Low milk fat syndrome.

Abstract

LOW MILK FAT SYNDROME E.F. ANNISON Summarv proporMilk fat production in well-fed cows may fall sharply if the t i o n o f roughage in the diet is too low, or if the roughage is finely ground. Although mainly associated with the feeding of high l e v e l s o f starch-rich the low milk fat syndrome may occur in herds concentrates, grazing lush green feeds without adequate supplementary roughage. The primary cause of the syndrome is increased production of propionate in the rumen, The raised glucose which enhances gluconeogenesis. supply stimulates insulin secretion, which leads to increased utilisation of acetate for adipose tissue synthesis and accounts for the reduction in blood acetate concentration. Circulating triacylglycerol concentrations may also fall, and extraction rates by the mammary of triacylglycerol gland decline significantly. The reduced supply of acetate, and lowered uptakes of triacylglycerol by the mammary gland largely accounts for the fall in milk fat production, since the two substrates are the major precursors of milk fat. I. INTRODUCTION Milk fat production in well-fed cows may fall sharply if the ratio of digestible carbohydrate to roughage in the ration is high (Van Soest and Allen 1959; Storry and Sutton 1969), or if the roughage in the ration is finely ground (Powell 1939). ' Oils rich in polyunsaturated fatty acids may also depress milk fat levels, but responses to all types of diet are influenced by level and frequency of feeding, stage of lactation, level of milk production and condition of the animal (see Davis and Brown 1970). The recognition in the 1950's of the major role of acetate in both bovine mammary gland metabolism (McClymont 1951) and in milk fat synthesis (see Annison 1983) led to the view that decreased acetate supply is the primary factor in the low milk fat `syndrome. several reports of Indeed, reduced ruminal acetate concentrations in affected animals gave support to this hypothesis (see Van Soest 1963). More comprehensive studies, however, revealed that ruminal acetate levels in low roughage fed animals were often unchanged but the ratio of acetate to propionate (Q/C3 ratio) was found to be closely related to milk fat concentrations (see Armstrong and Prescott 1971). The view that increased propionate production, and not decreased is responsible for the low milk fat syndrome was first put acetate supply 3 forward by McClymont and Valiance (1962), who showed that the intravenous infusion of glucose into lactating cows reduces milk fat output. These workers suggested that the enhanced gluconeogenesis which accompanies incre,ased ruminal propionate production on low roughage diets suppresses the mobilisation of fat from adipose tissue and results in the lowered availability of plasma triacylglycerides for milk fat synthesis. Department of Animal Husbandry, University of Sydney, Camden, New South Wales 2570 Comprehensive metabolic st,udies in cows which had responded to high starch:low roughage diets by producing milk of low fat content confirmed the 1974). key role of propionate in the low milk fat syndrome (Annison et al. production. Low c2 /c3 ratios were attributable to increased propionate Gluconeogenesis was increased, and the higher levels of circulating glucose were associated with significant falls in the concentrations of acetate and 3-hydroxybutyrate. The most convincing explanation of the adverse e f f e c t s o f raised glucose supply on milk fat levels is. that increased circulating levels of glucose stimulates insulin secretion.' This, in turn, promotes lipogenesis from acetate in adipose tissue, and suppresses triacylglycerol mobilisation from adipose tissue. The end results are lowered blood levels of the two In the absence major precursors of milk fat, acetate and triacylglycerol. o f increases in either mammary blood flow, or the avidity of the mammary gland for these substrates, milk fat synthesis falls (Annison et al. 1974). An alternative explanation of the aetiology of dr ome is that diets which enhance ruminal propionate vitamin B12 synthesis, and lead to the accumulation the liver (Frobish and Davis 1977). Methylmalonyl fatty acid synthesis. the low milk fat synproduction may reduce of methylmalonyl CoA in CoA is known to inhibit In this review aetiology of the low milk fat syndrome is discussed in relation to current knowledge of milk fat synthesis. II. MILK FAT SYNTHESIS IN RUMINANTS 1 lactating The precursors of milk fat are extracted from blood by the mammary gland. Quantitative data have been obtained by combining arteriovenous (AV) difference measurements with isotope dilution (see Annison 1983). All of the short and medium chain length fatty acids (C4-C14) and part of the palmitate which appears in milk fat triacylglycerols are synthesised The de novo in the mammary gland from acetate a n d 3-hydroxybutyrate. remainder of the palmitate, and all of the stearate, oleate, linoleate and longer chain fatty acids are transferred intact into the mammary gland from circulating triacylglycerols, which are hydrolysed in the mammary gland capillary bed (see Annison 1983). Carbon balance data for the production of milk fat in the goat, cow and sheep are shown in Table 1. Table 1. Carbon balance(%) for the production of milk fat in fed lactating ruminants (King et al., 1985) High starch:low roughage diets may result in reduced ruminal bioThe suggestion hydrogenation and increased levels of trans fatty acids. lipoprotein that these fatty acid isomers may cause derangement of metabolism and contribute to the low milk fat syndrome (see Davis and Brown 1970) has not been ruled out by studies showing that labelled cis and trans isomers of octadecenoate are incorporated into milk fat at similar rates Lipoprotein triacylglycerols rich in trans (Bickerstaffe et al. 1972). structural fatty acids, or other partial hydrogenation products may have configurations that reduce their susceptibility to lipoprotein lipase in The 50% fall in the extraction rate (A-V/A x mammary tissue capillaries. 100) of circulating triacylglycerol observed in animals producing milk of low fat content (Annison et al. 1974) is consistent with this hypothesis. III. QUANTITATIVE STUDIES ON GLUCOSE AND VOLATILE FATTY ACID METABOLISM IN COWS PRODUCING MILK OF LOW FAT CONTENT The low milk fat syndrome was induced in two Friesian cows by changing Milk fat content the concentrate:hay ratio in their diets from 5:3 to 17:2. Changes in declined from 3.0 and 2.3 to 2.3 and 1.5 g/100 g respectively. glucose, acetate and long chain fatty acid metabolism in the mammary gland, and in the whole animal were examined by AV difference and isotope dilution procedures (Annison et al. 1974). (a) Rumen VFA metabolism On transfer to the low roughage diet, the ratio of acetate plus butyrate to propionate in rumen contents changed from a mean ratio of 2.8 to concentration. Butyrate 1.4, without a significant change in acetate concentrations fell from a mean level of 21 mmol/l to 10 mmol/l. (b) Mammary gland metabolism Arterial blood concentrations of glucose increased, acetate and 3The hydroxybutyrate levels decreased and triacylglycerol was unchanged. proportion of triacylglycerol taken up from arterial blood by the mammary coupled with the reduced availgland fell by about 50X, and thistfactor, ability of acetate and 3=hydroxybutyrate, accounted for the reduction in milk fat production. (C> Glucose metabolism The mean entry rate of glucose into the circulation rose by 31% and the mean contribution of glucose to total body CO2 production increased from 5 to 11% when the low roughage diet was fed. (d) Acetate metabolism Arterial blood acetate concentrations fell from a mean value of 8.1 mg/100 m l to 4.1 mg/100 ml when the animals were fed the low roughage ration, reflecting a decrease of 55% in the mean acetate entry rate. The corresponding reduction in the contribution of acetate to total CO2 production was 55%. tively The large fall in acetate entry rate was unexpected in view of relaunchanged rumen acetate concentrations. A partial explanation was afforded by the ' three-fold fall in endogenous acetate production by mammary gland, if other tissues responded in the same way. (e) Long chain fatty acid metabolism the In the one cow studied, clear evidence was obtained of reduced ruminal biohydrogenation when the animal was fed low roughage:high concentrate rations. Total unsaturated fatty acids in arterial triacylglycerols increased from 37% on the high roughage diet to 55% on the low roughage diet Corresponding values for the proportion of trans.isomers in the octadecenoate fraction of arterial triacylglycerols inked from 22 to 56% respectively. l IV. SIGNIFICANCE OF THE ACETATE:PROPIONATE RATIO IN THE RUMEN Armstrong and Prescott (1971) collated data from thirteen experiments on lactating cows in which ruminal volatile fatty acid (VFA) concentrations were correlated with milk fat concentrations. Although a range of diets was acetate:propionate ratios below 3.0 were invariably associated with fed, milk fat depression, which increased as the ratio decreased. The elegant energy balance studies of W.P. Flatt, summarised by Annison and Armstrong (19701, clearly show that adipose tissue is deposited at the expense of milk fat as the acetate:propionate ratio falls (Table 2). Table 2. Data relating to the mean energy balances of cows eating rations containing 40, 60 or 80% concentrates . ZYield of milk x fat content. Assuming all body tissue energy to be fat of calorific value 9.21 k Cal/kg. V. EFFECTS OF INSULIN STATUS ON MILK FAT PRODUCTION McClymont and Valiance (1962) showed that the intravenous infusion of The authors glucose into lactating cows reduced milk fat concentrations. hypothesis to account for this finding was that increased insulin secretion the precursuppressed the release from adipose tissue of free fatty acids, sors of circulating triacylglycerols. This study was remarkably perceptive, since recent findings at that time that acetate, and not glucose, is the major source of milk fatty acid carbon dominated thinking on milk fat synthesis (see Annison 1983). Support for the view that the low fat syndrome was infusion of glucose or insulin in adipose tissue (Rao et al. al. 1972). increased insulin secretion is, a major factor provided by the finding that the intravenous stimulated the activity of lipoprotein lipase 1973), but not in mammary tissue (Benson et in A recent study by Laarveldt and Chaplin (1985) in which mixtures of insulin and glucose were intravenously infused into lactating cows failed to demonstrate any effects on milk fat synthesis. The 2 hour period over which insulin was administered, however, may have been too short to effect measurable changes in lipid metabolism. D. Leenanuruksa and G.H. McDowell (personal communication) have studied the effects of glucose and insulin on milk fat production in lactating ewes I The ewes were given treated with alloxan to eliminate insulin secretion. insulin intravenously at rates sufficient to maintain a mild hyperglycemia. Milk yield was unaffected, but milk fat levels rose significantly, in contrast with the'situation in intact lactating cows, where the intravenous infusion of glucose to raise blood levels resulted in a sharp fall in milk fat concentration (McClymont and Valiance 1962). Evidence that the main role of insulin the aetiology of the low milk fat syndrome is the diversion of acetate into adipose tissue was obtained in experiments in which glucose and acetate were infused into lactating ewes (Hough 1982). Glucose, or glucose and acetate were infused intravenously for 4 d at rates equivalent to 37.5% and 50% respectively of calculated irreversible loss rates. As expected from earlier work, glucose infusions lowered milk fat levels, but when acetate was infused with glucose, milk fat levels were substantially restored (Table 3). Table 3. Effects of intravenous infusions of glucose and acetate on milk yields and milk fat levels in 5 ewes (mean values for final 2 d of each treatment, with saline controls) VI. VITAMIN Bl2 AND THE LOW MILK FAT SYNDROME Frobish and Davis (1977) proposed that a contributory factor in the aetiology of the low milk fat syndrome was impaired propionate metabolism stemming from high levels of propionate production and decreased vitamin to Propionate is metabolised in the liver B12 synthesis in the rumen. The latter methylmalonyl CoA, which is in turn converted to succinyl CoA. conversion requires the enzyme methylmalonyl CoA isomerase and a coenzyme form of vitamin B12 as cofactor. High grain:low roughage diets may reduce vitamin B12 production (Walker and Elliott 1972), and in B12 deficiency the intermediate methylmalonate accumulates. Methylmalonate has been shown to inhibit fatty acid synthesis from acetyl CoA and malonyl CoA (Cardinale et al. 1970). Experimental evidence that vitamin B12 deficiency may cDntri't>ute t o milk fat production is equivocal. Frobish and Davis (1977) found reduced that 3 out of 7 cows fed a high grain:low roughage ration responded to Later injections of hydroxocobalamin by increasing milk fat production. work by Elliott et al. (1979) and Groom et al. (1981) failed to confirm these findings. VII. PREVENTION OF LOW MILK FAT SYNDROME McClymont (1951) discussed the relationships between the type and In quantity of roughage and the fat content of the milk of grazing COWS. green NSW, low milk fat levels occurred in dairy herds grazing young, The occurrence of the syndrome in herbage without access to long roughage, cows grazing young green oats (fibre content 507%) had long been recognised. the minimum Experience in NSW suggests that when herbage is the sole feed, roughage content should be about 20% to avoid milk fat depression. Roughage chopped to less than 1 cm is ineffective in preventing milk fat depression, so it is important to feed supplementary roughage in long forme When concentrates are fed, the ideal ratio of concentrates to roughage This feeding system, in addition to maintaining is about 60:40 (Kay 1969). normal milk fat levels, ensures maximum fertility, Increased calving intervals have been reported at higher proportions of concentrates (Kay 1969). Where there is limited grazing and `intakes of starch rich concentrates are high, a minimum of 5 kg hay/d, or the equivalent, is recommended in order to avoid milk fat depression. I VIII, DISCUSSION There is overwhelming evidence that the key factor in the aetiology of the low milk fat syndrome is a rumen fermentation which gives rise to a Although there is strong Q/C3 of below 3.0 (Armstrong and Prescott 1971)e indirect evidence that a changed insulin status stemming from enhanced gluconeogenesis reduces the availability to the mammary gland of acetate and direct evidence of the the main precursor,s of milk fat, triacylglycerol, role of insulin has not yet been reported. In most instances, reduced acetate supply to the mammary gland is the major factor causing milk fat depression (Pethick and Lindsay 1982). Engvall (1980) has shown that forty three field cases of cows producing milk of low fat content, the milk fatty acids showing significant reduction were In fed animals, those synthesised from acetate and D(-) 3-hydroxybutyrate. 3-hydroxybutyrate is derived mainly from ruminal butyrate, and conditions in the rumen which favour propionate production often suppress butyrate formation, acetate The significance of the apparent reduction in endogenous production in cows producing milk of reduced fat content (Annison et al, 1974) remains unclear, Pethick et al. (1981) suggested that endogenous acetate production is largely unaffected by physiological or nutritional StateS, King et ale (1985) have,shown that endogenous acetate production by the mammary gland of the ewe increases linearly with milk yield, but data are required for other tissues in animals producing milk of low fat content. The possible involvement of B12 deficiency in the low fat syndrome should always be considered in regions where cobalt deficiency is suspected, The reduced mammary extraction rate of triacylglycerols in cows 1974) merits induced to produce milk of low fat content (Annison et ale Although acetate shortage appears to be the dominant feature further studye o f the low fat syndrome, the possibility that triacylglycerols r i c h i n fatty acids are less readily hydrolysed by lipopartially hydrogenated protein lipase in mammary capillaries is of considerable interest, Changes in systems of payment for milk which minimise the returns for milk fat might lead to a reassessment of priorities in dairy cow feeding. If at some future date milk of low fat content becomes acceptable to marketing authorities, the producer must take into account possible reductions in fertility that appear to be associated with low roughage rations (Kay 1969). 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