Author(s): MIYAZAKI, T., HONDA, A., Institution: TOKYO MEDICAL UNIVERSITY, Country: JAPAN, Abstract-ID: 782

INTRODUCTION:
Branched-chain amino acids (BCAAs) are catabolized for energy substrates in the skeletal muscles to fulfill high energy demands, instead of decreased glucose supply, during endurance exercise and in metabolic diseases. We have presented in ECSS that a small molecule 3-hydroxyisobutyric acid (3HIB) was produced as an intermediate of valine in the mitochondrial catabolic pathway, and some of which was released from the skeletal muscles to blood circulation, dependently on the amount of endurance exercises in humans and animals. We hypothesized that 3HIB has any physiological role in energy metabolism in response to decreased glucose supply. The present study evaluated the effect of 3HIB on blood glucose concentration in rats.
METHODS:
Male Wister rats (8 weeks of age) were intraperitoneally injected with PBS or 6% 3HIB solution as 60 mg/kg BW (N=3/groups), and glucose and 3HIB levels were measured in blood samples collected through a silicone catheter inserted into the jugular vein every 5 min for 60 min. In addition, blood and liver were collected from the rats at 0, 15, and 60 min (N=7/groups) after the i.p. injections of PBS or 3HIB. Furthermore, an alpha blocker prazosin was also injected as 5 mg/kg BW i.p. before the 3HIB injection (N=7/groups). Energy metabolites, mRNA expression, and glucose-regulation hormones were measured in the samples.
RESULTS:
In over time observation, blood glucose level was significantly increased after 5 min of the 3HIB injection accompanied with the significant increase of 3HIB, and then, glucose level was decreased but kept at higher levels until 60 min. After 15 min when significantly higher levels of glucose and 3HIB were kept, serum adrenaline and corticosterone concentrations were significantly increased and decreased, respectively, while noradrenaline, glucagon, insulin, and thyroid hormones were unchanged. The effects of 3HIB injection on blood glucose and hormones were canceled by prazosin. In the liver, glucose 6-phosphatase mRNA expression and fumarate and malate concentrations were significantly increased after 15 min of 3HIB injection.
CONCLUSION:
The increased 3HIB concentration in serum significantly enhanced blood glucose levels with the increased adrenaline concentration in serum and gluconeogenesis-related genes and metabolites. A BCAA catabolic metabolite 3HIB derived from the skeletal muscles in endurance exercises might have a feedback effect to improve the metabolic shift by enhancing blood glucose levels through the sympathetic nervous system.