Dietary Sphingomyelin Attenuates the Inflammatory Effects of an Obesogenic Diet in C57BL/6 Mice

Abstract

Obesity is associated with chronic low‐grade inflammation, characterized by long‐term activation of the innate immune system in a variety of metabolic tissues. Chronic low‐grade inflammation contributes to metabolic dysfunction, driving the associated health consequences of obesity. In rodent models, high fat diet‐induced obesity has been shown to promote inflammation in the distal intestinal tract and surrounding mesenteric adipose tissue. This localized inflammatory response of the intestinal tissues is thought to precede the systemic inflammation and insulin resistance seen with obesity. Finding dietary components that potentially ameliorate intestinal and mesenteric adipose inflammation may attenuate some detrimental effects of obesity. Sphingomyelin (SM) is a common dietary sphingolipid that is consumed predominantly from milk and eggs. Structurally diverse sphingolipids from various sources have shown anti‐inflammatory effects in multiple in vitro and in vivo models. In the current study, C57BL/6J mice (N = 52) were divided into 4 diet groups and fed for 10 weeks either a low fat control diet (10% kcal from fat) (LFD, n = 10), an obesogenic high fat, high cholesterol diet (60% kcal as fat, 0.15% added cholesterol) (HFD, n = 14), or the HFD supplemented with either 0.1% (w/w) egg‐derived SM (HFESM, n = 14) or bovine milk‐derived SM (HFMSM, n = 14). The mice were subsequently analyzed for circulating inflammatory cytokines, mesenteric adipose mRNA and colon mRNA. HFMSM significantly reduced several inflammatory cytokines in serum (IFNγ, IL‐6, TNFα and CCL2), while HFESM reduced circulating CCL2. HFMSM showed lower mRNA expression of macrophage markers in the colon (F4/80, CD68, and CD11c) and increased Glut4 expression in the mesenteric adipose. HFESM reduced markers of macrophages infiltration (CD68 and F4/80) and increased AdipoQ expression in the mesenteric adipose. In summary, this data suggests that dietary SM can partly attenuate obesity‐related inflammation and modulate macrophage markers in the colon and mesenteric adipose in high fat diet‐induced obese mice. More research is warranted to determine if the structurally distinct SM species from milk and egg function through different mechanisms.Support or Funding InformationSupported by the University of Connecticut.