Lipid Catabolism in Starved Yak Is Inhibited by Intravenous Infusion of β-Hydroxybutyrate
Lipid Catabolism in Starved Yak Is Inhibited by Intravenous Infusion of β-Hydroxybutyrate
复制标题
静脉输注β-羟基丁酸可抑制饥饿牦牛的脂质分解代谢
DOI：
10.3390/ani10010136
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发表时间：
2020-01
期刊：
影响因子：
3
通讯作者：
Fengpeng Li
中科院分区：
文献类型：
--
作者：
Huawei Zou;Rui Hu;Xianwen Dong;Ali Mujtaba Shah;Zhisheng Wang;Jian Ma;Quanhui Peng;Bai Xue;Lizhi Wang;Xiangfei Zhang;Shaoyu Zeng;Xueying Wang;Junhua Shi;Fengpeng Li
牦牛是青藏高原的优势半驯养家畜，由于高原环境恶劣，在寒冷季节会遭受严重的饥饿和体重下降。脂肪是饥饿动物的重要能量来源。β-羟基丁酸酯（β-hydroxybutyrate，BHBA）是脂肪分解产生的初级酮体，不仅作为能量物质为动物提供能量，而且作为信号分子调节脂肪代谢。然而，饥饿和BHBA对反刍动物脂质代谢的影响及其机制尚不清楚。本文研究了饥饿和静脉输注BHBA溶液对牦牛生长、血清生化、激素、皮下脂肪细胞形态、脂肪酸组成、脂代谢相关酶活性和信号通路的影响。结果表明，饥饿促进脂肪分解，BHBA处理上调皮下脂肪组织GPR 109 A受体mRNA表达，抑制环磷酸腺苷（cAMP）/蛋白激酶A（PKA）/cAMP反应元件结合蛋白（CREB）信号通路，抑制脂肪分解。本研究对丰富牦牛的营养调控理论，提高牦牛的生长潜力具有重要意义。摘要脂肪是饥饿动物的主要能量来源。β-羟基丁酸酯（BHBA）是脂肪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GPR 109 A的配体调节脂质代谢。但BHBA是否能调节牦牛的脂质代谢，其有效浓度和信号通路尚不清楚。本研究探讨了饥饿和BHBA对牦牛脂肪代谢的影响及其机理。选取18头雄性九龙牦牛，随机分为3组：正常饲养组（NG）、饥饿组（SG）和饥饿加BHBA组（SBG）。试验期间NG组自由采食，SG组和SBG组禁食，试验第7 ~ 9天NG组和SG组连续输注0.9%生理盐水，SBG组输注1.7 mmol/L BHBA溶液。分别于实验第0、1、3、5、7、9天采血。本试验所用牦牛皮下脂肪组织均取自输注后的活体。测定血糖、脂代谢产物、激素浓度以及皮下脂肪组织脂代谢关键因子和信号通路的mRNA和蛋白表达。结果表明，与NG组相比，饥饿组牦牛体重显著降低，血清中BHBA浓度显著升高，皮下脂肪组织中PKA和CREB 1 mRNA表达显著增加，而MEK、PKC、ERK 1/2 mRNA表达、脂肪细胞面积和饱和脂肪酸比例显著降低。进一步增加BHBA浓度可促进皮下脂肪组织GPR 109 A受体mRNA表达，抑制AC和PKA mRNA表达，降低CREB 1磷酸化蛋白丰度，显著增加脂肪细胞直径和面积。这些结果表明，饥饿导致牦牛体内脂质代谢增强。随着BHBA浓度的增加，皮下脂肪组织GPR 109 A受体mRNA表达增加，cAMP/PKA/CREB信号通路受到抑制，脂质分解受到抑制。
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.
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影响因子：
3.7
作者：
Hu R;Wang Z;Peng Q;Zou H;Wang H;Yu X;Jing X;Wang Y;Cao B;Bao S;Zhang W;Zhao S;Ji H;Kong X;Niu Q
通讯作者：
Niu Q
影响因子：
10.5
作者：
Kim, JB;Spiegelman, BM
通讯作者：
Spiegelman, BM
影响因子：
3.3
作者：
B. Xue;X. Zhao;Y. Zhang
通讯作者：
B. Xue;X. Zhao;Y. Zhang
DOI：
--
发表时间：
--
期刊：
--
影响因子：
--
作者：
K. Livak;Thomas D. Schmittgen
通讯作者：
K. Livak;Thomas D. Schmittgen
DOI：
10.1093/jn/110.12.2490
发表时间：
1980-12
期刊：
The Journal of nutrition
影响因子：
--
作者：
S. Yaffe;Armand J. Gold;Joseph Sampugna
通讯作者：
S. Yaffe;Armand J. Gold;Joseph Sampugna