Releases Archive 2007

Leptin was discovered in 1994 through its absence from a long-established mutant laboratory mouse - the obese mouse - that eats voraciously, deposits a lot of fat and grows to three or more times ‘normal’ weight. When injected with leptin, obese mice eat less and lose weight making leptin an obvious candidate for treating obesity in man. However, worldwide, only a very small number of morbidly obese people have been found that are genetically aleptinaemic. While injecting leptin into these very rare individuals does indeed lower their appetite and cause dramatic weight loss, most ‘normally’ obese humans produce plenty of leptin and do not respond to injection with more.

For livestock producers, the association of leptin with fat has a quite different significance and this article explains what an animal’s leptin status tells us and how we might be able to use this in a practical way. We will also see how technical innovations shifted research interest away from leptin protein to the leptin gene, and the new opportunities this has created.

Leptin is produced mainly by adipose cells so that, logically, leptin concentrations in blood are usually higher in fatter animals. The photograph shows a comparison between a very fat sheep (with high leptin) and a very thin one (low leptin). In fact, the blood leptin level measured at or near slaughter is a quite good indicator of the amount of fat in cattle, sheep and pigs, making leptin a potential marker for carcase evaluation. Figure 1 shows just how well leptin in sheep was related to the amount of fat in the carcase in one local study.

Fat accumulates in many parts of the animal body with major subcutaneous and visceral deposits as well as the intermuscular and intramuscular fats (marbling) which, in meat animals, are especially important for cooking and eating quality (texture and flavour). Consumer attitudes to marbling are mixed. Some find it desirable while others prefer visibly lean meat but, in Japan and the United States of America, the most expensive ‘melt-in-the-mouth’ beef is from highly-marbled Wagyu cattle. In the United Kingdom, highly marbled beef from our more traditional cattle might also attract a premium and, if so, early selection of the most appropriate animals will be important. But leptin levels in young stock do not reliably predict how fat or how marbled they will eventually become and are of little use as an early selection aid in a breeding programme. However, the leptin gene is a potential candidate for this purpose and we will look at this aspect a little later.

Another characteristic of the obese mouse strain that started the leptin story is that such mice are infertile. Obese mice don’t pass through puberty and cannot reproduce, but leptin injections restore their fertility. With the link between leptin and fat stores, this suggests that leptin might be a signal to the brain that there is enough energy stored as body fat to support a pregnancy, so that hormonal and physiological preparations for reproduction can proceed. Female endurance athletes often have very low body mass with little body fat and suffer from infertility during much of their competitive career and for sometime thereafter. Typically, such women also have very low leptin levels and injecting leptin has helped restore many to a fertile reproductive state.

There is a clear parallel between these athletes and the poor body condition and rising infertility of dairy cows – particularly, high genetic merit cows.  By all conventional measures (days to first heat, days to first service, calving interval) the fertility of many herds has fallen steadily in Northern Ireland and elsewhere for over twenty years, creating costly management problems. Worsening fertility in high genetic merit cows has been linked to the degree and duration of the negative energy balance that they suffer in the first few weeks of lactation. Research at AFBI Hillsborough has calculated herd average energy balance values as low as –60 MJ per day per cow in the first few weeks after calving. Cows try to meet this energy shortfall from their fat and muscle reserves. Leptin levels and those of another hormone, IGF-1 (insulin like growth factor 1) are both very low at this time and may be linked to the delayed return of cyclicity.  Leptin is implicated in regulating the pulsatility of luteinising hormone secretion whilst IGF-1 is implicated in follicle development, so that higher blood levels of leptin or IGF-1 might both help in the post-partum return to fertility. Levels of both hormones are affected by nutrition, suggesting that changes to the diet before and after calving might be a way to optimise the levels of these hormones.   

Turning to the technical innovations mentioned earlier, crop and livestock farmers already benefit from many of the advances in biological discovery over the last ten to twenty years. One of the most significant is the use of genetic markers for quality traits (‘marker assisted selection’) that involves identifying genes that determine the visible and not-so-visible production characteristics and carry the genetic blueprint to manufacture the tools (enzymes and other proteins) that help to create the characteristics. For livestock farmers, the most important genes are those associated with feed intake and feed conversion efficiency, growth rate, body composition (fat versus lean), milk yield and milk composition, prolificacy and reproductive success. Farmers have selected for such traits for centuries using both the direct measures and visible aids such as coat colour, but technology now allows us to use markers more closely tied to the genes.

Genes suffer mutations over time. Large mutations usually result in a protein that is incapable of doing the job it is intended to do but the smallest change (a single nucleotide polymorphism or SNP) results in two similar versions of the protein, both of them active, but one more effective than the other. For SNPs linked to a quality trait, the degree to which the trait is displayed in an individual animal depends on which of the two SNP variants it carries. This is more easily explained through the example of the well-researched leptin SNP. The normal role for leptin is to reduce feed intake, so an animal with normal leptin is likely to eat less than one carrying the leptin variant and will thus have less energy available above maintenance for production. In this way, the leptin SNP can partly determine the amount of fat a meat animal might deposit or the amount of milk a cow might yield (within a 2–3 kg range). The SNP variant carried by any animal can be quickly identified by DNA analysis helping a farmer decide if, and how best, to use that animal to meet his breeding objectives.

Farmers can already purchase SNP tests for leptin and other proteins linked to marbling score, tenderness, milk yield and feed conversion efficiency. However, it is important to understand that SNP test results do not guarantee a specific level of production in any individual animal. Instead, they show the production potential that would be expected of a high percentage of animals with that same SNP under optimal management. This allows a farmer to select the animals best suited to his breeding objectives or to separate younger stock into groups to arrive at slaughter weight in similar condition and at more or less the same time, when fed appropriately. But to have even a chance of achieving the potential suggested by the test, it is important that all other inputs such as feed quantity and quality, handling stress and disease protection are also optimised.

In the future, other SNP tests might prove useful for the prediction of fertility or disease resistance – features that will become increasingly important and valuable to producers. Exciting as they are, such technological advances add to, rather than replace the need for sound management practices when seeking to improve performance or fertility.