Milk polar lipids modulate lipid metabolism, gut permeability, and systemic inflammation in high-fat-fed C57BL/6J ob/ob mice, a model of severe obesity

Abstract

Dynamic interactions between lipid metabolism, gut permeability, and systemic inflammation remain unclear in the context of obesity. Milk polar lipids, lipids derived from the milk fat globule membrane, could positively affect the aforementioned obesity-related endpoints. This study aimed to test the hypotheses that milk polar lipids will reduce gut permeability, systemic inflammation, and liver lipid levels, and differentially affect the hepatic expression of genes associated with fatty acid synthesis and cholesterol regulation in preexisting obesity. We fed 3 groups of C57BL/6J ob/ob mice (n = 6 per group) for 2 wk: (1) a modified AIN-93G diet (CO) with 34% fat by energy; (2) CO with milk gangliosides (GG) at 0.2 g/kg of diet; and (3) CO with milk phospholipids (PL) at 10 g/kg of diet. The GG and PL were provided as semi-purified concentrates and replaced 2.0% and 7.2% of dietary fat by energy. The GG and PL did not affect total food intake, weight gain, fasting glucose, or gut permeability. The PL decreased liver mass and the mesenteric fat depot compared with the CO. The GG increased tight junction protein occludin in colon mucosa compared with the CO. The GG and PL decreased tight junction protein zonula occludens-1 in jejunum mucosa compared with the CO. Plasma endotoxin increased during the study but was unaffected by the treatments. Compared with the CO and GG, the PL increased plasma sphingomyelin and plasma IL-6. The GG and PL differentially regulated genes associated with lipid metabolism in the liver compared with the CO. Regarding general effects on lipid metabolism, the GG and PL decreased lipid levels in the liver and the mesenteric depot, and increased lipid levels in the plasma. Diet consumption decreased significantly when the ob/ob mice were kept in metabolic cages, which were not big enough and resulted in unwanted animal deaths. Future studies may keep this in mind and use better metabolic equipment for ob/ob mice. In conclusion, dietary milk polar lipids may have limited beneficial effects on gut barrier integrity, systemic inflammation, and lipid metabolism in the context of severe obesity.

Keywords: gut permeability; inflammation; lipid metabolism; milk polar lipids.