University of California, USA
Title: Genome-wide expression analysis in hypothalamus of obese mice fed a high fat diet
Margarita C Curras-Collazo completed her PhD in Medical Physiology from The Ohio State University and later pursued postdoctoral studies in neuropharmacology at the University of North Carolina, Chapel Hill and Emory University. She is an Associate Professor of Neuroscience at the University of California, Riverside. Research in the Curras-Collazo lab focuses on homeostatic functions of the neuroendocrine hypothalamus as well as the neurotoxicological and endocrine disruptive effects of environmental pollutants. She has published more than 35 papers in reputed journals and has served as an ad hoc reviewer for NSF, American Heart Association, and DOD as well as international agencies.
It is well established that the intake of fatty foods induces obesity, although relatively little attention is given to the type of fat. We show that male C57/BL6 mice fed a high fat diet (HFD) for 24 weeks based on coconut oil (saturated fat) had significantly less weight gain than mice fed HFD enriched in soybean oil, which is rich in the polyunsaturated omega-6 fatty acid linoleic acid (LA-HFD). LA-HFD mice also exhibited diabetes and insulin resistance. We performed genome-wide expression profiling (RNAseq) on the hypothalamus from these mice (n=4/group) and found significant changes in 47 genes. Of these, only Sema3e and Sod1 have been previously linked to obesity or diabetes. Oxt and other candidate genes showed significant changes. Elevated expression of Sod1 (superoxide dismutase 1) in LA-HFD mice is consistent with the established role that oxidative stress plays in the progression of diabetes. Sema3e, which encodes class 3 semaphorin E proteins, showed a significant 1.7-fold decrease in expression in LA-HFD brains compared to HFD mice. In the brain Sema3e and its receptor Plexin D1 have an established role in axon-guidance and neurodevelopment, but have not been linked to energy balance. However, Sema3e within obese adipose tissue has been shown to interfere with leptin signaling, contributing to insulin resistance: our finding suggests a potential bidirectional partnership within the adipose-brain axis. We conclude that in the context of a diet high in saturated fats, soybean oil may contribute to obesity and associated changes in hypothalamic genes related to obesity and diabetes.