Rat mammary-gland acetyl-coenzyme A carboxylase. Interaction with milk fatty acids

Abstract

1. Highly purified rat mammary-gland acetyl-CoA carboxylase was inhibited by milk obtained from rats 12h after their young were weaned. 2. All the inhibitory activity was found in the particulate fraction (R(105)) obtained on centrifuging the milk. It could be extracted from milk fraction R(105) with acetone and identified as a complex mixture of non-esterified fatty acids, present in high concentration (nearly 10mm) in the milk. 3. Inhibition of acetyl-CoA carboxylase was observed at low concentrations (0.2-20mum) of several of these fatty acids when fresh fully active enzyme was used. Enzyme that had been partly inactivated by aging, or by storing in the absence of citrate, was stimulated by low concentrations but inhibited by high concentrations of fatty acids. 4. Various experiments suggested that fatty acids produce irreversible inactivation of acetyl-CoA carboxylase. 5. The effects of palmitoyl-CoA on mammary-gland acetyl-CoA carboxylase were found to resemble those of fatty acids, except that palmitoyl-CoA was effective at lower concentration. 6. The effect of milk fraction R(105) was tested on six other enzymes previously shown to decline to various extents after weaning. Although several of these enzymes were affected by unfractionated milk fraction R(105), none was significantly inhibited by the acetone extract or by low concentrations of lauric acid. 7. The findings are consistent, both qualitatively and quantitatively, with a regulatory mechanism whereby milk fatty acids shut off fatty acid synthesis in the mammary gland after weaning by inhibiting acetyl-CoA carboxylase.

SCD1 Alters Long-Chain Fatty Acid (LCFA) Composition and Its Expression Is Directly Regulated by SREBP-1 and PPARγ 1 in Dairy Goat Mammary Cells

“…The increase in C16:1 and C18:1 at the expense of C16:0 and C18:0 with the overexpression of SCD1 is consistent with previous reports in other species (Rogowski et al, ; Wang et al, ). Evidence suggested that medium and long chain FA are potent inhibitors of ACACA in the mammary gland, especially palmitoyl CoA (Miller et al, ; Lunzer et al, ). Thus, one plausible explanation for the lower ACACA mRNA level along with the increase in saturated fatty acids when SCD1 was deleted is that the increase in saturated FA, specifically C18:0, inhibited the transcription and activity of ACACA (Neville and Picciano, ).…”

Integration of metabolism in tissues of the lactating rat

“…Pyruvate dehydrogenase determines the proportion of glucose carbon that is converted into lactate or lipid (acetyl-CoA) [35,36] and alterations in the activity of this enzyme play a key role in the regulation of glucose metabolism in the gland. Utilization of acetyl-CoA generated by cleavage of citrate in the cytosol is controlled by acetyl-CoA carboxylase, which is activated by citrate and Mg'+, and inhibited by certain fatty acids or their acyl-CoA esters in mammary gland [37,38]. One role of the pentose phosphate pathway is to supply NADPH for fatty acid synthesis and this pathway is present in high activity in the lactating gland.…”

Chain-length dependency of interactions of medium-chain fatty acids with glucose metabolism in acini isolated from lactating rat mammary glands. A putative feed-back to control milk lipid synthesis from glucose

“…Presumably, in most situations, the non-esterified medium-chain fatty acids are rapidly converted into fatty acyl-CoA and esterified to triacylglycerols for subsequent secretion in milk. Rat milk, however, contains a measurable amount of non-esterified fatty acids (2.06 mg/ml of milk), of which about 12 % or 1.2 mm are medium-chain fatty acids (C6-C10) [32]. It has been demonstrated that this non-esterified fatty acid fraction can irreversibly inactivate mammary-gland acetyl-CoA carboxylase in vitro [32].…”

“…Rat milk, however, contains a measurable amount of non-esterified fatty acids (2.06 mg/ml of milk), of which about 12 % or 1.2 mm are medium-chain fatty acids (C6-C10) [32]. It has been demonstrated that this non-esterified fatty acid fraction can irreversibly inactivate mammary-gland acetyl-CoA carboxylase in vitro [32]. Little milk accumulates in rat mammary gland during suckling; however, on removal of the pups for 12 h milk accumulates to about 50% of the gland weight [32].…”

“…It has been demonstrated that this non-esterified fatty acid fraction can irreversibly inactivate mammary-gland acetyl-CoA carboxylase in vitro [32]. Little milk accumulates in rat mammary gland during suckling; however, on removal of the pups for 12 h milk accumulates to about 50% of the gland weight [32]. it is not known whether under these circumstances the concentrations of medium-chain fatty acids also increase in mammary tissue, but it is reasonable to speculate that the observed inhibition ofglucose conversion into lipid may represent a physiological feed-back mechanism to conserve glucose when milk accumulates in the mammary gland.…”