Dietary Milk Sphingomyelin Reduces Systemic Inflammation in Diet-Induced Obese Mice and Inhibits LPS Activity in Macrophages

Abstract

High-fat diets (HFD) increase lipopolysaccharide (LPS) activity in the blood and may contribute to systemic inflammation with obesity. We hypothesized that dietary milk sphingomyelin (SM), which reduces lipid absorption and colitis in mice, would reduce inflammation and be mediated through effects on gut health and LPS activity. C57BL/6J mice were fed high-fat, high-cholesterol diets (HFD, n = 14) or the same diets with milk SM (HFD-MSM, 0.1% by weight, n = 14) for 10 weeks. HFD-MSM significantly reduced serum inflammatory markers and tended to lower serum LPS (p = 0.08) compared to HFD. Gene expression related to gut barrier function and macrophage inflammation were largely unchanged in colon and mesenteric adipose tissues. Cecal gut microbiota composition showed greater abundance of Acetatifactor genus in mice fed milk SM, but minimal changes in other taxa. Milk SM significantly attenuated the effect of LPS on pro-inflammatory gene expression in RAW264.7 macrophages. Milk SM lost its effects when hydrolysis was blocked, while long-chain ceramides and sphingosine, but not dihydroceramides, were anti-inflammatory. Our data suggest that dietary milk SM may be effective in reducing systemic inflammation through inhibition of LPS activity and that hydrolytic products of milk SM are important for these effects.

Milk Polar Lipids: Underappreciated Lipids with Emerging Health Benefits

“…While health effects of PLs from eggs [7] and SLs [8] have been reviewed previously, the health effects of consuming milk polar lipids have not been reviewed extensively. Since the SLs found within MFGM are known to impact various aspects of lipid metabolism [9,10], gut microbiota [10], and inflammation [9,11], milk polar lipids may be considered as food matrix factors that may confer health benefits and/or impact effects of other dietary lipids, with implications for full-fat vs. lower-fat dairy varieties. This review summarizes the recent basic science and clinical research examining food sources and health effects of milk polar lipids, as well as to identify gaps in the scientific literature related to milk polar lipids research.…”

Milk Polar Lipids in a High‐Fat Diet Can Prevent Body Weight Gain: Modulated Abundance of Gut Bacteria in Relation with Fecal Loss of Specific Fatty Acids

“…Both high‐fat fed and ob/ob mice have been associated with a metabolic endotoxemia, dependent on the translocation of LPS notably due to intestinal permeability, that can induce inflammation in target organs, namely adipose tissue and liver . Previous studies in mice fed semi‐synthetic HF diets (based on starch and casein, 40–60%kJ as fat) reported that addition of milk‐SM or MPL decreased HF‐induced inflammation, notably in EAT . Here, the chow‐based HF diet treatment itself did not induce inflammation, probably again as it was more balanced and lipids were not composed of palm oil only.…”

“…After 10 weeks of a synthetic HF diet supplemented with 0.1% of milk‐SM (60% kcal from fat, 0.15% cholesterol), Norris et al. observed no differences of body weight gain in mice; while another synthetic diet for only 4 weeks (45% kcal from fat) resulted in lower body weight gain when including SM . We previously observed no significant difference in body weight gain and adiposity when 1.2% MPL was incorporated in a palm‐oil‐based synthetic HF diet after 8 weeks with an isolipidic design .…”

“…Norris et al. have shown that mice fed with a HF diet with milk‐SM had lower endotoxemia compared to control HF diet . In this context, we must highlight that the intestine is permanently colonized by a rich community of microorganisms, the intestinal microbiota, and in the absence of hypoxia or chemically or heat‐induced stressors, a “healthy” microbiota is one component of a proper intestinal barrier.…”

Milk: Bioactive Components and Role in Human Nutrition

“…Then, Gambelli [8] provides an updated picture of methodologies for the assessment of lactose. Some studies on the potential benefits of some milk components [9,10], as well as a consideration from a nutritional point of view of organic vs. conventional milk with regard to fat-soluble vitamins and iodine content [11], are also discussed.…”