variation tendency of PGC1-α and COX IV is very similar to that of CPT-1B. Conclusion: Given the fact that CPT-1B is responsible for the transfer of free fatty acids into the mitochondria to facilitate muscular lipid oxidation, there is a great possibility that: A) the IMTG accumulation observed within 0-4 weeks [defined as phase 1 here] of HIIT might be primarily attributed to damaged mitochondria oxidation capacity. B) when the training duration reached 6 weeks [defined as phase 2], mitochondria function and biogenesis began to be improved by training stimulus and might result in the disappearance of IMTG increase. We believe the phase 2 is rather similar to the condition of athletes` paradox, which should be a healthy adaptation induced by exercise training. Also, for HIIT Rat Modelling, intervention duration cycles longer than 4 weeks are recommended if similar HIIT frame of this study is used.

Preservation of skeletal muscle is an important consideration when evaluating weight-loss interventions, particularly during menopause, when adverse changes in body composition occur. We investigated the effects of Cimicifuga racemosa extract Ze 450 on skeletal muscle. Differentiated C2C12 myotubes were treated with Ze 450, dexamethasone (DEX), or their combination. Non-ovariectomized female Wistar rats were assigned to one of five groups: standard diet, high-fat diet (HF), HF plus voluntary running, HF plus Ze 450 (130 mg/kg/day), or HF plus Ze 450 and voluntary running. Muscle mass and fiber cross-sectional area (CSA) were assessed in the predominantly glycolytic gastrocnemius and oxidative soleus. Markers of mitochondrial content (COX IV and CS), lipid metabolism (ATGL, HSL, FAS, and SREBP-1c), glucose transport (GLUT4), and myogenic signaling (IGF-1) were analyzed. Ze 450 had limited effects on myotube diameter under basal conditions but significantly attenuated DEX-induced myotube atrophy. In vivo, Ze 450 reduced body weight gain and fat accumulation without reducing muscle mass or fiber CSA. Ze 450 differentially affected metabolic markers in the two muscle types, decreasing markers associated with mitochondrial content in the soleus while increasing mitochondrial markers in the gastrocnemius. Taken together, these findings suggest a potential role for Ze 450 in rebalancing skeletal muscle metabolism in a muscle-type-specific manner while preserving skeletal muscle during reductions in body weight gain and adiposity.