Dissertation > Agricultural Sciences > Livestock, animal medicine,hunting,silkworm,bee > Livestock > Cow

The Signaling Mechanism of Acetic Acid, Non-esterified Fatty Acids, Growth Hormone and Prolactin on the Regulation of Lipid Metabolism in the Hepatocytes of Dairy Cows

Author LiXinWei
Tutor WangZhe
School Jilin University
Course Clinical Veterinary Medicine
Keywords Acetic acid Non-esterified fatty acids Growth hormone Prolactin Lipidmetabolism of bovine hepatocyte dairy cows
CLC S823
Type PhD thesis
Year 2013
Downloads 143
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Milk fat is an important nutrient composition in milk. The synthesis of milk fat isregulated by neuroendocrine hormone, cytokines, and nutrition metabolic signals suchas milk fat precursors. Liver is the main organ for regulating and assigning milk fatprecursors. Liver transports the nutrition to breast for milk fat synthesis under theregulation of neuroendocrine hormone, cytokines, and nutrition metabolic signals indairy cows of lactation period. Growth hormone (GH) and prolactin (PRL) is the mostimportant hormone for the regulation of milk fat synthesis in dairy cows. Furthermore,several studies demonstrated that the acetic acid and non-esterified fatty acids(NEFAs) act as signaling molecules to regulate the expression of lipid metabolismgenes in the liver. Therefore, the objective of the present experiment was toinvestigate the signaling mechanism of GH, PRL, acetic acid and NEFAs on thehepatic lipid metabolism in the bovine hepatocytes cultured in vitro, which shouldprovide valuable information to improve the content of milk fat in dairy cows.Acetic acid regulates the lipid metabolism through AMP-activated protein kinase(AMPK) signaling pathway. Acetic acid is metabolized to acetyl-CoA in hepatocytes withthe consumption of ATP. An elevated AMP/ATP ratio increases the phosphorylation andactivity of AMPKα. Activated AMPKα increases the expression and transcriptional activityof peroxisome proliferator-activated receptor α (PPARα), thereby increasing the expression oflipolytic genes. Furthermore, activated AMPKα inhibits the expression and transcriptionalactivity of sterol regulatory element-binding protein1c (SREBP-1c) and carbohydrateresponsive element-binding protein (ChREBP), thereby reducing the expression of lipogenicgenes. In addition, activated AMPKα directly phosphorylate acetyl-CoA carboxylase1(ACC1) and inhibit its activity, and indirectly increase carnitine palmitoyltransferase1(CPT-1) activity. Consequently, acetic acid activates AMPKα signaling pathway, whichincreases lipolysis and decreases lipid synthesis in bovine hepatocytes, thereby reducing hepatic fat accumulation in dairy cows.NEFAs regulate the lipid metabolism through AMPK signaling pathway. NEFAsactivate AMPKα through increasing the expression of liver kinase B1. Activated AMPKαincreases the expression and transcriptional activity of PPARα. NEFAs also activate PPARαindependent of AMPKα in a ligand manner. Activated PPARα increases the expression oflipolytic genes. Activated AMPKα inhibits the expression and transcriptional activity ofSREBP-1c and ChREBP, thereby reducing the expression of the lipogenic genes. In addition,activated AMPKα directly phosphorylate ACC1and inhibit its activity, and indirectly increaseCPT1activity. Consequently, NEFAs increase lipid oxidization and inhibit lipid synthesis inbovine hepatocytes to produce more ATP.GH activates Janus kinase2-transcription factor signal transducer and activatorof transcription5(JAK2-STAT5) signaling pathway to promote the synthesis andsecretion of insulin-like growth factor (IGF-1). IGF-1activates phosphatidyl inositol3-kinase-protein kinase B (PI3K-Akt) signaling pathway, which increases theexpression and transcriptional activity of SREBP-1c, thereby increasing lipid synthsisand transportion in bovine hepatocytes. The synthesized TG is used for the syntheis ofmilk fat. Furthermore, GH activates JAK2-STAT5signaling pathway, which inhibitsthe expression and transcriptional activity of PPARα, thereby decreasing lipidoxidation in bovine hepatocytes.PRL activates PI3K-Akt signaling pathway, which increases the expression andtranscriptional activity of SREBP-1c. Activated SREBP-1c increases the expression of lipidsynthsis and transportion genes, which promotes the synthesis and transportion of TG inbovine hepatocytes, thereby providing more precursors for the milk fat synthsis.In summary, acetic acid and NEFAs increase lipid oxidation and decrease lipidsynthesis in bovine hepatocytes, which reduces fat accumation. GH and PRL increaselipid synthsis and transportion in bovine hepatocytes, thereby providing more milk fatprecursors for milk fat synthesis.

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