Videos
Brown adipose tissue (BAT), which mediates non-shivering thermogenesis, contributes to whole body energy expenditure and weight regulation in rodents. Given the tissue's high energy consumption, understanding the mechanisms that drive BAT recruitment and activation could be useful in the development of novel anti-obesity therapies. In this episode of Author's Take, Takeshi Yoneshiro and Masayuki Saito discuss their recent study in which subjects exposed subjects to a daily cold stimulus for 6 weeks had increased BAT activation and reduced overall fat mass. Yoneshiro and colleagues also observed that treatment with capsinoids, the spicy compounds found in chili peppers, resulted in BAT accumulation and increased energy expenditure in individuals who previously had low or undetectable BAT. These results suggest that methods to increase BAT levels could be used to fight obesity.
Natural genetic variants in the 3’ untranslated region of NPPA, the gene that encodes the vasodilator atrial natriuretic peptide (ANP), have previously been linked to blood pressure. Pankaj Arora and colleagues found that individuals with the AG genotype had up to 50% higher levels of ANP when fed a high salt diet compared to individuals with the AA genotype. Additionally, they identified a microRNA, miR-425, that is expressed in human atria and ventricles. Arora and colleagues demonstrated that miR-425 silenced NPPA mRNA encoded by the A allele, but not the G allele. These findings indicate that therapeutics targeting miR-425 could potentially be used to increase ANP levels to treat salt-induced hypertension.
In this episode of JCI's Author's Take, Donald Kohn of UCLA describes his group's efforts to develop a method to safely and effectively modify patient bone marrow to treat sickle cell disease. Sickle cell disease (SCD) is an autosomal recessive disorder caused by mutations in hemoglobin (HBB) that leads to rigid, deformed red blood cells, as seen in the accompanying image. A small number of patients have been successfully treated with allogeneic hematopoietic stem cell (HSC) transplantation; however, there are several drawbacks and complications associated with this procedure. Many complications could potentially be avoided by performing an autologous HSC transplant in combination with gene therapy to over-ride the defective hemoglobin gene. Zulema Romero, Donald Kohn, and colleagues investigated the utility of a lentiviral vector encoding a human b-globin gene engineered to impede sickle hemoglobin polymerization. The vector efficiently transduced bone marrow cells from SCD patients and expressed the engineered globin gene to prevent sickling of red blood cells and the transduced cells were successfully transplanted into immunocompromised mice, indicating that this method could potentially be used to treat SCD.
Dr. Christine Seidman of the Harvard Medical School has uncovered the genetic basis of many human cardiovascular disorders, from cardiomyopathy and heart failure to congenital heart malformations. In this interview, she speaks about her early intrigue with atrial natriuretic factor and her more current gene-intensive investigations. She also shares many more stories about her interest in the ear, an early inspirational patient, and her thoughts on work-life balance.
Tsonwin Hai and colleagues discuss how the transcription factor ATF3 acts as a key regulator of the host immune response and as a contributor to co-option of the host by cancer cells to promote metastasis. Highlights:
- ATF3 is expressed in immune mononuclear cells in human breast tumors and is associated with worse clinical outcomes.
- Host ATF3 expression facilitates breast cancer metastasis.
- ATF3 alters the host systemic environment, increasing the number of tumor-associated macrophages.
- Cancer-induced ATF3 expression in mononuclear cells alters gene expression and bioactivity to contribute to host-enhanced metastasis.
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