Research Progress on the Mechanism of Milk Fat Synthesis in Cows and the Effect of Conjugated Linoleic Acid on Milk Fat Metabolism and Its Underlying Mechanism: A Review

Simple Summary Although fat does not constitute the largest proportion of cow milk composition, the energy consumed in milk fat production is the highest among all milk components. Milk fat can improve the flavor of milk, and it is an indicator of the nutritional value of milk; therefore, exploring the synthesis of milk fat in dairy cows has become a hot topic. The classic mechanism of milk fat biosynthesis involves the de novo synthesis of fatty acids (fatty acid synthase, acetyl-CoA carboxylase, etc.-abbreviated as FASN, ACACA, etc.); the uptake, transport, and activation of long-chain fatty acids (lipoprotein lipase, long-chain acyl-CoA synthetase, etc.-abbreviated as LPL, ACSL, etc.); the synthesis of triglycerides (1-acylglycerol-3-phosphate O-acyltransferase 6, Diacylglycerol acyltransferase, etc.-abbreviated as AGPAT6, DGAT, etc.); signaling pathways; and transcription factors (mechanistic target of rapamycin, sterol regulatory element-binding protein, peroxisome proliferator-activated receptor gamma, and adenosine monophosphate-activated protein kinase-abbreviated as mTOR, SREBP, PPARG, and AMPK). The inhibitory effect of conjugated linoleic acid (CLA) on milk fat synthesis in cows has been demonstrated in many studies, including in vitro and in vivo experiments. However, the impact of CLA on milk fat is limited to a single gene or pathway. This article reviews the possible relationships between various genes, pathways, and transcription factors. New synthesis mechanisms, such as thyroid hormone-inducible hepatic protein, methyltransferase complex containing methyltransferase-like 3, elongation of very long-chain fatty acid protein, and phosphatidate phosphatase 1 (abbreviated as THRSP, METTL3, ELOVL, and LPIN1), and new candidate genes involved in milk fat biosynthesis, including phosphatidylinositol 4-kinase type 2 alpha, solute carrier family 16 member 1, ATPase phospholipid transporting 8A2, vascular endothelial growth factor D, an inhibitor of DNA binding 1, and arachidonate 12-lipoxygenase (abbreviated as PI4K2A, SLC16A1, ATP8A2, VEGFD, ID1, and ALXO12), provide references for potential mechanisms of CLA-mediated regulation of milk fat metabolism.Abstract Milk fat synthesis in cows mainly includes the synthesis of short- and medium-chain fatty acids, the uptake, transport, and activation of long-chain fatty acids (LCFAs), the synthesis of triglycerides, and the synthesis of the genes, transcription factors, and signaling pathways involved. Although the various stages of milk fat synthesis have been outlined in previous research, only partial processes have been revealed. CLA consists of an aggregation of positional and geometric isomers of linoleic fatty acid, and the accumulated evidence suggests that the two isomers of the active forms of CLA (cis-9, trans-11 conjugated linoleic acid and trans-10, cis-12 conjugated linoleic acid, abbreviated as c9, t11-CLA and t10, c12-CLA) can reduce the fat content in milk by regulating lipogenesis, fatty acid (FA) uptake, oxidation, and fat synthesis. However, the mechanism through which CLA inhibits milk fat synthesis is unique, with most studies focusing only on the effects of CLA on one of the genes, transcription factors, or signaling pathways involved. In this study, we summarized the structure and function of classic genes and pathways (mTOR, SREBP, AMPK, and PPARG) and new genes or pathways (THRSP, METTL3, ELOVL, and LPIN1) involved in each stage of milk fat synthesis and demonstrated the interactions between genes and pathways. We also examined the effects of other substances (melanin, nicotinic acid, SA, etc.). Furthermore, we evaluated the influence of beta-sitosterol, sodium butyrate, Met arginine, and Camellia oleifera Abel on milk fat synthesis to improve the mechanism of milk fat synthesis in cows and provide a mechanistic reference for the use of CLA in inhibiting milk fat biosynthesis.