The purpose of lactation is for nutrient provision and also importantly for protection from various environmental stressors. Milk polar lipids reduce cholesterol, protect against bacterial infection, reduce inflammation and help maintain gut integrity. Dynamic interactions within dietary fat, lipid metabolism, gut permeability and inflammatory cytokines remain unclear in the context of obesity and systemic inflammation. A rat model and three mouse models were developed to test the hypotheses that dietary milk polar lipids may affect lipid metabolism and intestinal integrity and may protect against systemic inflammation in the context of stressful diet, systemic inflammation, and obesity. The milk polar lipids isolates had complex effects on lipid metabolism and associated gene expression in the rat model. There were complex dynamics in lipid metabolism, gut permeability and systemic inflammation at different time points in all mouse models. The milk phospholipids increased gut permeability in genetic and diet-induced obesity and during the lipopolysaccharide (LPS) -induced inflammation. The phospholipids increased the plasma LPS level in genetic obesity and during the LPS stress. The phospholipids reduced liver mass and liver lipids in genetic obesity and during the LPS-induced inflammation. The phospholipids increased the body fat in the diet-induced obesity model. The milk gangliosides did not significantly affect gut permeability, systemic inflammation, and lipid metabolism in all three mouse models. Current estimate by the Centers for Disease Control is that about 1/3 Americans are obese (body mass index, BMI ≥ 30) and 1/3 Americans are overweight (25 ≤ BMI < 30). More than 25% of Americans today have a fatty liver which could lead to further health problems. The data from this dissertation shed light on the complicated interrelationships between gut permeability, systemic inflammation, and lipid metabolism in obesity. The results contribute to our understanding of the bioactivities of milk polar lipids and provide scientific evidence for the role of milk polar lipids rich materials in affecting biological functions. The study of the influence of milk polar lipids on gut barrier integrity adds new information on understanding the mechanisms of gut leakiness and recovery. The investigation of the impact of milk polar lipids on lipid metabolism reveals new perspectives for the development of diet-induced obesity.

The purpose of lactation is for nutrient provision and also importantly for protection from various environmental stressors. Milk polar lipids reduce cholesterol, protect against bacterial infection, reduce inflammation and help maintain gut integrity. Dynamic interactions within dietary fat, lipid metabolism, gut permeability and inflammatory cytokines remain unclear in the context of obesity and systemic inflammation. A rat model and three mouse models were developed to test the hypotheses that dietary milk polar lipids may affect lipid metabolism and intestinal integrity and may protect against systemic inflammation in the context of stressful diet, systemic inflammation, and obesity. The milk polar lipids isolates had complex effects on lipid metabolism and associated gene expression in the rat model. There were complex dynamics in lipid metabolism, gut permeability and systemic inflammation at different time points in all mouse models. The milk phospholipids increased gut permeability in genetic and diet-induced obesity and during the lipopolysaccharide (LPS) -induced inflammation. The phospholipids increased the plasma LPS level in genetic obesity and during the LPS stress. The phospholipids reduced liver mass and liver lipids in genetic obesity and during the LPS-induced inflammation. The phospholipids increased the body fat in the diet-induced obesity model. The milk gangliosides did not significantly affect gut permeability, systemic inflammation, and lipid metabolism in all three mouse models. Current estimate by the Centers for Disease Control is that about 1/3 Americans are obese (body mass index, BMI ≥ 30) and 1/3 Americans are overweight (25 ≤ BMI < 30). More than 25% of Americans today have a fatty liver which could lead to further health problems. The data from this dissertation shed light on the complicated interrelationships between gut permeability, systemic inflammation, and lipid metabolism in obesity. The results contribute to our understanding of the bioactivities of milk polar lipids and provide scientific evidence for the role of milk polar lipids rich materials in affecting biological functions. The study of the influence of milk polar lipids on gut barrier integrity adds new information on understanding the mechanisms of gut leakiness and recovery. The investigation of the impact of milk polar lipids on lipid metabolism reveals new perspectives for the development of diet-induced obesity.

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