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Cow's milk polar lipids reduce atherogenic lipoprotein cholesterol,modulate gut microbiota and attenuate atherosclerosis development in LDL-receptor knockout mice fed a Western-type diet
Affiliation:1. Department of Biological Sciences, University of Limerick, Co. Limerick, Ireland;2. Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland;3. Alimentary Pharmabiotic Centre, University College Cork, Co. Cork, Ireland;1. Department of Biological Sciences, University of Limerick, Limerick, Ireland;2. Health Research Institute (HRI), University of Limerick, Limerick, Ireland;3. Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland;4. APC Microbiome Ireland, Cork, Ireland;5. Department of Life and Environmental Sciences, University of Cagliari, via Ospedale 72, 09124 Cagliari, Italy;1. Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing, China;2. College of Food Science & Nutritional Engineering, Key Laboratory of Functional Dairy, Ministry of Education, China Agricultural University, Beijing, China;3. Department of Animal Sciences, Washington State University, Pullman, WA, USA;1. Friedrich Schiller University of Jena, Department of Nutritional Physiology, Dornburger Straße 24, D-07743 Jena, Germany;2. University Hospital of the Friedrich Schiller University of Jena, Department of Dermatology, Erfurter Straße 35, D-07740 Jena, Germany;3. University Hospital of the Friedrich Schiller University of Jena, Institute of Clinical Chemistry and Laboratory Medicine, Erlanger Allee 101, D-07747 Jena, Germany;4. SRH Wald-Klinikum Gera, Department of Dermatology and Allergology, Straße des Friedens 122, D-07548 Gera, Germany
Abstract:Milk sphingomyelin (SM), a polar lipid (PL) component of milk fat globule membranes, is protective against dyslipidemia. However, it is unclear whether ingestion of milk PLs protect against atherosclerosis. To determine this, male LDLr−/− mice (age 6 weeks) were fed ad libitum either a high-fat, added-cholesterol diet (CTL; 45% kcal from fat, 0.2% cholesterol by weight; n=15) or the same diet supplemented with 1% milk PL (1% MPL; n=15) or 2% milk PL (2% MPL; n=15) added by weight from butter serum. After 14 weeks on diets, mice fed 2% MPL had significantly lower serum cholesterol (−51%) compared to CTL (P<.01), with dose-dependent effects in lowering VLDL- and LDL-cholesterol. Mice fed 2% MPL displayed lower inflammatory markers in the serum, liver, adipose and aorta. Notably, milk PLs reduced atherosclerosis development in both the thoracic aorta and the aortic root, with 2% MPL-fed mice having significantly lower neutral lipid plaque size by 59% (P<.01) and 71% (P<.02) compared to CTL, respectively. Additionally, the 2% MPL-fed mice had greater relative abundance of Bacteroidetes, Actinobacteria and Bifidobacterium, and lower Firmicutes in cecal feces compared to CTL. Milk PL feeding resulted in significantly different microbial communities as demonstrated by altered beta diversity indices. In summary, 2% MPL strongly reduced atherogenic lipoprotein cholesterol, modulated gut microbiota, lowered inflammation and attenuated atherosclerosis development. Thus, milk PL content may be important to consider when choosing dairy products as foods for cardiovascular disease prevention.
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