Sitosterol prevents obesity-related chronic inflammation

Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Feb;1863(2):191-198. doi: 10.1016/j.bbalip.2017.12.004. Epub 2017 Dec 6.

Abstract

The physiological roles of phytosterols in chronic inflammation, which are believed to be involved in the underlying mechanisms for metabolic diseases, have yet to be elucidated. Therefore, in the present study, we aimed to elucidate the physiological roles of phytosterols in both clinical studies and animal experiments. We observed the existence of rather specific negative correlations between the serum sitosterol level and the serum IL-6 and the TNF-α levels in both diabetic subjects (n=46) and non-diabetic subjects (n=178). Multiple regression analyses also revealed that the serum IL-6 and TNF-α levels exhibited strong negative correlations with the serum sitosterol levels. When ABCG5/8 KO mice with markedly elevated plasma sitosterol levels and ABCG5/8 hetero mice were fed a high-fat diet, we observed that the increase in body weight, the fatty liver changes, and the expansion of perigonadal adipose tissues were suppressed in ABCG5/8 KO mice without any modulation of food intake. We also observed that the plasma IL-6 and TNF-α levels, the expressions of TNF-α and PAI-1 in the liver and the expressions of the IL-6, TNF-α, and MCP-1 levels in the adipose tissue were lower in ABCG5/8 KO mice. These results suggest that sitosterol might suppress obesity-related chronic inflammation and might be applicable to the treatment of metabolic diseases.

Keywords: ABCG5/8; Chronic inflammation; IL-6; Sitosterol; TNF-α.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 5 / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 5 / metabolism
  • Animals
  • Chronic Disease
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / prevention & control
  • Interleukin-6 / blood*
  • Lipoproteins / genetics
  • Lipoproteins / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Obesity* / blood
  • Obesity* / drug therapy
  • Sitosterols* / administration & dosage
  • Sitosterols* / pharmacokinetics
  • Tumor Necrosis Factor-alpha / blood*

Substances

  • ABCG5 protein, mouse
  • ATP Binding Cassette Transporter, Subfamily G, Member 5
  • IL6 protein, human
  • Interleukin-6
  • Lipoproteins
  • Sitosterols
  • Tumor Necrosis Factor-alpha
  • gamma-sitosterol