TY - JOUR
T1 - Anti-HMGB1 antibody reduces weight gain in mice fed a high-fat diet
AU - Montes, V. N.
AU - Subramanian, S.
AU - Goodspeed, L.
AU - Wang, S. A.
AU - Omer, M.
AU - Bobik, A.
AU - Teshigawara, Kiyoshi
AU - Nishibori, M.
AU - Chait, A.
N1 - Funding Information:
The study was funded in part by NIH K01HL118711, NORC P30DK035816 and the Nutrition, Obesity and Atherosclerosis T32HL007028 grants.
Publisher Copyright:
© 2015 Macmillan Publishers Limited.
PY - 2015/6/15
Y1 - 2015/6/15
N2 - Insulin resistance in obesity is believed to be propagated by adipose tissue and liver inflammation. HMGB1 is a multifunctional protein that is pro-inflammatory when released from cells. It has been previously demonstrated that anti-HMGB1 antibody reduces atherosclerotic lesion pro-inflammatory cells and progression of atherosclerosis in a mouse model. To test the potential beneficial role of blocking HMGB1 in adipose tissue and liver inflammation in mice fed an obesogenic diet, we administered anti-HMGB1 antibody to C57Bl/6 mice fed a high (60%)-fat diet. The mice were treated with weekly injections of an anti-HMGB1 antibody or anti-KLH antibody (isotype control) for 16 weeks. Mice that received the anti-HMGB1 antibody gained less weight than the control-treated animals. Anti-HMGB1 treatment also reduced hepatic expression of TNF-alpha and MCP-1, molecules that promote inflammation. However, adipose tissue inflammation, as measured by gene expression analyses and immunohistochemistry, did not differ between the two groups. There also were no differences in glucose or insulin tolerance between the two groups. When feeding mice a high-fat diet, these data suggest that HMGB1 may have a crucial role in weight gain and liver inflammation.
AB - Insulin resistance in obesity is believed to be propagated by adipose tissue and liver inflammation. HMGB1 is a multifunctional protein that is pro-inflammatory when released from cells. It has been previously demonstrated that anti-HMGB1 antibody reduces atherosclerotic lesion pro-inflammatory cells and progression of atherosclerosis in a mouse model. To test the potential beneficial role of blocking HMGB1 in adipose tissue and liver inflammation in mice fed an obesogenic diet, we administered anti-HMGB1 antibody to C57Bl/6 mice fed a high (60%)-fat diet. The mice were treated with weekly injections of an anti-HMGB1 antibody or anti-KLH antibody (isotype control) for 16 weeks. Mice that received the anti-HMGB1 antibody gained less weight than the control-treated animals. Anti-HMGB1 treatment also reduced hepatic expression of TNF-alpha and MCP-1, molecules that promote inflammation. However, adipose tissue inflammation, as measured by gene expression analyses and immunohistochemistry, did not differ between the two groups. There also were no differences in glucose or insulin tolerance between the two groups. When feeding mice a high-fat diet, these data suggest that HMGB1 may have a crucial role in weight gain and liver inflammation.
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U2 - 10.1038/nutd.2015.11
DO - 10.1038/nutd.2015.11
M3 - Article
AN - SCOPUS:84935894752
VL - 5
JO - Nutrition and Diabetes
JF - Nutrition and Diabetes
SN - 2044-4052
M1 - e161
ER -