Abstract
Scope: Milk from various species differs in nutrient composition. In particular, human milk (HM) and donkey milk (DM) are characterized by a relative high level of triacylglycerol enriched in palmitic acid in sn-2 position. These dietary fats seem to exert beneficial nutritional properties through N-acylethanolamine tissue modulation. The aim of this study is to compare the effects of cow milk (CM), DM, and HM on inflammation and glucose and lipid metabolism, focusing on mitochondrial function, efficiency, and dynamics in skeletal muscle, which is the major determinant of resting metabolic rate. Moreover, we also evaluated the levels of endocannabinoids and N-acylethanolamines in liver and skeletal muscle, since tissue fatty acid profiles can be modulated by nutrient intervention.Procedures: To this aim, rats were fed with CM, DM, or HM for 4 weeks. Then, glucose tolerance and insulin resistance were analyzed. Pro-inflammatory and anti-inflammatory cytokines were evaluated in serum and skeletal muscle. Skeletal muscle was also processed to estimate mitochondrial function, efficiency, and dynamics, oxidative stress, and antioxidant/detoxifying enzyme activities. Fatty acid profiles, endocannabinoids, and N-acylethanolamine congeners were determined in liver and skeletal muscle tissue.Results: We demonstrated that DM or HM administration reducing inflammation status, improves glucose disposal and insulin resistance and reduces lipid accumulation in skeletal muscle. Moreover, HM or DM administration increases redox status, and mitochondrial uncoupling, affecting mitochondrial dynamics in the skeletal muscle. Interestingly, HM and DM supplementation increase liver and muscle levels of the N-oleoylethanolamine (OEA), a key regulator of lipid metabolism and inflammation.Conclusions: HM and DM have a healthy nutritional effect, acting on inflammatory factors and glucose and lipid metabolism. This beneficial effect is associated to a modulation of mitochondrial function, efficiency, and dynamics and to an increase of OEA levels in skeletal muscle.
Highlights
Human milk (HM), the natural food of infants, provides an adequate supply of all nutrients necessary to support postnatal growth and development
IL 10 level increased in the serum of all treated groups (HM>donkey milk (DM)>cow milk (CM)) compared to control (Figure 1F), while IL 10 level increased in the skeletal muscle of DM and HM compared to control and CM group (Figure 1F inset)
Leptin concentration was significantly higher in CM-treated animals compared to the other groups; consistently, adiponectin concentration decreased in CM-fed animals, whereas it significantly increased in the DM- and HMtreated rat (Figures 1G,H)
Summary
Human milk (HM), the natural food of infants, provides an adequate supply of all nutrients necessary to support postnatal growth and development It provides immunomodulant components and plays a key role in preventing inflammation and metabolic diseases throughout life (Agostoni et al, 2013; Cacho and Lawrence, 2017). It has been demonstrated that breastfed individuals have lower rate of obesity and type 2 diabetes than those fed with infant formula (Owen et al, 2006) Such effects have been attributed to appetite regulation and reduced weight gain in breast-fed children and/or to the presence of unique nutrients or bioactive constituents in HM. PPARα activation increases peroxisomal and mitochondrial oxidation and leads to anti-inflammatory and antioxidant effects (Fu et al, 2005; Lo Verme et al, 2005; Contreras et al, 2013)
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