Obesity, diabetes, and other metabolic diseases have known underlying genetic causes; however, environmental factors also play an important role in the onset and development of metabolic dysfunction. In this episode, Mitchell Lazar and Raymond Soccio discuss their study, which compared high fat-diet-induced effects on gene expression and the epigenome in mice genetically prone to diet-induced obesity and in animals that are resistant to diet-induced metabolic disease. They find that the thermogenic gene Ucp1 is repressed in the obesity-prone mice, but that either cold-exposure or treatment with the insulin-sensitizing drug rosiglitazone restores Ucp1 expression to levels similar to that in obesity-resistant strains. The results of this study demonstrate that genetic defects in metabolism can be rescued by environmentally-driven epigenomic modifications.
Eric Olson’s pivotal research in the field of molecular biology has uncovered the mechanisms that control cardiac and skeletal muscle development. His current work focuses on finding new treatments for muscular dystrophies, potential regenerative approaches for cardiac and skeletal muscle, and the role of epigenetic mechanisms as regulators of muscle development. Dr. Olson currently holds the Annie and Willie Nelson Professorship in Stem Cell Research at the University of Texas Southwestern Medical Center and is himself a talented musician. This month, in a conversation with JCI Editor at Large Ushma Neill, he discusses how creativity and a love of discovery have driven his career in science and what it was like to meet Willie Nelson.
PET allows noninvasive visualization of several physiological, neurochemical, and pharmacological processes within patients. Application of PET in the brain has been limited due to a lack of radiotracers that label specific neurons or regions. In this episode, Jacob Hooker, Mark Alberts, and Genevieve C. Van de Bittner describe the discovery and characterization of [11C]GV1-57 (Neuroflux), which specifically labels mature olfactory sensory neurons in the olfactory epithelium. This radiotracer has potential as a powerful tool for monitoring olfactory neurogenesis under both normal and disease states.
The hormone kisspeptin is essential for reproductive function, an effect that is mediated by its actions in the hypothalamus. Recent studies suggest that kisspeptin and its receptor are also expressed in other regions of the brain; however, little is known about the effects of this hormone in the brain in regions outside of the hypothalamus. In this episode, Waljit Dhillo and colleagues evaluate limbic system-specific effects of kisspeptin administration in healthy male volunteers. The data from this study indicate that kisspeptin action in the limbic system mediates sexual and emotional brain processing.
Aminoglycoside antibiotics can damage the hair cells of the inner ear, leading to hearing loss and balance disorders. Improved treatment paradigms have reduced the risk of adverse effects associated with these antibiotics, but permanent inner ear damage is still common. Hair cells are susceptible to damage because of their tendency to take up and retain aminoglycosides, whereas less vulnerable cells do not accrue aminoglycosides after exposure. To better understand the mechanisms that contribute to aminoglycoside toxicity, David Raible’s lab at the University of Washington imaged fluorescently-labeled aminoglycosides in the hair cells of live zebrafish. They found that the degree of aminoglycoside-induced toxicity was linked to how rapidly the antibiotic was distributed into lysosomes, suggesting that monitoring the kinetics of lysosomal delivery may be an effective way to evaluate different aminoglycoside treatment paradigms.
In the accompanying video, a time-lapse of zebrafish hair cells (green) shows the transit of fluorescently-labeled aminoglycosides (red) from the intracellular space into lysosomes. At the beginning of the video, aminoglycosides are visible as a diffuse pool in the cytosol. Within 20 minutes, the diffuse signal decreases as aminoglycosides merge into puncta, indicating their uptake into lysosomes.