Isomers of Conjugated Linoleic Acid Differ in Their Effects on Angiogenesis and Survival of Mouse Mammary Adipose Vasculature

Abstract

Dietary conjugated linoleic acid (CLA) is a cancer chemopreventive agent that has been shown to inhibit angiogenesis in vivo and in vitro, and to decrease vascular endothelial growth factor (VEGF) and Flk-1 concentrations in the mouse mammary gland. To determine which isomer mediates the antiangiogenic effects of CLA in vivo, the effects of diets supplemented with 5 or 10 g/kg c9,t11- or t10,c12-CLA isomers were compared in CD2F1Cr mice. Both isomers inhibited functional vascularization of a matrigel pellet in vivo and decreased serum VEGF concentrations; the t10,c12 isomer also decreased the proangiogenic hormone leptin (P < 0.05). Additionally, the t10,c12 isomer, but not c9,t11-CLA, rapidly induced apoptosis of the white and brown adipocytes as well as the preexisting supporting vasculature of the mammary fat pad (P < 0.05). Independent of this isomer-specific adipose apoptotic effect, both isomers induced a rapid and reversible decrease in the diameter of the unilocular adipocytes (P < 0.05). The ability of both CLA isomers to inhibit angiogenesis in vivo may contribute to their ability to inhibit carcinogenesis. Moreover, we propose that each CLA isomer uniquely modifies the mammary stromal "soil" in a manner that is useful for chemoprevention of breast cancer.

Conjugated linoleic acid induces apoptosis of murine mammary tumor cells via Bcl-2 loss

“…It and the predominant natural isomer c9,t11-CLA, have been studied most extensively since they are each available commercially at relatively high purity. Although both CLA isomers were found to be equally efficacious in inhibiting rat mammary carcinogenesis [31] and angiogenesis [32], t10,c12-CLA is the more potent isomer in most in vitro studies. In TM4t mammary tumor cells, for example, we found that t10,c12-CLA is approximately five times more potent than c9,t11-CLA in decreasing viable cell number.…”

Anti-Angiogenic Effects of Conjugated Docosahexaenoic Acidin Vitroandin Vivo

“…This anti-angiogenic effect is likely to have been related to tumor suppression by CDHA, 18) and may also have been related to the anti-obesity effect of CDHA, 15) since angiogenesis has been associated with an increase in white adipose tissue. 40) The DAS assay showed that neovascularization of the mouse subcutaneous tissues, which was triggered by DLD-1 cells, was effectively inhibited by the oral administration of CDHA (Fig. 6).…”

“…DHA, CLA, -T3 and thalidomide were used as positive controls of this effect. 33,[36][37][38][39][40] Thalidomide is used as a therapeutic agent for angiogenesis disease.…”

“…This suggests that the conjugated double bond in CDHA was important for anti-angiogenesis; in this context, it is of note that conjugated linoleic acid exerted an anti-angiogenic effect, whereas linoleic acid did not do so. 39,40) The mechanism for angiogenesis inhibition by CDHA in vitro was investigated by observing the cellular morphology. Inhibition of the BAEC growth caused by CDHA was accompanied by marked change in the cellular morphology.…”

Effets de l’acidetrans-10,cis-12linoléique sur le métabolisme des lipides dans le foie chez la souris C57BL/6

“…Les effets biologiques attribués aux CLA sont nombreux, souvent mal compris, voire contradictoires. Les CLA sont décrits comme des modulateurs de la réponse immunitaire [1,2], comme possédant des propriétés anticancé-reuses [3,4], anti-athérogéniques [5,6], antidiabétiques [7,8] ou encore comme responsables d'une augmentation de la résistance à l'insuline [9,10]. L'effet réducteur des CLA sur la masse grasse décrit dans plusieurs modèles animaux [11][12][13][14] apparaît très spectaculaire, même si les études menées chez l'Homme ne sont pas aussi démonstratrices [15,16].…”