title: Dietary sphingomyelin lowers hepatic lipid levels and inhibits intestinal cholesterol absorption in high-fat-fed mice.
abstract: Controlling intestinal lipid absorption is an important strategy for maintaining lipid homeostasis. Accumulation of lipids in the liver is a major risk factor for metabolic syndrome and nonalcoholic fatty liver disease. It is well-known that sphingomyelin (SM) can inhibit intestinal cholesterol absorption. It is, however, unclear if dietary SM also lowers liver lipid levels. In the present study (i) the effect of pure dietary egg SM on hepatic lipid metabolism and intestinal cholesterol absorption was measured with [(14)C]cholesterol and [(3)H]sitostanol in male C57BL/6 mice fed a high-fat (HF) diet with or without 0.6% wt/wt SM for 18 days; and (ii) hepatic lipid levels and gene expression were determined in mice given a HF diet with or without egg SM (0.3, 0.6 or 1.2% wt/wt) for 4 weeks. Mice supplemented with SM (0.6% wt/wt) had significantly increased fecal lipid and cholesterol output and reduced hepatic [(14)C]cholesterol levels after 18 days. Relative to HF-fed mice, SM-supplemented HF-fed mice had significantly lower intestinal cholesterol absorption (-30%). Liver weight was significantly lower in the 1.2% wt/wt SM-supplemented mice (-18%). Total liver lipid (mg/organ) was significantly reduced in the SM-supplemented mice (-33% and -40% in 0.6% wt/wt and 1.2% wt/wt SM, respectively), as were triglyceride and cholesterol levels. The reduction in liver triglycerides was due to inactivation of the LXR-SREBP-1c pathway. In conclusion, dietary egg SM has pronounced hepatic lipid-lowering properties in mice maintained on an obesogenic diet.
authors: Nutrition and Metabolism Group, Heart Research Institute, Sydney, New South Wales, Australia.
authors: Rosanna W S
authors: RW
authors: Chung
authors: Alvin
authors: A
authors: Kamili
authors: Sally
authors: S
authors: Tandy
authors: Jacquelyn M
authors: JM
authors: Weir
authors: Raj
authors: R
authors: Gaire
authors: Gerard
authors: G
authors: Wong
authors: Peter J
authors: PJ
authors: Meikle
authors: Jeffrey S
authors: JS
authors: Cohn
authors: Kerry-Anne
authors: KA
authors: Rye
mesh_terms: D000818:Animals; D001835:Body Weight; D002784:Cholesterol / Q000378:metabolism*; D016000:Cluster Analysis; D059305:Diet, High-Fat; D019587:Dietary Supplements; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D007408:Intestinal Absorption / Q000187:drug effects*; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D009929:Organ Size; D013109:Sphingomyelins / Q000494:pharmacology*
chemical_list: D013109:Sphingomyelins; D002784:Cholesterol