Oleic Acid Promotes Milk Fat Synthesis by Stimulating GPR40-Gα_q-PI3K/Akt-SREBP1-Dependent Fatty Acid Uptake.

Area of Science:

• * Molecular and cellular biology
• * Lipid metabolism
• * Mammalian lactation physiology

Background:

• * Milk fat is a key source of energy and essential fatty acids.
• * The precise mechanisms by which specific fatty acids influence milk fat synthesis are not fully understood.
• * Oleic acid, a common long-chain fatty acid (LCFA), plays a role in lipid metabolism.

Purpose of the Study:

• * To elucidate the role of oleic acid in mammary milk fat production.
• * To identify the molecular mechanisms by which oleic acid regulates triglyceride synthesis.
• * To investigate the GPR40-mediated signaling pathway in oleic acid-induced lipogenesis.

Main Methods:

• * In vitro studies using mammary epithelial cells treated with oleic acid.
• * siRNA-mediated knockdown and pharmacological inhibition of signaling pathway components.
• * In vivo studies in lactating mice administered a GPR40 antagonist.
• * Analysis of gene and protein expression, fatty acid uptake, and triglyceride accumulation.

Main Results:

• * Oleic acid upregulated sterol regulatory element-binding protein 1 (SREBP1) and fatty acid transporters (CD36, FATP4, FABP4).
• * Oleic acid enhanced fatty acid uptake and triglyceride synthesis via the GPR40-Gαq-PI3K/Akt-SREBP1 signaling axis.
• * GPR40 antagonism in vivo reduced milk fat content and mammary lipid deposition, confirming pathway relevance.

Conclusions:

• * Oleic acid significantly enhances milk fat synthesis in mammary epithelial cells.
• * The GPR40-Gαq-PI3K/Akt-SREBP1 cascade is a critical pathway mediating oleic acid's effects.
• * Findings provide molecular insights into dietary fatty acid regulation of milk fat production.