BACKGROUND:In response to physiologic stressors, skeletal muscle has the potential to elicit wide variety of adaptive responses, such as biogenesis of mitochondria and clearance of damaged mitochondria to promote healthy muscle. The polyphenol curcumin, derived from the rhizome Curcuma longa L., is a natural antioxidant that exhibits various pharmacological activities and therapeutic properties. However, the effect of curcumin on the regulation of mitochondrial biogenesis in skeletal muscle remains unknown. The present study aimed to examine the effects of combination of endurance training (eTR) and curcumin treatment on the expression of AMPK, SIRT1, PGC-1α, and OXPHOS subunits, mitochondrial DNA copy number, and CS activity in rat skeletal muscle. Furthermore, the present study also examined the effect of exercise and curcumin treatment on the levels of cAMP and downstream targets of PKA including phosphorylated CREB and LKB-1.

METHODS:Ten-week-old male Wistar rats were randomly divided into non-eTR and eTR groups. Low doses (50 mg/kg-BW/day) or high doses (100 mg/kg-BW/day) of curcumin dissolved in dimethyl sulfoxide (DMSO) were injected intraperitoneally in all animals for 28 days to investigate the effect of curcumin alone and the combined effect of curcumin with eTR. Western blotting (WB) and immunoprecipitation (IP) were performed to detect the presence of proteins.

RESULTS:Our results demonstrated that combination of curcumin treatment and eTR increased the expression of COX-IV, OXPHOS subunits, mitochondrial DNA copy number and CS activity in the gastrocnemius (Gas) and soleus (Sol) muscles. In addition, this combination increased AMPK phosphorylation, NAD(+)/NADH ratio, SIRT1 expression, and PGC-1α deacetylation. Furthermore, curcumin treatment as well as exercise also increased levels of cAMP and downstream target of PKA including phosphorylation CREB and LKB-1 which are involved in the regulation of mitochondrial biogenesis.

CONCLUSION:Taken together, these results suggest that the combination of curcumin treatment and eTR has the potential to accelerate mitochondrial biogenesis in skeletal muscle by increasing cAMP levels.

Obesity increases inflammation, both peripherally and centrally, and exercise can ameliorate some of the negative health outcomes associated with obesity. Within the brain, the effect of obesity on inflammation has been well characterized in the hypothalamus and hippocampus, but has been relatively understudied in other brain regions. The current study was designed to address two primary questions; (1) whether western diet (high fat/high sucrose) consumption would increase markers of inflammation in the prefrontal cortex and (2) whether concurrent voluntary wheel running would ameliorate any inflammation. Adult male mice were exposed to a western diet or a control diet for 8 weeks. Concurrently, half the animals were given running wheels in their home cages, while half did not have access to wheels. At the conclusion of the study, prefrontal cortex was removed and expression of 18 proinflammatory genes was assayed. Expression of a number of proinflammatory molecules was upregulated by consumption of the western diet. For two chemokines, chemokine (C-C motif) ligand 2 (CCL2) and C-X-C motif chemokine 10(CXCL10), voluntary exercise blocked the increase in the expression of these genes. Cluster analysis confirmed that the majority of the tested genes were upregulated by western diet, and identified another small cluster of genes that were downregulated by either diet or exercise. These data identify a proinflammatory phenotype within the prefrontal cortex of mice fed a western diet, and indicate that chemokine induction can be blocked by voluntary exercise.