Abstract
Background: In the pathogenesis of central nervous system disorders (e.g., neurodegenerative), an important role is attributed to an unhealthy lifestyle affecting brain energy metabolism. Physical activity in the prevention and treatment of lifestyle-related diseases is getting increasing attention. Methods: We performed a series of assessments in adult female Long Evans rats subjected to 6 weeks of Western diet feeding and wheel-running training. A control group of lean rats was fed with a standard diet. In all experimental groups, we measured physiological parameters (animal weights, body composition, serum metabolic parameters). We assessed the impact of simultaneous exposure to a Western diet and wheel-running on the cerebrocortical protein expression (global proteomic profiling), and in the second part of the experiment, we measured the cortical levels of protein related to brain metabolism (Western blot). Results: Western diet led to an obese phenotype and induced changes in the serum metabolic parameters. Wheel-running did not reduce animal weights or fat mass but significantly decreased serum glucose level. The global proteome analysis revealed that the altered proteins were functionally annotated as they were involved mostly in metabolic pathways. Western blot analysis showed the downregulation of the mitochondrial protein—Acyl-CoA dehydrogenase family member 9, hexokinase 1 (HK1)—enzyme involved in principal glucose metabolism pathways and monocarboxylate transporter 2 (MCT2). Wheel-running reversed this decline in the cortical levels of HK1 and MCT2. Conclusion: The cerebrocortical proteome is affected by a combination of physical activity and Western diet in female rats. An analysis of the cortical proteins involved in brain energy metabolism provides a valuable basis for the deeper investigation of changes in the brain structure and function induced by simultaneous exposure to a Western diet and physical activity.
Highlights
The Western diet pattern characterized by a high daily intake of saturated fats and refined carbohydrates often leads to overweight and obesity, which increase the risk of several debilitating and deadly diseases, including diabetes, heart disease, and some cancers [1]
Western diet-induced adverse effects in the brain seem to be related to disturbances of brain energy metabolism, especially to the principal glucose metabolic pathways
We reported an almost 2-fold increase in cortical levels of GLUT3 (p = 0.04), a major neuronal glucose transporter, in animals fed with a WD and exercised in wheels (WD/EX group), as compared to the WD group (ANOVA p = 0.028, F(2, 12) = 4.872; Figure 7D)
Summary
The Western diet pattern characterized by a high daily intake of saturated fats and refined carbohydrates often leads to overweight and obesity, which increase the risk of several debilitating and deadly diseases, including diabetes, heart disease, and some cancers [1]. Western diet-induced adverse effects in the brain seem to be related to disturbances of brain energy metabolism, especially to the principal glucose metabolic pathways. A Western diet may induce changes in the levels of other compounds important for brain energy homeostasis [7]. We assessed the impact of simultaneous exposure to a Western diet and wheel-running on the cerebrocortical protein expression (global proteomic profiling), and in the second part of the experiment, we measured the cortical levels of protein related to brain metabolism (Western blot). An analysis of the cortical proteins involved in brain energy metabolism provides a valuable basis for the deeper investigation of changes in the brain structure and function induced by simultaneous exposure to a Western diet and physical activity
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