Whereas white adipose tissue depots contribute to the development of metabolic diseases, brown and beige adipose tissue has beneficial metabolic effects. Here we show that CDK6 regulates beige adipocyte formation. We demonstrate that mice lacking the CDK6 protein or its kinase domain (K43M) exhibit significant increases beige cell formation, enhanced energy expenditure, better glucose tolerance, and improved insulin sensitivity, and are more resistant to high-fat diet-induced obesity. Re-expression of CDK6 in Cdk6−/− mature or precursor cells, or ablation of RUNX1 in K43M mature or precursor cells, reverses these phenotypes. Furthermore, RUNX1 positively regulates the expression of Ucp-1 and Pgc1α by binding to proximal promoter regions. Our findings indicate that CDK6 kinase activity negatively regulates the conversion of fat-storing cells into fat-burning cells by suppressing RUNX1, and suggest that CDK6 may be a therapeutic target for the treatment of obesity and related metabolic diseases.
The core requirements for point-of-care (POC) diagnostics necessitate low-cost, portability, easily integrated sample preparation, and quick measurement time. Frequency-shift based magnetic sensing is a measurement technique utilizing a complementary metal-oxide-semiconductor (CMOS) integrated-circuit (IC) chip for magnetic label detection. The sensing scheme leverages the low-cost manufacturing of IC chips while demonstrating the potential for multiplexing capabilities. In this article, we present modifications to this scheme for POC viability. We introduce a handheld reusable reader and a disposable open-well cartridge for the detection of nucleic acids and antigens. The diagnostic system utilizes a novel "magnetic freezing" technique to reduce measurement time, obviates baseline measurement before or during biological assay, and reduces sensor noise. We utilize these enhancements for the room temperature, amplification-free detection of a 31 base-pair DNA oligomer and the interferon-γ (IFN-γ) protein. We have demonstrated reliable measurements down to 100 pM for the DNA assay and 1 pM for the protein.
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