Lipid Catabolism in Starved Yak Is Inhibited by Intravenous Infusion of β-Hydroxybutyrate

SIMPLE SUMMARY: Yak, which is the predominant and semi-domesticated livestock on the Qinghai-Tibet Plateau, suffers severe starvation and body weight reduction in the cold season because of the harsh highland environment. Lipids are important energy sources to starvation animals. β-hydroxybutyrate (BHBA) that is derived from lipid decomposition as the primary ketone body is with the function not only to provide energy for animals as energy materials, but also regulate lipid metabolism as signaling molecular. However, the effects of starvation and BHBA on lipid metabolism and its mechanism are still unclear for ruminant animals. Herein, we investigated the effects of starvation and intravenous infusion of BHBA solution on Yak growth, serum biochemistry, hormones, subcutaneous adipocyte morphology, fatty acid composition, activity of enzymes related to lipid metabolism, and signal pathway. The results showed that starvation promoted lipid catabolism and BHBA infusion up-regulated the mRNA expression of receptor GPR109A in subcutaneous adipose tissue, inhibited the Cyclic adenosine monophosphate(cAMP)/Protein kinase A (PKA)/cAMP-responsive element binding protein (CREB) signaling pathway, and inhibited lipolysis. Our study was beneficial for enriching the nutrition regulation theory of yaks and improving their growth potential. ABSTRACT: Lipid is the chief energy source for starved animals. β-hydroxybutyrate (BHBA) is the main ketone body produced by lipid decomposition. In Chinese hamster ovary (CHO) cell experiment, it was found that BHBA could be used not only as an energy substance, but also as a ligand of GPR109A for regulating lipid metabolism. However, whether BHBA can regulate lipid metabolism of yaks, and its effective concentration and signal pathway are not clear. This study investigated the effects and mechanism of starvation and BHBA on the lipid metabolism of yak. Eighteen male Jiulong yaks were selected and then randomly divided into three groups: normal feeding group (NG), starvation group (SG), and starvation with BHBA infusion group (SBG). The yaks in the NG group were freely fed during the trial, while the yaks in the SG and SBG groups fasted; from 7th to 9th days of the experiment, the NG and SG were infused continuous with 0.9% normal saline and SBG was infused 1.7 mmol/L BHBA solution respectively. The blood samples were collected on the 0th, 1st, 3rd, 5th, 7th, and 9th day of experiment. The subcutaneous adipose tissue of all the yaks in this study were taken from live bodies after infusion. Serum glucose, lipid metabolites, hormone concentrations, and mRNA and protein expressions of key factors of lipid metabolism and signaling pathway in subcutaneous adipose tissue were measured. The results showed that, as compared with NG, starvation significantly reduced the body weight of yak in SG, and significantly increased the concentration of BHBA in serum and the mRNA expression of PKA and CREB1 in subcutaneous adipose tissue, while the mRNA expression of MEK, PKC, ERK1/2, the area of adipocytes, and the proportion of saturated fatty acid were decreased. Whereas, further increase of BHBA concentration through infusion promoted the mRNA expression of GPR109A receptor in the subcutaneous adipose tissue of SBG, inhibited the mRNA expression of AC and PKA, and decreased the phosphorylation protein abundance of CREB1, and significantly increased the diameter and area of adipocytes. These findings suggest that starvation led to enhanced lipid catabolism in yaks. An increasing BHBA concentration could increase the mRNA expression of GPR109A receptor in subcutaneous adipose tissue and inhibit the cAMP/PKA/CREB signaling pathway and lipid decomposition.