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Publication
The kielin/chordin-like protein (KCP) attenuates high-fat diet-induced obesity
and metabolic syndrome in mice.
Authors Soofi A, Wolf KI, Emont MP, Qi N, Martinez-Santibanez G, Grimley E, Ostwani W,
Dressler GR
Submitted By Submitted Externally on 4/24/2018
Status Published
Journal The Journal of biological chemistry
Year 2017
Date Published 6/1/2017
Volume : Pages 292 : 9051 - 9062
PubMed Reference 28424263
Abstract Obesity and its associated complications such as insulin resistance and
non-alcoholic fatty liver disease are reaching epidemic proportions. In mice,
the TGF-ß superfamily is implicated in the regulation of white and brown adipose
tissue differentiation. The kielin/chordin-like protein (KCP) is a secreted
regulator of the TGF-ß superfamily pathways that can inhibit both TGF-ß and
activin signals while enhancing bone morphogenetic protein (BMP) signaling.
However, KCP's effects on metabolism and obesity have not been studied in animal
models. Therefore, we examined the effects of KCP loss or gain of function in
mice that were maintained on either a regular or a high-fat diet. KCP loss
sensitized the mice to obesity and associated complications such as glucose
intolerance and adipose tissue inflammation and fibrosis. In contrast,
transgenic mice that expressed KCP in the kidney, liver, and adipose tissues
were resistant to developing high-fat diet-induced obesity and had significantly
reduced white adipose tissue. Moreover, KCP overexpression shifted the pattern
of SMAD signaling in vivo, increasing the levels of phospho (P)-SMAD1 and
decreasing P-SMAD3. Adipocytes in culture showed a cell-autonomous effect in
response to added TGF-ß1 or BMP7. Metabolic profiling indicated increased energy
expenditure in KCP-overexpressing mice and reduced expenditure in the KCP
mutants with no effect on food intake or activity. These findings demonstrate
that shifting the TGF-ß superfamily signaling with a secreted protein can alter
the physiology and thermogenic properties of adipose tissue to reduce obesity
even when mice are fed a high-fat diet.




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