title: Anti-HMGB1 antibody reduces weight gain in mice fed a high-fat diet.
abstract: 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.
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: V N
authors.initials: VN
authors.lastname: Montes
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Subramanian
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Goodspeed
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Wang
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Omer
authors.affiliation: BakerIDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Bobik
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Teshigawara
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nishibori
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Chait