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This latter result in an increase in reproduction and health problems (Berry and Crowley, 2013), which will increase the rate of dairy female culling, and finally it will decrease the animal lifespan with a detrimental effect on lifetime feed efficiency. The impact of extending duration of lifespan on the  reduction of  the cost of nonproductive phase (growth of heifers) and increase the long-term feed efficiency remains to be quantified (Puillet et al. 2016). Characterizing and quantifying the metabolic determinants of long-term efficiency remain a challenge to develop tools to improve and to model long-term efficiency. 

Long-term feed efficiency reflects the interaction between the coordinated regulations of nutrient allocation (homeorhesis) to different life functions (lactation, reproduction…) at each given lactation period and the management of repeated periods of nutrient shortage and excess (homeostasis) during the animal lifespan. Specific phases of energy shortage are characterized during pre-and post-partum periods that may lead to nutritional disorders as ketosis and fatty liver (Grummer 2008), which show specifically the role of adipose tissue and of liver functions. Despite the great improvements of knowledge dealing with adipose tissue metabolism and more globally with fluxes of energy-providing nutrients (Contreras et al., 2018), it is far from clear how the dynamic management of body reserves (deposition/repletion) especially during the strategic phases of lactation may be a determinant of lifespan. 

Proposed research questions and associated strategy. We propose to phenotype the individual variability of lactating goats for their allocation efficiency of energy-yielding nutrients during their whole lifespan. We also intend to use genetic lines divergent for the longevity in goats (Longevity+ vs Longevity –, Palhière et al., 2018), in order to evaluate the contribution of that genetic component to feed efficiency. This will help to understand the relationships between short-term and long-term feed efficiency, with a specific focus on energy fluxes within the body in order to provide biomarkers and tools to optimize the individual management of body reserves along the lifespan, and to detect and prevent nutritional disorders. Moreover, in relation with the resource acquisition sublevel, we will quantify the interaction between resources acquisition and resources allocation, and the changes in adaptive capacity of animals to nutritional challenges over time. The 2 combined approaches of phenotyping and genetics divergent lines, will implicate to realize long term follow-up of energetic biomarkers in different matrixes (milk, blood, and urine), and to quantify energetic fluxes within the body during periods of energy shortage/repletion by the use of stable isotopes analytical methods (Deuterium to predict changes in lipid body composition, C13 to possibly estimate lipogenesis). This will be associated to the characterization of animal responses to short term nutritional challenges (feed restriction, overfeeding) at different levels of the animal organization, to quantify the main mechanisms of metabolic robustness.

We also intend to identify biomarkers responsible for early modifications in metabolic fingerprints/profiles of animals caused by these challenges (and thus applicable to naturally-occurring challenges during animal lifespan). Association between classical biochemical analyses, powerful analytical tools (1H Nuclear Magnetic Resonance spectroscopy, mass spectroscopy) in the above described matrixes and adequate statistical and mathematical analyses will enable to identify potential biomarkers to predict the risk of nutritional disorders at very early stages.

Because integrating the coordinated functioning of all metabolic levels during the lifespan is complex, a systemic modelling approach will provide an optimal frame to integrate experimental results into predictive models of long-term feed efficiency and robustness. Associated with experimental works, we will particularly have the ambition to elaborate a generic multi-level model of animal efficiency. This model will make the links between the model of acquisition proposed above and the different metabolic models previously developed on the metabolic regulations and the resulting partition of nutrients within the lactation, on the priorities and trade off among productive and nonproductive functions during the lifespan, on the improvement of fertility, and on the contribution of resources acquisition and allocation to feed efficiency. A further challenge will also consist to integrate data from lower levels of organization (models of organ function, e.g. liver, adipose tissues) and possibly data from genomics (Loor et al., 2013). Ultimately, this final global model will allow a quantification of the relative importance of the core metabolic pathways dealing with energy fluxes use and efficiency and their alterations by genetics and nutrition.