Ketone strong: emerging evidence for a therapeutic role of ketone bodies in neurological and neurodegenerative diseases.

摘要: Chronic inflammatory disease is emerging as a major health crisis in the US. Many Americans are suffering from plethora of chronic diseases including obesity, type 2 diabetes, cardiovascular disease, and cancer. acute inflammation also linked to several brain that include epilepsy, Alzheimer’s Parkinson’s traumatic injury (TBI), glioma. Diet lifestyle issues contribute pathology those these other diseases. Hence, management one means reducing burden (1, 2). Humans mammals have evolved function for considerable periods without food (2, 3). While glucose primary fuel under normal fed states, water-soluble ketone bodies, β-hydroxybutyrate (β-OHB) acetoacetate, can compensate metabolic organs conditions prolonged fasting (4). The liver makes bodies naturally fatty acids released largely stored body fat (triglycerides). Changes key hormones, insulin glucagon, regulatory genes orchestrate physiological transition between glucose-dependent state lipid-dependent fasted state. Although ketoacidosis was originally ketosis generally improved health. difference blood β-OHB levels distinguishes (>20 mM) (1–8 mM). Acetone nonenzymatic degradation product acetoacetate be easily detected breath individuals with diabetic (mostly 1), or who conduct water-only therapeutic fasting. Calorie restriction (CR) has long been recognized improve general health, manage broad range diseases, delay aging 5). produce oxidative stress ultimately damages tissue biomolecules. Hyperglycemia 6). Oxidative accelerates entropy, thermodynamic basis process (7). CR reduces stress, which entropy. effects associated reduction elevation within ranges. Veech (8) showed metabolism reduce by increasing redox span mitochondrial coenzyme Q couple, amount semiquinone thus oxygen radical production cells normally functioning mitochondria. It difficult determine, however, if benefits related glucose, unique arising combination effects. Figure 1 illustrates relationship disease. Fig. 1. Relationship plasma management. values ranges mice benefit epilepsy ... Although periodic (9), will eventually lead pathological starvation (10), while nutritional imbalances unless composition restricted diet carefully monitored. Nevertheless, evidence indicates dietary therapies, lower elevate safe children adults, effective variety neurological neurodegenerative (11). We recently predictor weight C57/BL6 mouse strain (12). lowers elevating ketones regardless macronutrient consumed diet. Most popular loss diets form CR. A ketogenic (KD) low carbohydrate high-fat designed seizures (13). KD mimics fasting, known since time Hippocrates seizure susceptibility. An energy thought KDs. As CR, it remains unclear anti-epileptic anti-convulsant due reduced elevated some Circulating become higher when KDs administered amounts than unrestricted (12, 14). described how KDs, drugs hyperbaric therapy, could help cancer (15). A similar strategy used managing diseases. The therapy must care, would case any medical therapy. should excessive consumption weight, potentially hyperlipidemia insensitivity thereby 14, 16). high concentration usually prevent excess gain. powerful Recent against arise through its action an endogenous histone deacetylase inhibitor (17). These findings reveal global shift regulate gene expression epigenetic mechanisms. Synthetic esters appear replicate features but further studies necessary establish connections (18). molecular mechanisms underlie now active investigation. This Thematic Review Series highlight current research potential KDs. The first review series Hashim Vanitallie (19) provides historical perspective ketones, management, segue reviews. (20) highlights bioenergetics this role transcriptional regulators. Gano, Patel, Rho (21) linkage neuroprotective bodies. Prins Matsumoto (22) TBI. TBI concern National Football League veterans Iraq Afghanistan wars. alternative complimentary malignant (23). Woolf Scheck (24) information supporting possibility. articles stimulate into shifts act nervous system. Journal Lipid Research, traditional focus on science lipids ideal forum disseminating field.