Nutrienti per la salute dell animale e miglioramento delle caratteristiche dietetiche dei prodotti di origine animale

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1 Nutrienti per la salute dell animale e miglioramento delle caratteristiche dietetiche dei prodotti di origine animale Giovanni Savoini Dipartimento di Scienze Veterinarie per la Salute, la Produzione Animale e la Sicurezza Alimentare Università degli Studi di Milano

2 Omega 3 fatty acids have a positive impact on human health

3 Feeding fish oil to dairy goats determined an increase of EPA and DHA content in milk fat, goats and kids plasma Plasma EPA e DHA content dairy goats (%) Apparent Transfer efficiency : 7.69% EPA, 8.00 % DHA EPA e DHA content milk fat (%) Control Fish oil Stearate EPA 0.01 b 0.26 a 0.01 b DHA Plasma EPA e DHA content kids (%) Control Fish oil Stearate EPA 0.26 b 0.96 a 0.47 DHA 1.16 b 2.28 a 1.70

4 Can fatty acids affect animal health? Some examples in dairy ruminants

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6 Insulin resistance All mammals develop some degree of insulin resistance during late pregnancy in order to direct nutrients towards the foetus and to lactation However, it appears that cows can also develop insulin resistance in body fat that is analogous to Type 2 diabetes in humans. As cows approach calving, the net result of this Type 2 diabetes-like condition is a rapid increase in circulating concentrations of nonesterified fatty acids (NEFA) and a rapid decrease in dry matter intake (DMI). This NEFA spike is related to nearly all energy-and immune-related metabolic disorders in transition cows, including displaced abomasum, ketosis,fatty liver, metritis and mastitis. Overton,.2007

7 Sub clinical ketosis BHBA > 1,20 mmol/l NEFA > 0,75 mmol/l When cows are in a situation of NEB (Negative Energy Balance), lipolysis increases to supply energy, and the plasma level of NEFA increases High level of plasma NEFA (> 0,75 mmol/l) engenders hepatic steatosis (fatty liver) because NEFA in the liver are transformed in tryglicerides, and the liver has a limited capacity to export fatty acids through the production of Very Low Density Lipoproteins (VLDL) Drackley et al., 2006 Fatty liver

8 Dietary fatty acids have been shown to modulate immune response, the most powerful being the ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and among them, those derived from fish oil, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

9 Sordillo et al., 2009

10 During the peripartum the concentration of palmitate (C16:0) and stearate (C18:0) in NEFA increases, while the concentration of fatty acids omega 3 decreases. Contreras et al. (2012) showed that the exposition of Bovine Aortic Endothelial Cells (BAEC) to a mixture of fatty acids that reflects the composition of NEFA during the first week of lactation (C14:0, 3%; C16:0, 30%; C18:0, 45%; cis C18:1n-9, 16%; C18:2n-6, 5%; DHA 1%), determined an increase of the gene expression of cytochines (IL-6, interleukin 6; IL-8, interleukin 8) and of adhesion molecules (ICAM1, Intercellular Adhesion Molecule; VCAM1,Vascular Adhesion Molecule 1) associatd to an increase of inflammatory response, of ROS, and of proinflammatory metabolites of linoleic acid,compared to cells not exposed to fatty acids.

11 Gene expression of IL-8 in BAEC exposed to different mixtures of fatty acids (Contreras et al., 2012)

12 Gene expression of VMCAM1 in BAEC exposed to different mixtures of fatty acids (Contreras et al., 2012)

13 Cameline, rich in n3 FA, increased insulin sensitivity index, which represents the net capacity for insulin to promote glucose disposal, both by diminishing endogenous glucose production and by increasing glucose utilization Insulin sensitivity index Control Tallow Cameline 1,03 0,73 1,39 Salin et al, 2012

14 During peripartum immune function is suppressed Linfocytes Neutropils (Goff and Horst, 1997)

15 The node color intensity indicates the expression of genes: red upregulated, green downregulated in severe negative energy balance (SNEB) vs. mild negative energy balance (MNEB) spleen The increased expression of antioxidant genes and genes involved in free radical scavenging in animals in severe negative energy balance (SNEB)compared to animals in mild negative energy balance (MNEB), is likely a response to mitigate the damaging effects of increased concentrations of ROS (Morris et al., 2009)

16 High level of NEFA has a negative impact on the immune response LLacetera et al., 2004

17 Agazzi et al., 2004

18 Administration of fish oil may modulate immunosuppression during the transition period in the goat with a constant increase in CD4- and CD8- positive leukocytes in the blood Absolute values cell subset Days post kidding Palm oil (47 g d) Fish oil (47 g d) CD4 positive cells Kidding 1, a 1, DIM 2, b 2, DIM 1, b 2, CD8 positive cells Kidding a 4 DIM 1, b 15 DIM , b Goats fed fish oil had intramammary infections (CNS) without an increase in SCC and with relative stable levels of leukocites, this could be reasonably explained by the anti-inflammatory effects of fish oil. Bronzo et al.., 2010

19 Neutrophils and monocytes are essential components of the innate immune response and major contributors to inflammatory response against bacteria and fungi. They fulfill their role by phagocytizing pathogens and exposing them to the destructive action of molecules including, among the other, Reactive Oxygen Species-ROS.

20 EPA and DHA may improve the defensive performance of goat s neutrophils against bacteria by increasing their phagocytosis activity Pisani et al., 2009

21 EPA and DHA may improve the defensive performance of goat s monocytes against bacteria by increasing their phagocytic activity Lecchi et al., 2012

22 High concentration of EPA and DHA induces lipid droplets formation in caprine monocytes Lecchi et al., 2013 EPA and DHA may modulate lipid droplets formation by regulatimg PLIN2 and PLIN3 mrna expression. This activity can have a profound impact on monocyte immune functions, since a relationship between perilipin expression and innate immunity reactions has been recently demonstrated.

23 Omega 3 fatty acids improve fertility in dairy cows

24 Cows fed n3 (fish oil) breeding diets showed improved ferility Santos et al., 2013

25 Santos et al., 2013

26 Omega-6 transition period Omega DIM Silvestre et al., 2011

27 Dams dietary intake affects offspring milk performance and immunity

28 Milk yield of Holstein heifers born from dams fed prepartum diets containing no supplemental fat (control), saturated fatty acids (SFA) and Ca salts containing essential fatty acids (EFA) and fed milk replacer with low (LLA) or high (HLA) concentrations of linoleic acid dams Control SFA (C16:0,C18:0) EFA (C18:2, C18:3) heifers LLA HLA LLA HLA LLA HLLA d ME milk, kg P LLA=0,175 g of linoleic acid/bw 0,75 HLA=0,562 g of linoleic acid/bw 0,75 P= SFA+EFA vs control prepartum Santos et al., 2013

29 Serum total IgG, as percentage of serum total protein (ST IgG,% of STP) of Holstein calves born from dams fed diets supplemented with no fat (control), saturated fatty acids (SFA), or essential fatty acids (EFA) during late gestation dams Control SFA (C16:0,C18:0) ST IgG, % of TSP EFA (C18:2, C18:3) prim plur prim plur prim plur 37,5 35,2 42,3 44,6 39,1 37, P P= SFA+EFA vs control prepartum Santos et al., 2013

30 Cytokine production from colon Mice born from breeders fed low fat (LF) or fish oil (n3)diets Cytokine production from spleen Myles et al., 2014

31 Conclusion n3 fatty acids can modulate immune and inflammatory response There are some evidences of a role of fatty acids enriched diet fed do dams also on offspring.