Fat deposition in ruminants: what drives lipogenesis in sheep and cattle

Why the pattern of fat growth mattered#

Thornton and Tume start from a long-recognised pattern: protein builds up in cattle and sheep in a close-to-straight line as animals grow, but fat accumulation takes off once a threshold empty bodyweight is reached, described as around 300 kg in cattle and around 30 kg in sheep. Before that point animals lay down comparatively little fat; after it, fat deposition accelerates sharply. The authors call this threshold the point of physiological maturity, and stress it is not tied to weaning, to any change in diet, or to puberty.

Breed, sex and management all shift this pattern. Larger, late-maturing breeds begin the rapid fattening phase at heavier bodyweights than smaller, early-maturing animals, a comparison explored further in the summary on late-maturing cattle carcase fat. Dairy cattle are described as leaner overall but carrying more internal fat around the omentum, kidneys and digestive tract, and less fat under the skin, compared with beef cattle. Some sheep breeds selected for fecundity and milking ability carry heavier internal fat deposits than breeds selected mainly for meat production. Castrates, the animals most studies are based on, are intermediate between entire males (leaner) and females (fatter). The review treats this as evidence of a genuine repartitioning of nutrients toward fat once an animal passes its particular maturity threshold, not simply a side effect of eating more.

How fat tissue itself grows: more cells or bigger cells#

A tissue can grow by making new cells (hyperplasia), by enlarging existing cells (hypertrophy), or both. Early work using the Coulter counter technique to size fat cells suggested that, as in laboratory rodents and humans, the number of fat cells in an animal was largely fixed early in life. Studies in cattle and sheep using similar cell-counting methods generally supported this, at least for subcutaneous and perirenal fat. Hood and Allen, for example, found hyperplasia complete in subcutaneous and perirenal fat of 14 month old steers at 470 kg, but still continuing in intramuscular fat. In crossbred wethers, hyperplasia in subcutaneous fat stopped by around 44 kg liveweight and 11 months of age, and periods of restricted feeding followed by re-feeding did not change subcutaneous fat cell numbers.

Other researchers, however, reported two distinct populations of cell sizes in the fat tissue of fat cattle, which would imply new cells forming even as animals fatten further. Thornton and Tume note that, using direct observation rather than the osmium-fixation Coulter counter method, their own data on sheep fat cell numbers, described further in the record on ovine adipose tissue cellularity, showed mostly single, normal distributions of cell size in perirenal, omental and subcutaneous fat from both thin and fat adult sheep. They argue the case for new fat cell formation in mature, fattening ruminants remains unresolved, and call for techniques beyond simple cell-size counting, such as labelled markers of cell division, to settle the question properly.

Which fuels ruminant fat cells actually burn#

In most fattening animals, including humans and birds, the liver is a major site of fat synthesis; in ruminants eating roughage, that role shifts almost entirely to adipose tissue itself. Hanson and Ballard's classical work showed that acetate, not glucose, is the dominant building block for fat synthesis in roughage-fed ruminant adipose tissue, because very little dietary glucose reaches the small intestine once rumen fermentation has done its work. Most of the body's glucose comes instead from the liver converting propionate, amino acids, glycerol and lactate into glucose.

Infusing glucose directly into the gut or bloodstream of sheep increased the use of glucose for fat synthesis twenty to forty times over, showing the system can adapt quickly when more glucose becomes available, as happens on grain-based diets. A side body of research proposed that the supply of NADPH, a cofactor needed for fat synthesis, might itself limit how much acetate can be converted to fat, forcing surplus acetate to be burned off as heat. Thornton and Tume argue the enzyme and substrate-flux evidence does not support this: in their reading, the capacity to generate NADPH is flexible enough to meet demand, so NADPH supply is more a consequence of high lipogenesis than a cause of it.

Species differences revealed by comparing sheep and cattle directly#

Much of the earlier argument over which enzyme limits fat synthesis assumed sheep and cattle adipose tissue behaved alike. Smith and Prior's side-by-side study of subcutaneous fat slices from steers and wethers on the same diet overturned that assumption. Acetyl unit incorporation into fat was far higher in sheep tissue than in cattle tissue (220 versus 45 nmol per minute per gram), and while acetate supplied about 80% of acetyl units in both species, cattle tissue drew relatively more on lactate and less on glucose than sheep tissue did. Adding acetate to the incubation medium boosted glucose use in sheep tissue but had no such effect in cattle tissue. In both species the pentose cycle supplied roughly half to two-thirds of the NADPH needed, but the enzyme that appeared to limit lipogenesis differed: acetyl-CoA carboxylase in sheep, fatty acid synthetase in cattle.

A further comparison by Smith and Crouse found that different fat depots within the same animal behave quite differently again. Intramuscular fat relied far more on glucose than on acetate, while subcutaneous fat drew mostly on acetate, and intramuscular tissue overall had much lower rates of fat synthesis than subcutaneous tissue. Thornton and Tume read this as a sign that depot-specific differences in substrate preference might eventually be exploited to shift fat deposition away from carcase fat and toward, or away from, marbling fat, a theme also explored in the summary on stearic acid and marbling fat colour.

Does insulin control fat deposition in ruminants#

Insulin is the classic driver of fat storage in non-ruminants, but the review presents ruminants as something of an exception. In Hereford and Friesian steers, insulin response to tolbutamide treatment did not correlate with body fat percentage within or across breeds. Using alloxan-diabetic cattle, insulin injections and glucose infusions, Gregory and colleagues and Smith and colleagues concluded insulin has only a limited effect on fat-building and fat-mobilising processes in cattle.

Results in sheep were more mixed. One study found that infusing insulin into early-weaned lambs reduced the percentage of fat in the empty body, while another found that raising circulating insulin increased the rate of backfat synthesis in lambs, in the latter case using a euglycaemic insulin clamp that lifted plasma insulin from 13.5 to 160 mu/ml and doubled both glucose turnover and the conversion of glucose to glyceride glycerol. When Thornton and colleagues tested isolated sheep fat cells directly, insulin concentrations up to 1000 uU/ml had no effect on fat synthesis or breakdown, even though the same cells responded strongly to adrenaline, and rat fat cells studied under identical conditions did respond to insulin as expected. Later work by Etherton and Evock, by contrast, found insulin did stimulate fat synthesis in isolated bovine fat cells, with the effect depending on which source of bovine serum albumin was used in the culture medium, which Thornton and Tume flag as a reason to treat the insulin question as still open rather than settled.

Mobilising fat: hormones, beta-agonists and lipoprotein lipase#

Fat breakdown (lipolysis) in ruminant adipose tissue runs through the hormone-sensitive lipase system and is triggered by catecholamines, though ruminant tissue responds less strongly to adrenalin than laboratory animal tissue does. The review highlights beta-adrenergic agonists such as clenbuterol and cimaterol as a practical lever: in weaners fed in pens and in lambs grazing alongside their mothers, less than 100 micrograms of clenbuterol per head reduced carcase fat content and increased lean by some 30%, prompting the authors to describe such compounds as repartitioning agents. Isolated sheep fat cells treated with these agonists showed increased lipolysis and reduced fat synthesis, and treated sheep showed higher circulating free fatty acids. Treated sheep given clenbuterol at 5 micrograms per kilogram liveweight per day also showed higher circulating growth hormone (5.1 versus 4.0 ng/ml) and lower insulin (2.1 versus 1.4 ng/ml) than controls, suggesting the agonist's effect may work partly through these other hormones as well as directly on fat cells.

Growth hormone's own role was harder to pin down. Although raised growth hormone is linked to increased fat mobilisation in lactating cows, ovine growth hormone, along with thyroid-stimulating hormone, luteinising hormone and adrenocorticotrophic hormone, did not stimulate lipolysis in isolated sheep fat cells at concentrations up to 1000 ng/ml. The authors note that discrepancies between whole-animal and isolated-cell results mean growth hormone cannot be confidently ruled out as having a role in fat breakdown, since separate studies using both natural and laboratory-produced growth hormone found it lowered the amount of fat carried by sheep.

Lipoprotein lipase and early attempts at immunological control#

Lipoprotein lipase (LPL) sits on the inner surface of capillary walls and controls how triglyceride-rich fat particles are pulled out of the blood and into tissue, directing them toward muscle for fuel or toward adipose tissue for storage depending on which tissue is making the enzyme at the time. Because LPL has a very short half-life, its activity at any moment reflects how much is currently being made; in a fasting animal, adipose tissue stops making it while muscle keeps going. Thornton and Tume report that ovine LPL has a low Km (apparent) for triglyceride of 0.4 mM, well below the figure of around 5 mM measured for rat fat tissue LPL, meaning the sheep enzyme can clear fat from blood even at low triglyceride concentrations. They also isolated two distinct activator proteins for LPL from sheep plasma, of similar size to each other, each as effective as human apolipoprotein CII at activating the enzyme.

The review then describes early attempts to manipulate fat deposition immunologically, a different strategy to the metabolic and hormonal approaches described earlier. Injecting rats with antiserum raised in sheep against rat fat cell membranes produced a substantial breakdown of fat cells and a 30% reduction in carcase fat content, with corresponding increases in protein and water content. When Thornton and Tume attempted a similar approach in lambs, using horse antiserum raised against sheep fat cell membranes, they found no change in LPL activity, plasma triglyceride, or carcase fat composition, although treated lambs did show a rise in plasma lactate dehydrogenase, a sign of some cell damage. They suggest the shorter trial period and the larger size of lambs compared with the rats used in the original experiments may explain the lack of effect, leaving this approach, in our reading, as a promising but still unproven line of attack given it worked once in rats but failed to reproduce in a ruminant species under different conditions.

Sources and further reading#

• Trove library search: find a library that holds the paper
• Meat & Livestock Australia: red meat industry research and marketing body
• CSIRO research: Australia's national science agency

Questions#

— The Livestock Library team