1,2‐sn‐Diacylglycerol accumulates in choline‐deficient liver

Abstract

Choline deficiency is associated with triacyiglycerol accumulation in the liver, and is the only nutritional state known to trigger hepatic cancer spontaneously. In two different experiments, rats were pair-fed for 6 weeks with control (0.2% choline), or choline-deficient (CD) (0.002% choline) diets. Hepatic choline and phosphocholine declined in CD animals to 54% and 16~ of control levels, respectively. In control livers, 1,2-sn-diacylglycerol (I,2-sn-DAG) concentration was (in nmol/g wet wt) 144 (+25; mean+SE); while in CD livers it was 792 (+ 140) in the first experiment. In the second experiment the values were 375 (+ 26) and 1147 (+ 74), respectively. 1,2-sn-DAG, a precursor of triacylglycerol, is an endogenous activator of protein kinase C (PKC). PKC is the presumed site of action of the tumor-promoting phorbol esters. We suggest that the 1,2-sn-DAG accumulating in CD liver could bind PKC, altering its activity, and thus contribute to the carcinogenic effect of CD diets.

Maternal betaine supplementation affects fetal growth and lipid metabolism of high-fat fed mice in a temporal-specific manner

“…However, betaine may still contribute to the PC pool by providing methyl groups for the sequential methylation of phosphatidylethanolamine to form PC via the PEMT pathway 37 . Therefore, the possibility that BS alters PC signaling 38 , 39 which influences other nutrient sensing mechanisms such as the mechanistic target of rapamycin (mTOR) to affect placental transport 16 cannot be ruled out.…”

Choline prevents fetal overgrowth and normalizes placental fatty acid and glucose metabolism in a mouse model of maternal obesity

“…Data on placental metabolite concentrations suggest that maternal HF feeding decreased placental phosphatidylcholine content which was reversed by choline supplementation. Phosphatidylcholine deficiency has been shown to activate uncontrolled cell growth by increasing the accumulation of the second messenger diacylglycerol which activates the PKC-mediated mitogenic pathways [22, 23]. Further studies are needed to validate whether maintaining the level of phosphatidylcholine is indeed important for the attenuation of placental growth signals and improvement of fetal growth outcomes.…”

“…Since maternal obesity increases placental lipid accumulation which is associated with fetal adiposity [21], increasing the availability of choline may attenuate placental lipid overload and reduce lipid transport to the fetus. Furthermore, phosphatidylcholine deficiency activates the mitogenic pathway involving protein kinase Cs (PKCs) and promotes cell proliferation [22, 23]. Maintaining choline status may then prevent excessive placental and fetal growth.…”

Choline Inadequacy Impairs Trophoblast Function and Vascularization in Cultured Human Placental Trophoblasts

“…Activation of PKC signaling may be a pivotal upstream event in response to choline inadequacy, which results in trophoblast dysfunction. The activation of PKC signaling in choline inadequacy may arise from increases in the polyunsaturated DAG species SAG and SDG, potent activators of PKC that can be formed as an intermediates of the CDPcholine pathway or as by-products of PC catabolism (Blusztajn and Zeisel, 1989;da Costa et al, 1993). Based on the gene expression profile of the choline metabolizing enzymes, the increase in these DAG species may arise from an attempt to synthesize more PC via the CDP-choline pathway.…”