High-Fat Diet-Induced Adipose Tissue and Liver Inflammation and Steatosis in Mice Are Reduced by Inhibiting Sialidases.

High-fat diet (HFD)-induced inflammation and steatosis of adipose tissue and liver are associated with a variety of serious health risks. Sialic acids are found as the distal terminal sugar on glycoproteins, which are removed by sialidases (neuraminidases). In humans and mice, pulmonary fibrosis is associated with up-regulation of sialidases, and injections of sialidase inhibitors attenuate bleomycin-induced pulmonary fibrosis. Sialidase levels are altered in obese rodents and humans. This report shows that for mice on an HFD, injections of the sialidase inhibitor N-acetyl-2,3-dehydro-2-deoxyneuraminic acid inhibit weight gain, reduce steatosis, and decrease adipose tissue and liver inflammation. Compared with control, mice lacking the sialidase neuraminidase 3 have reduced HFD-induced adipose tissue and liver inflammation. These data suggest that sialidases promote adipose and liver inflammation in response to a high-fat diet.