Diet-induced metabolic disturbances as modulators of brain homeostasis - PubMed (original) (raw)

Review

Diet-induced metabolic disturbances as modulators of brain homeostasis

Le Zhang et al. Biochim Biophys Acta. 2009 May.

Abstract

A number of metabolic disturbances occur in response to the consumption of a high fat western diet. Such metabolic disturbances can include the progressive development of hyperglycemia, hyperinsulemia, obesity, metabolic syndrome, and diabetes. Cumulatively, diet-induced disturbances in metabolism are known to promote increased morbidity and negatively impact life expectancy through a variety of mechanisms. While the impact of metabolic disturbances on the hepatic, endocrine, and cardiovascular systems is well established there remains a noticeable void in understanding the basis by which the central nervous system (CNS) becomes altered in response to diet-induced metabolic dysfunction. In particular, it remains to be fully elucidated which established features of diet-induced pathogenesis (observed in non-CNS tissues) are recapitulated in the brain, and identification as to whether the observed changes in the brain are a direct or indirect effect of peripheral metabolic disturbances. This review will focus on each of these key issues and identify some critical experimental questions which remain to be elucidated experimentally, as well as provide an outline of our current understanding for how diet-induced alterations in metabolism may impact the brain during aging and age-related diseases of the nervous system.

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Figures

Figure 1

Figure 1. Progression from euglycemic state to diabetes

In contrast to the a healthy euglycemic state, the consumption of a western diet is sufficient to increase the dysfunction of a number of aspects of metabolism. The temporal profile by which many on these metabolic disturbances occur is provided to allow for identification of early and late events in the progression to diabetes. HDL: high density lipoprotein; BMI: body mass index.

Figure 2

Figure 2. Diet-induced increases in brain dysfunction and brain pathology

Consumption of a western diet is sufficient to promote metabolic dysfunction that can then lead to the development of brain pathology and cognitive disturbances. Aging likely promotes the ability of a western diet to promote metabolic dysfunction, and deleterious effects on the brain, while several clinically relevant interventions (western diet cessation, antioxidants, anti-inflammatory, anti-diabetics) likely ameliorate the effects of a western diet on metabolism and the brain.

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