Effect of an alpha-linolenic acid-rich diet on rat mammary tumor growth depends on the dietary oxidative status.

To investigate whether the oxidative status of an 18:3(n-3) polyunsaturated fatty acid (PUFA)-enriched diet could modulate the growth of chemically induced rat mammary tumors, three independent experiments were performed. Experiments I and II examined the variation of tumor growth by addition of antioxidant (vitamin E) or a prooxidant system (sodium ascorbate/2-methyl-1,4-naphthoquinone) to a 15% linseed oil diet rich in 18:3(n-3). Experiment III addressed the role of PUFA in the tumor growth modulation by vitamin E. For this purpose, we compared the effect of vitamin E in 15% fat diets containing a high level of 18:3(n-3) (linseed oil, high-PUFA diet) or devoid of 18:3(n-3) (hydrogenated palm/sunflower oil, low-PUFA diet). In Experiments I-III, tumor growth increased in the presence of vitamin E compared with control (without vitamin E). Furthermore, it decreased when prooxidant was added. In contrast, no difference was observed when the diet was low in PUFA, suggesting that sensitivity of PUFA to peroxidation may interfere with tumor growth. This observation was supported by growth kinetic parameter analysis, which indicated that tumor growth resulted from variations in cell loss but not from changes in cell proliferation. These data show that, in vivo, PUFA effects on tumor growth are highly dependent on diet oxidative status.

Dietary (n-6) polyunsaturated fatty acids affect beta-adrenergic receptor binding and adenylate cyclase activity in pig adipocyte plasma membrane.

The effect of dietary (n-6) polyunsaturated fatty acids (sunflower oil) on pig adipocyte beta-adrenoreceptor and adenylate cyclase activity was examined. Two adipose sites (subcutaneous and perirenal) were compared. The existence of two affinity classes for beta-adrenoreceptors was evidenced. Adenylate cyclase stimulation by isoproterenol was higher in the perirenal fat than in the subcutaneous fat, in parallel to a higher beta-adrenoreceptor density. When sunflower oil was included in the diet, the adenylate cyclase response to beta-agonists was greater, particularly in perirenal fat, as was the affinity of the adrenoreceptors in their high affinity state. However, the number of beta-adrenoreceptors was lower, suggesting that these are spare receptors. Adenylate cyclase stimulation by 5'-guanylylimidophosphate also revealed site- and diet-specific variations indicating alterations at the Gs-protein level. The adenylate cyclase catalytic activity (reflected by the forskolin-stimulated response) in the control group was higher in the subcutaneous fat than in the perirenal fat. In the sunflower oil-fed pigs, the catalytic activity was greater in the perirenal fat relative to controls, leading to similar values in both adipose tissues of sunflower oil-fed pigs. This indicates that the cyclase catalytic subunit activity also depends on the anatomical site of the fat deposit and is influenced by the diet as well. Correlation between these changes in the adenylate cyclase system are discussed in relationship with alterations in the plasma membrane structure.

Effects of castration, dietary fat and adipose tissue sites on adipocyte plasma-membranes cyclic AMP phosphodiesterase activity in the pig.

1. cAMP Phosphodiesterase activity and kinetic parameters (Km and Vmax) were measured in subcutaneous and perirenal adipocyte plasma membranes from Large White male and castrated pigs. The animals were fed a control low fat diet or a sunflower diet enriched with linoleic acid (C18:2 n-6). 2. Phosphodiesterase activity, low Km and Vmax were lowered by castration. 3. In animals fed the sunflower diet, phosphodiesterase activity decreased without affecting either Km or Vmax. 4. Phosphodiesterase activity was higher in perirenal sites than in subcutaneous ones, particularly in male pigs. This may be explained by a lower Km or a higher cAMP phosphodiesterase affinity to cAMP in perirenal sites. 5. Theophylline was a potent inhibitor of phosphodiesterase activity principally in perirenal sites. 6. The intermediate role of cAMP phosphodiesterase in adenylate cyclase activity and lipolytic processes is discussed.

Specific alterations in different adipose tissues of pig adipocyte plasma membrane structure by dietary lipids.

The effect of dietary n-6 polyunsaturated fatty acid content on pig adipocyte plasma membrane was studied with two types of adipose tissues: subcutaneous backfat layer and perirenal fat. When pigs were fed a diet containing 15 percent sunflower oil, the n-6 polyunsaturated fatty acid content in the membranes increased in both tissues parallel to a decrease in the n-9 monounsaturated fatty acid content. An increase in membrane fluidity measured by fluorescence polarization was observed particularly in subcutaneous tissue, in spite of a higher level of some membrane rigid components: the sphingomyelin/phosphatidylcholine ratio was increased in the subcutaneous tissue, whereas the cholesterol/phospholipid ratio was increased in the perirenal one. The latter results gave evidence for a depot-dependent modification in the membrane structure by dietary lipids.

Effect of dietary fat on phospholipid class distribution and fatty acid composition in rat fat cell plasma membrane.

The effect of dietary fats on phospholipid class distribution and fatty acid composition was studied in rat fat cell plasma membrane. Three groups of male Wistar weanling rats were fed for 8 wk three diets differing in the amount and nature of the fats: 1.5% sunflower oil (low fat control; LFC), 10% sunflower oil (high fat, unsaturated; HFU), 1.5% sunflower oil + 8.5% cocoa butter (high fat, saturated; HFS). Plasma membranes were prepared from epididymal adipocytes. The amount and type of dietary fat significantly altered membrane phospholipid distribution. Phospholipid content was lowered with HFU as compared to LFC or HFS diets, but no changes were observed for cholesterol. Phosphatidylinositol (PI) and phosphatidylserine (PS) were less affected by dietary changes than were other phospholipid classes. Major changes were detected for phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) contents. No large changes in PC and PE fatty acid compositions were observed between the LFC and HFS groups, but the HFU diet induced several changes. Correlations with plasma membrane 5'-nucleotidase activities are discussed.