Section: Research

Postdoctoral Position Available

Yong-Xu Wang, Ph.D.

Academic Role: Assistant Professor

Faculty Appointment(s) In:
   Program in Gene Function and Expression
   Program in Molecular Medicine

Other Affiliation(s):
   Interdisciplinary Graduate Program

Transcriptional Control of Energy Metabolism and Metabolic Diseases by the Nuclear Receptor PPAR Subfamily

Normal cellular energy metabolism is maintained through a delicate balance between energy intake and energy expenditure.  When energy intake exceeds energy expenditure, the extra energy is stored in the form of fat.  This energy imbalance is intimately linked to a cluster of metabolic diseases, including obesity, hyperlipidemia, and cardiovascular disease, as well as insulin resistance and type 2 diabetes.  Our laboratory is interested in understanding the transcriptional control of fatty acid and glucose metabolism by the PPAR subfamily of nuclear receptors.  PPARs are transcription factors and their activities can be regulated by dietary lipids and small synthetic compounds.  The three PPAR members (a, g, and d) display distinct tissue distribution profiles and together they control diverse metabolic processes, ranging from adipogenesis, lipogenesis, and lipid storage to oxidative metabolism.  Thus, these receptors serve as central molecular switches in metabolic regulation and are ideal drug targets for metabolic diseases.

We have recently demonstrated that PPARd powerfully promotes fat burning both in vivo and in cultured cells by activating multiple, coordinated programs involved in mitochondrial biogenesis, ß-oxidation, electron transfer chain, and energy uncoupling.  As a result, mice with an activated form of PPARd, or those treated with a PPARd agonist, are resistant to obesity and to insulin resistance and glucose intolerance induced by a high-fat diet. 

In a related study, we have investigated the role of PPARd in muscle fiber plasticity.  Skeletal muscle fibers are generally classified as either slow twitch (red muscle) or fast twitch (white muscle).  Slow twitch fibers are more fatigue-resistant than fast twitch fibers.  Endurance exercise training can provoke adaptive changes that convert fast twitch to slow twitch fibers.  We have found that simply expressing an activated form of PPARd in the skeletal muscle leads to a switch from fast twitch to slow twitch fibers, essentially mimicking the effects of endurance exercise training.  Functionally, the transgenic mice are able to run twice the distance of normal mice.  These data provide important molecular insight into the transcriptional control of muscle fiber plasticity pertinent to exercise training.  

Our current focus is to further dissect the functional roles of PPARs in normal physiology and metabolic diseases in a variety of metabolically active tissues, to understand the molecular mechanisms of their action, and to investigate their interactions with environmental factors and other signaling events.  A combination of tools, including molecular biology, mouse genetics, physiology and genomics, will be employed.

Office: LRB-517
Phone: 508-856-5647
E-mail: Yong.Wang@umassmed.edu
Keywords: Nuclear Receptors, Obesity, Diabetes, Molecular Physiology, Gene Regulation

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Postdoctoral Position Available A postdoctoral position is available to study in this laboratory. Contact Dr. Wang for additional details.