Review ArticleAltered cholesterol and fatty acid metabolism in Huntington disease
Section snippets
Lipid metabolism in Huntington disease
Cholesterol is crucial for myelin membrane growth, and mice that cannot properly synthesize cholesterol manifest tremor and ataxia.5 In addition to its central nervous system-specific role, cholesterol is an essential component of all cell membranes, acting as a structural component, organizing signal transduction in the lipid rafts of cell membranes, and playing a role in synaptogenesis and in neurotransmitter release within synapses.6 Cholesterol also plays a vital role as a cofactor for
Insulin resistance in Huntington disease
Insulin resistance is a pathophysiologic state associated with obesity and aging and characterized by hyperglycemia and dysfunctional lipid metabolism.17 It is associated with an increased risk of cardiovascular disease and diabetes mellitus as well as certain neoplasms including those of the breast and colon. The lipid disorder tends to consist of high triglycerides and small, dense low-density lipoprotein, with an accompanying high number of atherogenic (apoB) particles. The primary concerns
The role of omega-3 fatty acids in central nervous system health
The state of insulin resistance is characterized by hyperglycemia, abnormal lipoprotein metabolism, and elevated levels of circulating free fatty acids.17 The intake and concentrations of long-chain polyunsaturated fatty acids, including the fish-derived omega-3 fatty acids docosahexaenoic (DHA) and eicosapentaenoic acids (EPA), are negatively correlated with insulin resistance and its manifestations, whereas intake and concentrations of saturated fatty acids are positively correlated.23 A
Implications of disturbed lipid metabolism in Huntington disease
EPA's potential neuroprotective effects and the disrupted fatty acid metabolism in Huntington disease raise the question of whether targeting lipid metabolism may be useful therapies for individuals with Huntington disease. The fact that EPA has beneficial effects on triglycerides is not novel. However, because Huntington disease is characterized by insulin resistance and hypertriglyceridemia is one characteristic of insulin resistance, a beneficial effect of EPA on triglycerides in Huntington
Future directions for the treatment of Huntington disease
Because Huntington disease is characterized by a pattern of impaired insulin secretion and insulin resistance in the setting of hypercatabolism and weight loss, the presentation of insulin resistance and diabetes appears to be very different than that for the majority of individuals with type 2 diabetes mellitus and the metabolic syndrome. Reductions in insulin secretion suggest a pathophysiology similar to type 1 diabetes mellitus, but this form of diabetes is immunologic, not degenerative, in
Financial disclosures
The project was supported by grant number KL2 RR 024136 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and the NIH Roadmap for Medical Research, and RO1 HG 02449 from the National Human Genome Research Institute, and its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Information on NCRR is available at http://www.ncrr.nih.gov/. Information on Re-engineering
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