dinoprost and trans-10-cis-12-conjugated-linoleic-acid

Conjugated linoleic acids (CLAs) are a group of dietary fatty acids that are widely marketed as weight loss supplements. The isomer responsible for this effect is the trans-10, cis-12 CLA (10E12Z-CLA) isomer. 10E12Z-CLA treatment during differentiation of 3T3-L1 adipocytes induces expression of prostaglandin-endoperoxide synthase-2 (Cyclooxygenase-2; COX-2). This work demonstrates that COX-2 is also induced in fully differentiated 3T3-L1 adipocytes after a single treatment of 10E12Z-CLA at both the mRNA (20-40 fold) and protein level (7 fold). Furthermore, prostaglandin (PG)F(2α), but not PGE(2), is significantly increased 10 fold. In female BALB/c mice fed 0.5% 10E12Z-CLA for 10 days, COX-2 was induced in uterine adipose (2 fold). In vitro, pharmacological COX-2 inhibition did not block the effect of 10E12Z-CLA on adipocyte-specific gene expression although PGF(2α) was dose-dependently decreased. These studies demonstrate that PGF(2α) was not by itself responsible for the reduction in adipocyte character due to 10E12Z-CLA treatment. However, PGF(2α), either exogenously or endogenously in response to 10E12Z-CLA, increased the expression of the potent mitogen and epidermal growth factor (EGF) receptor (EGFR) ligand epiregulin in 3T3-L1 adipocytes. Blocking PGF(2α) signaling with the PGF(2α) receptor (FP) antagonist AL-8810 returned epiregulin mRNA levels back to baseline. Although this pathway is not directly responsible for adipocyte dependent gene expression, these results suggest that this signaling pathway may still have broad effect on the adipocyte and surrounding cells.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Cell Differentiation; Cyclooxygenase 2; Dietary Fats, Unsaturated; Dinoprost; Epidermal Growth Factor; Epiregulin; Female; Linoleic Acids, Conjugated; Mice; Mice, Inbred BALB C

The objective of this study was to evaluate the mechanism of action through which conjugated linoleic acid (CLA) beneficially affects reproduction. Lactating Holstein cows (n = 45, 20 +/- 1 DIM) were assigned to 1 of 3 treatments: 70 g/d of Ca salts of tallow (control); 63 g/d of lipid-encapsulated CLA providing 7.1 g/d of cis-9, trans-11 CLA and 2.4 g/d of trans-10, cis-12 CLA (CLA 75:25); or 76 g/d of lipid-encapsulated CLA providing 7.1 g/d each of cis-9, trans-11 and trans-10, cis-12 CLA (CLA 50:50). Supplements were top-dressed for 37 d, milk production and DMI were recorded daily, and blood samples were taken 3 times per week. At 30 +/- 3 DIM, ovulation was synchronized in all cows with a modified Ovsynch protocol, and on d 15 of the cycle cows received an oxytocin injection; blood samples were obtained frequently to measure 13,14 dihydro, 15-keto PGF2alpha. On d 16 of the cycle cows received a PGF2alpha injection and ovarian follicular aspiration was performed 54 h later. Follicular fluid was analyzed for fatty acids, progesterone, and estradiol. Endometrial biopsies were taken before and again near the end of the supplementation period for fatty acid analysis. The CLA resulted in decreased milk fat content of 14.1 and 6.1% at wk 5 of treatment of CLA 50:50 and CLA 75:25, respectively. There were no differences in energy balance or plasma nonesterified fatty acids; however, plasma IGF-I was greater in cows supplemented with CLA 50:50. The CLA isomers were not detectable in endometrial tissue, but cis-9, trans-11 CLA tended to be greater in follicular fluid of supplemented cows. Response to the oxytocin challenge was not different among treatments. Progesterone during the early luteal phase and the estradiol:progesterone ratio in follicular fluid tended to be greater in cows supplemented with CLA 50:50. Overall, these results indicate that short periods of CLA supplementation do not alter uterine secretion of PGF2alpha. The mechanism through which CLA affects reproduction may involve improved ovarian follicular steroidogenesis and increased circulating concentrations of IGF-I.

Topics: Animals; Calcium; Cattle; Dinoprost; Eating; Estradiol; Fats; Fatty Acids; Female; Follicular Fluid; Insulin-Like Growth Factor I; Lactation; Linoleic Acids, Conjugated; Milk; Ovulation Induction; Oxytocin; Pregnancy; Progesterone; Reproduction

Recent interest in conjugated linoleic acid (CLA) research stems from the well-documented anticarcinogenic, antiatherogenic, antidiabetic, and antiobesity properties of CLA in animal models. The objective of this study was to examine the effects of 2 CLA isomers (cis-9,trans-11 and trans-10,cis-12) on phorbol 12,13-dibutyrate (PDBu)-induced PGF2alpha production in cultured bovine endometrial (BEND) cells. Confluent BEND cells were incubated in the absence (control) or presence of 100 microM each of linoleic acid, cis-9,trans-11 CLA, or trans-10,cis-12 CLA for 24 h. After incubation, cells were rinsed and then stimulated with PDBu (100 ng/mL) for 6 h. Compared with untreated cells, PDBu stimulated PGF2alpha secretion (+25-fold) within 6 h. The increases in PGF(2alpha) secretion were paralleled by signifi-cant induction of prostaglandin endoperoxide synthase-2 (PGHS-2) mRNA (+63-fold) and protein (+1.6-fold) expression. In spite of stimulatory effects on PGHS-2 and peroxisome proliferator-activated receptor delta (PPARdelta) mRNA responses, CLA greatly decreased PGF2alpha production by PDBu-stimulated BEND cells. There was no evidence for PDBu or CLA modulation of PPARdelta protein synthesis in cultured BEND cells. Results indicated that CLA modulation of PGF2alpha production by BEND cells was not mediated through PGHS-2 or PPARdelta gene repression.

Topics: Animals; Cattle; Cells, Cultured; Cyclooxygenase 2; Dinoprost; DNA Primers; Endometrium; Female; Linoleic Acids, Conjugated; Phorbol 12,13-Dibutyrate; PPAR delta; Prostaglandin-Endoperoxide Synthases