Actin related protein 2/3 complex subunit 1 up‐regulation in the hypothalamus prevents high‐fat diet induced obesity

Abstract

Obesity is a major health crisis in the modern society. Studies have shown that the consumption of a high‐fat diet (HFD) induces hypothalamic inflammation and leptin resistance, which consequently favours body mass gain. Actin related protein 2/3 complex subunit 1 (ARPC1B), an actin‐binding protein, is highly expressed in immune cells. Recent studies have shown that ARPC1B has a certain anti‐inflammatory effect. While ARPC1B expression is decreased in the hypothalamus of mice fed a HFD, the role of ARPC1B in HFD‐induced obesity remains unclear. Thus, we investigated whether ARPC1B up‐regulation in the hypothalamic arcuate nucleus (ARC) could inhibit the development of obesity. Herein, ARPC1B overexpression lentiviral particles were stereotaxically injected into the ARC of male C57BL/6J mice (7 weeks old) fed with HFD. Overexpression of ARPC1B in the hypothalamic ARC attenuated HFD‐induced ARC inflammation, reduced body‐weight gain and feed efficiency. Furthermore, up‐regulation of ARC ARPC1B improved the glucose tolerance and reduced subcutaneous/epididymal fat mass accumulation, which decreased the serum total cholesterol, serum triglyceride and leptin levels. In addition, upon ARPC1B overexpression in the hypothalamic ARC, intraperitoneal injection of leptin increased the phosphorylation level of signal transducer and activator of transcription 3 (STAT3), an important transcription factor for leptin's action, in the ARC of obese mice. Accordingly, we suggest that up‐regulation of ARPC1B in the hypothalamic ARC may improve the HFD‐induced hypothalamic inflammation and leptin resistance. Our findings demonstrate that ARPC1B is a promising target for the treatment of diet‐induced obesity.

The overexpression of actin related protein 2/3 complex subunit 1B(ARPC1B) promotes the ovarian cancer progression via activation of the Wnt/β-catenin signaling pathway

“…ARPC1B has been found to promote radiotherapy resistance and maintenance of the mesenchymal phenotype in glioma stem cells ( 12 ). Additionally, ARPC1B plays a crucial role in metabolism and the upregulation of ARPC1B in the hypothalamic arcuate nucleus has been linked to the improvement of high-fat diet induced hypothalamic inflammation and leptin resistance ( 26 ). The exploitation of cancer metabolism is providing new insight into cancer biology and can potentially lead to the development of more effective targeted treatments for patients ( 27 ).…”