Workshop on Rare Syndromic Body Fat Disorders: What Can They Teach Us?

Event Details

Meeting Objectives

Studies of rare disorders affecting the amount and distribution of body fat provide opportunities to define previously unidentified genes and biological pathways involved in appetite regulation, adipose tissue biology, and energy homeostasis, and to provide novel insights into the myriad of mechanisms potentially contributing to obesity and its adverse consequences.

At this workshop, we will hear about several disorders (Prader-Willi syndrome, ciliopathies, and lipodystrophies) where patients/families have been identified and phenotyped, the causative mutations defined, and progress has been made in elucidating how the affected protein(s) and pathway(s) impact energy balance. We also hope to get an idea of the number of individuals/families with obesity and lipodystrophic syndromes where the genetic causes are unknown, and to learn what hurdles are commonly encountered when trying to find the causative mutations. Through presentations and discussions, we hope to encourage further investigation of cells from families with rare single gene or syndromic obesity disorders to learn about unknown biological pathways regulating energy balance, and to encourage further human research to shed light on why obesity occurs in some individuals with the "same" syndrome but not in others.

Meeting Organizers

Sadaf Farooqi, Cambridge University
Abhimanyu Garg, University of Texas Southwestern Medical Center
Jay Shendure, University of Washington
Carol Haft, Saul Malozowski, Sheryl Sato, and Phil Smith, NIDDK

Agenda

March 1, 2012

7:30 a.m. - 8:15 a.m.

Registration

8:15 a.m. - 8:30 a.m.

Welcome
Greg Germino, Deputy Director of NIDDK

8:30 a.m. - 9:15 a.m.

Obesity: Insights from Human Genetic Studies
Sadaf Farooqi, University of Cambridge

9:15 a.m. - 10:00 a.m.

Genetic Lipodystrophies: Disorders of Adipose Tissue Development, Differentiation, and Death
Abhimanyu Garg, The University of Texas Southwestern Medical Center

10:00 a.m. - 10:30 a.m.

Break

Session I: Pluses and Minuses of Models Used to Investigate Rare Fat Deposition Disorders

Moderator: Abhimanyu Garg
This session will highlight several different experimental systems used by investigators to elucidate the details of the molecular mechanism leading to altered fat deposition and obesity. Speakers should explain why the system used was chosen, and detail the advantages and limitations of the system.

10:30 a.m. - 11:00 a.m.

Brain-derived Neurotrophic Factor in WAGR Syndrome and Non-syndromic Obesity
Joan Han, National Institute of Child Health and Human Development

11:00 a.m. - 11:30 a.m.

Ciliopathies and Alterations of Fat Deposition - Mouse Work
Philip Beales, University College London

11:30 a.m. - 12:00 p.m.

Loss of Processed snoRNA (psnoRNA) Expression in Prader Willi Syndrome Changes Expression of Genes Involved in Energy Metabolism
Stefan Stamm, University of Kentucky

12:00 p.m. - 12:30 p.m.

Use of IPS Cells to Study Lipodystrophies and Other Diseases of Fat Deposition
Chad Cowan, Harvard University

12:00 p.m. - 2:00 p.m.

Lunch and Poster Session

Session II: Genetic Determinants of Metabolic Diseases

Moderator: Jay Shendure
This session will focus on recent technological advances in functional genomics and will address major challenges in identifying causal variants in human disease.

2:00 p.m. - 2:30 p.m.

Genetic Approaches for Finding Phenotypically Causal Variants in Human Disease
Jay Shendure, University of Washington

2:30 p.m. - 3:00 p.m.

Searching for Genes for the Metabolically Healthy Obese (and the Metabolically Unhealthy Lean) to Indentify New Physiological Pathways that Underlie Adiposity and Fat Deposition
Ruth Loos, Mount Sinai School of Medicine

3:00 p.m. - 3:15 p.m.

A Novel Null Mutation in Human Hormone Sensitive Lipase (HSL) Is Associated With Lipodystrophy, Dyslipidemia and Insulin Resistance
Coleen M. Damcott, University of Maryland School of Medicine

3:15 p.m. - 3:45 p.m.

Break

Several meeting participants with interesting patients/leads/mouse models taken from submitted abstracts will be asked to present a few background slides, which will then be followed by a discussion with the group about what could be done to move these projects forward.

3:45 p.m. - 5:15 p.m.

Mice Deficient of the Inflammatory Gene - FAT10 Display Markedly Reduced Fat Formation and Increased Longevity
Allon Canaan, Yale University School of Medicine

Characterization of New Non-Coding RNAs that Regulate Genes Involved in Fat/Energy Metabolism
Marian Falaleeva, University of Kentucky

A Novel Mouse Model of Combined Lipomatosis and Partial Lipodystrophy Reveals White Adipocytes Arise from Myf5+ Precursors
David Guertin, University of Massachusetts Medical School

XL α s Antagonizes Metabolic Control by Gs α In Vivo
Ahmed Kablan, National Institutes of Diabetes, Digestive, and Kidney Diseases, NIH

5:15 p.m.

Adjournment

March 2, 2012

7:30 a.m. - 8:15 a.m.

Registration

Session III: Pleiotropic "Obesity Syndromes"

Moderator: Philip Beales
This session will examine rare genetic syndromes for which obesity is manifest in many but not all individuals. Speakers should explore possible mechanisms underlying the variable expression of obesity in these syndromes.

8:15 a.m. - 8:45 a.m.

Obesity and Associated Traits in Alstrom Syndrome
Jurgen Naggert, The Jackson Laboratory

8:45 a.m. - 9:15 a.m.

Obesity and X-linked Mental Retardation: Mechanistic Insights into Borjeson-Forssman-Lehmann Syndrome
David Picketts, Ottawa Hospital Research Institute

9:15 a.m. - 9:45 a.m.

Imprinting, Brain Development, and Pleiotropy of 15q11-q13 Disorders
Janine M. LaSalle, University of California, Davis, School of Medicine

9:45 a.m. - 10:15 a.m.

Break

Session IV: Treatment of Rare Syndromic Body Fat Disorders

Moderator: Jack Yanovski
This session will explore approaches being taken to develop effective treatments for rare, sometimes pleiotropic "obesity syndromes." Speakers should comment on some of the challenges encountered in trying to treat rare diseases involving multiple pathways and tissues even when the cellular defect is known.

10:15 a.m. - 10:45 a.m.

NIH Resources to Aid in the Development of Therapeutics
Gurmit Grewal, National Center for Advancing Translational Sciences (NCATS)

10:45 a.m. - 11:00 a.m.

Pharmacological Chaperones: Potential Therapeutic Approach to Treat MC4R-Linked Early Onset Obesity
Patricia Reno, University of Montreal

11:00 a.m. - 11:15 a.m.

Biochemical and Molecular Characterization of the Serotonin Receptor 2C (HTR2C) in Energy Homeostasis Control
Manli Shen, University of Kentucky

11:15 a.m. - 11:45 a.m.

Rare Mutations in the Leptin-Melanocortin Pathway: Implications for the Treatment of Obesity
Christian Vaisse, University of California, San Francisco

11:45 a.m. - 12:15 p.m.

Learning on the Job in Lipodystophy: Going from Therapy to Pathophysiology
Elif Oral, University of Michigan

12:15 p.m. - 12:45 p.m.

Identification of Allosteric Modulators of the MC4 Receptor for Treatment of Melanocortin Obesity Syndrome
Roger Cone, Vanderbilt University

12:45 p.m. - 1:00 p.m.

Closing Remarks

1:00 p.m.

Adjourn