This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Divergent Regulation of Mammary Lipogenesis by trans-10, cis-12 and cis-9, trans-11 CLA Isomers Is Determined by Receptor-Specific Signaling
Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Animal Nutrition and Efficient Feeding, College of Animal Science and Technology, Shandong Agricultural University, Tai’an 271017, China
*
Authors to whom correspondence should be addressed.
Animals 2025, 15(23), 3418; https://doi.org/10.3390/ani15233418
Submission received: 21 October 2025
/
Revised: 15 November 2025
/
Accepted: 25 November 2025
/
Published: 26 November 2025
(This article belongs to the Section Animal Physiology)
Simple Summary
Milk fat is an important part of dairy nutrition and economics, but its production can be reduced by certain dietary components. This study examined how two similar fatty acid molecules called CLA isomers affect fat-making processes in mammary gland cells from goats. Although these isomers have nearly identical structures, they produce very different effects. One isomer (t10c12-CLA) strongly suppressed the production of proteins needed to make milk fat and damaged cellular energy factories called mitochondria, while the other isomer (c9t11-CLA) had much milder effects and preserved normal cellular function. By investigating the underlying mechanisms, researchers discovered that t10c12-CLA works through a specific cellular receptor called GPR40 to trigger these dramatic changes, whereas c9t11-CLA does not strongly activate this same pathway. Importantly, blocking GPR40 reversed most of the damaging effects of t10c12-CLA. These findings explain why structurally similar molecules can have dramatically different biological effects and suggest new strategies for controlling milk composition through targeted nutritional approaches in dairy farming.
Abstract
Conjugated linoleic acid (CLA) isomers exhibit distinct biological activities in lipid metabolism, yet their roles in regulating mammary lipogenesis remain poorly understood. Understanding how individual CLA isomers influence lipid synthesis is essential for improving milk fat quality and developing targeted nutritional strategies. We assessed the effects of trans-10, cis-12 (t10c12-CLA) and cis-9, trans-11 (c9t11-CLA) isomers on lipid synthesis in goat mammary epithelial cells and investigated fatty acid receptor involvement. t10c12-CLA significantly suppressed key lipogenic proteins (FASN, ACACA, and SREBP-1) and impaired mitochondrial activity, as evidenced by reduced mitochondrial membrane potential, ATP/ADP ratio, and PGC-1α expression. Both isomers paradoxically increased lipid droplet accumulation; for t10c12-CLA, this phenomenon resulted from compensatory metabolic shifts due to weakened mitochondrial function. Critically, GPR40 inhibition reversed the antilipogenic effects and mitochondrial impairment caused by t10c12-CLA, establishing GPR40 as the key mediator. In contrast, c9t11-CLA had milder effects and preserved mitochondrial activity, with no definitive receptor dependence established. Transcriptomic analysis confirmed isomer-specific gene expression patterns, with t10c12-CLA broadly affecting lipid metabolism and mitochondrial pathways in a GPR40-dependent manner. These findings reveal that the divergent effects of CLA isomers are dictated by differential receptor engagement, providing insights for precision nutritional strategies in dairy production.
