Boston University Medical Campus
Evans Center for Interdisciplinary Biomedical Research

SEX DIFFERENCES IN ADIPOSE TISSUE BIOLOGY AND METABOLIC DISEASE

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:

Sexually dymorphic patterns of fat distribution and remodeling correlate with risk for metabolic diseases. While central or upper body obesity, typical of males, increases risk for insulin resistance and cardiometabolic risk, the amount of lower body (gluteo-femoral adipose tissue) that is typical of pear-shaped women, independently diminishes risk.  Our team of basic and translational researchers in Endocrinology, Biochemistry, Cardiology/vascular biology, cancer research/cell differentiation (BMC), and Bioinformatics (CRC) is poised address the basic mechanisms involved in regulating sex-specific patterns of fat distribution and metabolism. To address possible cell autonomous differences in male and female adipocytes, we propose fat transplantation studies. We will analyze the consequences of transplanting visceral and sc adipocyte tissue (or adipose precursors) to the peritoneal or sc compartment (female to female and female to male). Preliminary analysis will focus on establishing phenotypes of transplanted and endogenous adipose tissues (metabolic, blood flow, gene expression, histology, innervation, remodeling/inflammation) and the animal (glucose tolerance, circulating factors). We will also initiate characterization of human M and F derived adipose precursors in vitro and after transplantation. To guide our work, we will also conduct specialized bioinformatics analysis of sex-biased gene networks in our existing datasets. To foster the application of new technologies (e.g epigenetic, proteomics, metabolomics, genomic, hESC) to address questions that arise as we gather data, we will continue group meetings with presentations by ARC members and guests. This ARC project should expand existing collaborations in novel directions and establish new interdisciplinary ones for PPGs.

ARC Members:

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

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)

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.