====== β-Hydroxybutyrate ======

β-[[Hydroxybutyrate]] (β-HB) is a chemical compound that belongs to the group of [[ketone]] bodies. 
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It serves as one of the primary alternative [[energy]] sources to glycogen during periods of low [[carbohydrate]] availability, such as prolonged fasting or a [[ketogenic diet]]. β-HB is produced in the [[liver]] through the [[oxidation]] of [[fatty acid]]s and, along with other ketone bodies like [[acetoacetate]] and [[acetone]], is transported to various organs, particularly the brain and muscles, where it can be converted into energy.

This compound is significant because:

- **Energy source**: It provides an efficient fuel for the brain and body during carbohydrate scarcity.

- **Brain function**: β-HB can cross the blood-brain barrier, offering an alternative energy source for neurons.

- **Metabolic benefits**: It may support improved metabolic health by promoting fat metabolism and influencing pathways related to cellular energy.
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The [[ketogenic diet]] (KD) has demonstrated efficacy in ameliorating [[inflammation]] in [[rat]]s with [[osteoarthritis]] (OA). However, the long-term [[safety]] of the KD and the underlying mechanism by which it delays OA remain unclear. 
Cai et al. found that while long-term KD could ameliorate OA, it induced severe hepatic [[steatosis]] in [[mice]]. Consequently, they developed two versions of ketogenic-based diets: KD supplemented with [[vitamin D]] and intermittent KD. Both KD supplemented with vitamin D and intermittent KD effectively alleviated OA by significantly reducing the levels of inflammatory [[cytokine]]s, cartilage loss, sensory nerve sprouting, and knee [[hyperalgesia]] without inducing hepatic steatosis. Furthermore, β-hydroxybutyrate (β-HB), a convenient energy carrier produced by [[adipocyte]]s, could ameliorate OA without causing liver lesions. Mechanistically, β-HB enhanced [[chondrocyte]] [[autophagy]] and reduced [[apoptosis]] through the activation of the [[Erb-B2]] receptor tyrosine kinase 3 ([[ERBB3]]) signaling pathway; a pathway which was down-regulated in the articular chondrocytes from both OA patients and mice. Collectively, the findings highlighted the potential therapeutic value of β-HB and KD supplemented with [[vitamin D]] and intermittent KD approaches for managing OA
((Cai Z, Zhang Z, Leng J, Xie M, Zhang K, Zhang J, Zhang H, Hu H, Deng Y, Bai X, Song Q, Lai P. β-hydroxybutyrate ameliorates [[osteoarthritis]] through activation of the ERBB3 signaling pathway in mice. J Bone Miner Res. 2024 Nov 5:zjae176. doi: 10.1093/jbmr/zjae176. Epub ahead of print. PMID: 39498503.)).