Alpha-Ketoglutarate as a Dietary Supplement to Enhance Health and Exercise Performance

Skeletal muscle is the largest metabolic organ in the body. It is made up of muscle fibers, blood vessels, nerves and connective tissue. In skeletal muscle, blood vessels are responsible for the transport of oxygen, nutrients, and metabolic wastes, and are of critical importance in muscle development, hypertrophy, and metabolic regulation.

Based on their metabolic properties, skeletal muscle fibers can be broadly divided into ‘slow-twitch’ (type I) and ‘fast-twitch’ (type II), with type I slow-switch fibers being slowly oxidized. Type II fast-twitch fibers can be further classified into three major subtypes based on differential expression of myosin heavy chain (MYH). muscle fibers), it is generally accepted that humans do not have type IIB fibers.

In skeletal muscle, slow-oxidizing type I fibers have good blood perfusion and high capillary density. It is directly related to the proportion of muscle fibers.

During contraction, skeletal muscle releases various metabolites such as pyruvate (PA) and lactate (LA), end products of glycolysis, and α-ketoglutarate, an intermediate metabolite of the tricarboxylic acid (TCA) cycle. Emit (AKG). and succinic acid (SUC). LA and SUC have been shown to regulate vasodilation that allows tissues to receive abundant oxygen and nutrients, but it is unclear whether AKG serves a similar function.

AKG is an important intermediate metabolite of the TCA cycle that is released during exercise. Previous studies have shown that AKG has biological functions such as regulating energy metabolism, promoting bone formation, enhancing immunity, and extending animal lifespan. Oxoglutarate receptor 1 (OXGR1) is the endogenous receptor for AKG, expressed primarily in tissues of the nervous system, adrenal glands, and reproductive system, whereas skeletal muscle has relatively low expression of OXGR1. A previous study published by Professors Gang Shuang and Qingyan Jiang of South China Agricultural University demonstrated that adding AKG to drinking water reduced fat deposition and increased skeletal muscle mass. Consistently, skeletal muscle underwent profound atrophy in mice with a global knockout of OXGR1. So far, the expression and function of OXGR1 in skeletal muscle are unknown.

On September 29, 2022, the same group published a study in Life Metabolism titled, “AKG/OXGR1 promotes skeletal muscle blood flow and metabolism by relaxing vascular smooth muscle,” demonstrating that AKG/OXGR1 regulates vascular It has been shown that relaxation of smooth muscle regulates skeletal muscle metabolism. This study reports for the first time that His OXGR1 in skeletal muscle is primarily distributed in vascular smooth muscle (slow-oxidizing muscle) in the soleus muscle. Using OXGR1 systemic knockout and vascular smooth muscle-specific knockout HIS mouse models, they found that HIS OXGR1 is essential for skeletal muscle type switching and metabolism. Further studies revealed that the AKG/OXGR1 signaling pathway can relax vascular smooth muscle by lowering the intracellular pH of the vascular smooth muscle. Furthermore, supplemental AKG supplementation not only helps promote muscle development, but also promotes the conversion and metabolism of skeletal muscle to oxidative muscle fibers, ultimately leading to improved athletic performance or meat quality in livestock. (Figure 1).

This study provides new insights into the nutritional regulation of AKG as a nutrient to improve health and athletic performance in specific populations (sedentary people and athletes), and meat yield and quality in livestock.