Zou Huawei, Hu Rui, Dong Xianwen, Shah Ali Mujtaba, Wang Zhisheng, Ma Jian, Peng Quanhui, Xue Bai, Wang Lizhi, Zhang Xiangfei, Zeng Shaoyu, Wang Xueying, Shi Junhua, Li Fengpeng
"Low Carbon Breeding Cattle and Safety Production" University Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 61130, China.
Department of Livestock Production, Shaheed Benazir Bhutto University of Veterinary and Animal Sciences, Sakrand 67210, Pakistan.
Animals (Basel). 2020 Jan 15;10(1):136. doi: 10.3390/ani10010136.
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.
脂质是饥饿动物的主要能量来源。β-羟基丁酸（BHBA）是脂质分解产生的主要酮体。在中国仓鼠卵巢（CHO）细胞实验中发现，BHBA不仅可以作为能量物质，还可以作为GPR109A的配体来调节脂质代谢。然而，BHBA是否能调节牦牛的脂质代谢及其有效浓度和信号通路尚不清楚。本研究探讨了饥饿和BHBA对牦牛脂质代谢的影响及其机制。选取18头九龙雄性牦牛，随机分为三组：正常饲养组（NG）、饥饿组（SG）和饥饿+BHBA输注组（SBG）。NG组牦牛在试验期间自由采食，SG组和SBG组牦牛禁食；实验第7至9天，NG组和SG组持续输注0.9%生理盐水，SBG组输注1.7 mmol/L BHBA溶液。在实验的第0、1、3、5、7和9天采集血样。本研究中所有牦牛的皮下脂肪组织在输注后取自活体。检测血清葡萄糖、脂质代谢产物、激素浓度以及皮下脂肪组织中脂质代谢和信号通路关键因子的mRNA和蛋白表达。结果表明，与NG组相比，饥饿显著降低了SG组牦牛的体重，显著提高了血清中BHBA的浓度以及皮下脂肪组织中PKA和CREB1的mRNA表达，而MEK、PKC、ERK1/2的mRNA表达、脂肪细胞面积和饱和脂肪酸比例降低。然而，通过输注进一步提高BHBA浓度促进了SBG组皮下脂肪组织中GPR109A受体的mRNA表达，抑制了AC和PKA的mRNA表达，降低了CREB1的磷酸化蛋白丰度，并显著增加了脂肪细胞的直径和面积。这些结果表明，饥饿导致牦牛脂质分解代谢增强。BHBA浓度的增加可提高皮下脂肪组织中GPR109A受体的mRNA表达，抑制cAMP/PKA/CREB信号通路和脂质分解。
