In this video collection, authors of findings published in The Journal of Clinical Investigation present personally guided tours of their results. The journal accepts video submissions from authors of recently accepted manuscripts. Instructions can be found on the Author's Take Guidelines page.
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.
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.
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:
Brett Monia and Stefano Rivella discuss how reduction of TMPRSS6 expression with antisense oligonucleotides ameliorates iron metabolism disorders in mice. Highlights:
The liver secretes bile acids to aid in the digestion of fats. Cholestasis is a condition in which the bile flow from the liver to the duodenum is impeded. Patients with the disease exhibit itchiness (pruritis) and cannot sense pain (analgesia). The molecular mechanisms mediating these effects are unknown. Carlos Corvera of UCSF and Nigel Bunnett of Monash University discuss their study demonstrating that bile acids cause itch and analgesia by activating the TGR5 receptor in neurons. Highlights: