TRB3 Deletion Has a Limited Effect on Milk Fat Synthesis and Milk Fat Depression in C57BL/6N Mice.

Background: Regulation of the endoplasmic reticulum (ER) stress pathway is critical to mammary epithelial cell function throughout pregnancy, lactation, and involution. Treatment with -10, -12 conjugated linoleic acid (t10c12CLA) suppresses mammary lipogenesis and stimulates the ER stress pathway. The ER stress pathway includes tribbles pseudokinase 3 (TRB3), a protein that regulates cellular energy and insulin signaling.

Objectives: Our objective was to describe the effect of TRB3 deficiency on milk fat synthesis and determine if TRB3 deficiency protects against suppression of mammary lipogenesis.

Methods: First, mammary expression was observed throughout pregnancy and lactation using ancillary microarray data ( = 4/time point). Second, intake, litter growth, and milk clot fatty acid (FA) profile of knockout (KO) C57BL/6N mice were compared with wild-type (WT) and heterozygous (HET) mice throughout first ( ≥ 8/group) and second ( ≥ 6/group) lactation. Lastly, the interaction between genotype and 2 treatments that suppress mammary lipogenesis, t10c12CLA and high safflower oil (HO) diet, was investigated in a 2 × 2 factorial design ( ≥ 6/group).

Results: expression was higher during late pregnancy and lactation. KO and HET mice had lower feed intake, dam weight, and litter growth throughout first, but not second, lactation than WT mice. Treatment with t10c12CLA decreased litter growth (28%; < 0.0001) and feed intake (8%; < 0.0001) regardless of genotype. When fed the HO diet, KO mice had 17% higher mammary de novo synthesized FAs (<16 carbons; = 0.002) than WT mice. Mammary ER stress and lipogenic genes were mostly unaltered by deficiency.

Conclusions: Overall, TRB3 plays a minor role in regulating mammary lipogenesis, because deficiency had only a limited protective effect against diet-induced suppression of lipogenesis.