Sex Differences in Adipose Tissue Biology and Related Metabolic Diseases

INITIATION DATE:

12.01.09

ARC DIRECTORS AND CO-DIRECTORS:

Susan K. Fried, PhD; Director; Professor; Medicine/ Endocrinology

Paul Pilch, PhD; Co-Director; Professor; Biochemistry

OVERVIEW OF GOALS AND MISSION:

Abstract

The ARC focuses on the role of adipose tissue biology in the metabolic complications of obesity in men and women.  Our members have complementary expertise in biochemistry, cell biology, immunology and translational research in obesity, diabetes and cardiovascular disease.  As a graduating ARC with a close relationship to an existing NIH-funded center, the Boston Nutrition and Obesity Research Center, we have initiated novel collaborations that resulted in interdisciplinary grant proposals, including ‘brite’ adipocytes, adiporedoxin, a novel regulator adipocyte secretory function and adipocyte dysfunction in insulin resistance. We also engaged in fruitful ARC*ARC collaborations with four other ARCS: Mitochondria, Arterial Stiffness, Cancer and Inflammation, and Metabolic Disease and Insulin Resistance: Studies in Patients Undergoing Bariatric Surgery.  There is substantial overlap in the membership of these ARCs, which reflect growing collaborations and common interests to enrich the training experiences of graduate and post-doctoral trainees.  Thus, we hope to continue to sponsor multidisciplinary seminars and workshops to develop these collaborations and spark new ones.

ARC Members:

Name/Title (*key personnel) Dept/School Role in ARC
Susan K Fried* Medicine, Endocrinology, Diabetes & Nutrition, BUSM Director
Paul Pilch* Biochemistry, BUSM Director
Caroline Apovian Medicine, Endocrinology, Diabetes & Nutrition, BUSM Investigator
Tamar Aprahamian* Medicine, Renal, BUSM Investigator
Barbara Corkey Medicine, GI, BUSM Investigator
Andrea Coviello Medicine, Endocrinology, Diabetes & Nutrition, BUSM Investigator
Gerald Denis Cancer Center, BU Investigator
Stephen Farmer* Biochemistry, BUSM Investigator
Andrew S. Greenberg* Tufts U, HNRC Collaborator
Ulla Hansen* BU-Biology, CRC Investigator
Nawfal Istfan* Endocrinology, Diabetes & Nutrition BUSM Investigator
Kostya Kandror Biochemistry, BUSM Investigator
Simon Kasif Bioinformatics, CRC Investigator
Igor Kramnik Immunology, BUSM Investigator
Matt Layne Biochemistry, BUSM Investigator
Mi-Jeong Lee* Medicine, Endocrinology, Diabetes & Nutrition BUSM Investigator
Karen K. Miller Endocrinology, MGH Collaborator
Barbara Nikolajczyk Medicine, Microbiology, BUSM Investigator
Valentina Perissi Biochemistry, BUSM Investigator
Vishwajeet Puri* Medicine, Endocrinology, Diabetes & Nutrition BUSM Investigator
Barbara Schreiber Biochemistry, BUSM Investigator
Steven Smith* Burnham Inst, Florida Hospital Collaborator
David Waxman Cell and Molecular Biology, BU-CRC Investigator

 

MAIN ARC PROJECT(S) FOR 2009-2010:

Our group has decided to pursue three objectives that we envision will serve as a new platform to produce preliminary data and evidence of collaborations for planned PPGs.

1. Establish and utilize a mouse model (fat transplantation) to determine cell autonomous sex-related differences in adipocyte and adipose tissue biology with a focus on mechanisms underlying the protection of females from adipose tissue inflammation/remodeling events.

2. Identify sex-biased and depot-specific differences in gene expression networks that are common in mouse and human (bioinformatic analysis of existing and emerging datasets).

3. Establish phenotypic characteristics (growth, differentiation) of preadipocytes (adipose stem cells) culture of male and female-derived adipocytes from human adipose depots, and their morphology. Plans for year 2-3 will analyze the metabolic effects of human adipose tissue or preadipocytes of different depot and Mvs. F origin when transplanted into immune-compromised rodents.

ARC AS A RESOURCE:

-Microarray results from visceral adipose tissues of male and female mice and humans

-Adipose Tissues,  preadipocyte or other stromal-derived cultures, and their products (e.g conditioned media) from male and female mice and humans

AIM:  We plan seminars and activities, co-sponsored by BNORC, to foster the translation of basic research in adipose tissue biology and obesity using cell and mouse models.  We focus on topics that bring together multiple ARCs.

–       The Annual Program of BNORC will focus on Nutrition, obesity and the microbiome, a topic of keen interest to the Bariatric ARC as well as ours.

–       We will also continue seminars around the interface of CVD, Insulin resistance and Obesity in men and women that was highlighted in our recent symposium on Brain Control of Sympathetic Function and Cardiovascular Function.

–       Browning, britening, and whitening of adipocytes. This topic involves active collaborations with the MitoARC.

Our central goal is to bring together researchers on the BUMC and BU to accelerate conversations on topics related to obesity and related disease.  The goal is innovative integrative collaborations to address this very difficult to study disease at basic and translational levels.

Pictures, Images, Figures:

Venn diagram illustrating sex and depot-dependent difference in gene expression in adipose tissues (gonadal fat (GF) and inguinal subcutaneous fat (IF) of mice fed a high fat diet to induced obesity. Note that relatively few of the genes that are differentially expressed are common to both depots. (Clegg, Grove, Fried, Greenberg, et al., IJO In press)
Venn diagram illustrating sex and depot-dependent difference in gene expression in adipose tissues (gonadal fat (GF) and inguinal subcutaneous fat (IF) of mice fed a high fat diet to induced obesity. Note that relatively few of the genes that are differentially expressed are common to both depots. (Clegg, Grove, Fried, Greenberg, et al., IJO In press)
Gonadal steroids like contribute to sex differences in fat distribution in males and females through epigenetic effects and direct actions on adipose tissue growth, inflammation, metabolic and endocrine functions.
Gonadal steroids like contribute to sex differences in fat distribution in males and females through epigenetic effects and direct actions on adipose tissue growth, inflammation, metabolic and endocrine functions.