Susan K. Fried, Ph.D.

Professorfried_susan

Education:

Ph.D., Nutritional Biochemistry, Columbia University, 1980

Post-doctoral fellowships:

Emory University – Endocrinology – 1980-1982

Medical College of Pennsylvania – Lipid Biochemistry – 1982-3

General field of research:

Obesity & Adipose Tissue Biology

Affiliations other than medicine:

Evans Center for Interdisciplinary Biomedical Research

Section on Endocrinology, Diabetes and Nutrition, Dept of Medicine, BUSM

Director, Boston Nutrition and Obesity Research Center (BNORC)  (bnorc.org)

Director, Adipose Biology and Nutrient Metabolism Core, BNORC

Director, Affinity Research Collaborative on “Sex differences in Adipose Tissue and Obesity-related metabolic diseases”

 

Contact information:

Office and Lab

650 Albany St., Rm X815
Phone:  (617)-638 7110
Fax: (617)-638 7124

skfried@bu.edu

Research group information

Mi-Jeong Lee, Ph.D.  Instructor

Weimin Guo, Ph.D.    Post-doctoral fellow

Kalypso Karastergiou, M.D., Ph.D.

Yuanyuan Wu, Ph.D.


Keywords:

Obesity; Adipocyte translation; Inflammation; Insulin; Glucocorticoid

Summary of research interest:

Obesity, particularly abdominal obesity, confers increased risk for cardiovascular disease, type 2 diabetes, osteoarthritis, stroke and cancer. The long-term goal of research in my laboratory is to understand how fat deposition in different anatomical depots is regulated, and why abdominal obesity is associated with metabolic abnormalities. We are currently engaged in several projects that should shed light on these questions:

Regulation of leptin production: Adipocytes are now recognized as endocrine cells that produce a variety of hormones, including leptin, interleukin-6, and adiponectin. However, very little is known about the mechanisms that regulate the synthesis and secretion of adipose hormones (adipokines). We have focused our attention on leptin, an adipocyte hormone that regulates metabolism and appetite and is centrally involved in the regulation of body weight. Leptin production is increased in proportion to the amount of fat stored in the adipocyte. In addition, serum leptin levels change independent of adiposity, in response to changes in nutritional status. Our recent studies using human adipose tissue placed in organ culture and a rat model indicate that the nutritional regulation of leptin production is regulated, at least in part, by insulin, glucocorticoids, catecholamines and cytokines (Figure 1). Using metabolic labeling and immunopreciptation methods to monitor rates of leptin synthesis, turnover and secretion, we have demonstrated that pre- and post-transcriptional mechanisms are involved.  Reporter assays show that elements within the 5’ UTR of leptin stimulates, while the 3’UTR inhibits translation.  The insulin stimulation of leptin mRNA translation requires both UTRs.  Current studies are investigating the cis elements and transacting factors that mediate the nutritional regulation of leptin mRNA translation.

Depot differences in adipose tissue metabolism: We find significant differences in cytokine production in visceral (omental) adipose tissue. Interestingly, we find these cytokines are expressed mainly in stromal cells, not adipocytes. We are currently studying the hormonal regulation of cytokine production (TNFa, IL6 and 8) in human omental vs subcutaneous adipose tissue, as well as the metabolic effects of these cytokines on adipocyte metabolism and leptin production.

fried_nice-fat-cells

Recent publications:

Grahn TH, Zhang Y, Lee MJ, Sommer AG, Mostoslavsky G, Fried SK, Greenberg AS, Puri V. FSP27 and PLIN1 interaction promotes the formation of large lipid droplets in human adipocytes. Biochem Biophys Res Commun. 2013 Mar 8;432(2):296-301. doi: 10.1016/j.bbrc.2013.01.113. Epub 2013 Feb 8. PubMed PMID: 23399566; PubMed Central PMCID: PMC3595328.

Nimitphong H, Holick MF, Fried SK, Lee MJ. 25-hydroxyvitamin D₃ and 1,25-dihydroxyvitamin D₃ promote the differentiation of human subcutaneous preadipocytes. PLoS One. 2012;7(12):e52171. doi: 10.1371/journal.pone.0052171. Epub 2012 Dec 18. PubMed PMID: 23272223; PubMed Central PMCID: PMC3525569.

Karastergiou K, Fried SK, Xie H, Lee MJ, Divoux A, Rosencrantz MA, Chang RJ, Smith SR. Distinct developmental signatures of human abdominal and gluteal subcutaneous adipose tissue depots. J Clin Endocrinol Metab. 2013 Jan;98(1):362-71. doi: 10.1210/jc.2012-2953. Epub 2012 Nov 12. PubMed PMID: 23150689; PubMed Central PMCID: PMC3537084.

Lee MJ, Wu Y, Fried SK. Adipose tissue heterogeneity: mplication of depot differences in adipose tissue for obesity complications. Mol Aspects Med. 2013 Feb;34(1):1-11. doi: 10.1016/j.mam.2012.10.001. Epub 2012 Oct 13. PubMed PMID: 23068073; PubMed Central PMCID: PMC3549425.

Lee MJ, Fried SK. Glucocorticoids antagonize tumor necrosis factor-α-stimulated lipolysis and resistance to the antilipolytic effect of insulin in human adipocytes. Am J Physiol Endocrinol Metab. 2012 Nov 1;303(9):E1126-33. doi: 10.1152/ajpendo.00228.2012. Epub 2012 Sep 4. PubMed PMID: 22949029; PubMed Central PMCID: PMC3492859.

Karastergiou K, Smith SR, Greenberg AS, Fried SK. Sex differences in human adipose tissues – the biology of pear shape. Biol Sex Differ. 2012 May 31;3(1):13. doi: 10.1186/2042-6410-3-13. PubMed PMID: 22651247; PubMed Central PMCID: PMC3411490.

Lee MJ, Wu Y, Fried SK. A modified protocol to maximize differentiation of human preadipocytes and improve metabolic phenotypes. Obesity (Silver Spring). 2012 Dec;20(12):2334-40. doi: 10.1038/oby.2012.116. Epub 2012 May 4. PubMed PMID: 22627913.

Fried SK, Greenberg AS. Lipocalin 2: a “sexy” adipokine that regulates 17β-estradiol and obesity. Endocrinology. 2012 Apr;153(4):1582-4. doi: 10.1210/en.2012-1012. Epub 2012 Mar 9. PubMed PMID: 22408176; PubMed Central PMCID: PMC3320254.

Lee MJ, Gong DW, Burkey BF, Fried SK. Pathways regulated by glucocorticoids in omental and subcutaneous human adipose tissues: a microarray study. Am J Physiol Endocrinol Metab. 2011 Mar;300(3):E571-80. doi: 10.1152/ajpendo.00231.2010. Epub 2010 Dec 28. PubMed PMID: 21189358; PubMed Central PMCID: PMC3279304.

Lee MJ, Fried SK. 2009 Jun. Integration of hormonal and nutrient signals that regulate leptin synthesis and secretion. Am J Physiol Endocrinol Metab; 296(6):E1230-8.

Lee MJ, Fried SK, Mundt SS, Wang Y, Sullivan S, Stefanni A, Daugherty BL, Hermanowski-Vosatka A. 2008 Jun. Depot-specific regulation of the conversion of cortisone to cortisol in human adipose tissue. Obesity (Silver Spring); 16(6):1178-85.

Lee MJ, Wang Y, Ricci MR, Sullivan S, Russell CD, Fried SK. 2007 Mar. Acute and chronic regulation of leptin synthesis, storage, and secretion by insulin and dexamethasone in human adipose tissue. Am J Physiol Endocrinol Metab; 292(3):E858-64.

Lee MJ, Yang RZ, Gong DW, Fried SK. 2007 Jan 5. Feeding and insulin increase leptin translation. Importance of the leptin mRNA untranslated regions. J Biol Chem; 282(1):72-80.

Lee MJ, Fried SK. 2006 Sep. Multilevel regulation of leptin storage, turnover, and secretion by feeding and insulin in rat adipose tissue. J Lipid Res; 47(9):1984-93.

Yang RZ, Lee MJ, Hu H, Pollin TI, Ryan AS, Nicklas BJ, Snitker S, Horenstein RB, Hull K, Goldberg NH, Goldberg AP, Shuldiner AR, Fried SK, Gong DW. 2006 Jun. Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications. PLoS Med; 3(6):e287.

Yang RZ, Lee MJ, Hu H, Pray J, Wu HB, Hansen BC, Shuldiner AR, Fried SK, McLenithan JC, Gong DW. 2006 Jun.  Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. Am J Physiol Endocrinol Metab; 290(6):E1253-61.

Trujillo ME, Lee MJ, Sullivan S, Feng J, Schneider SH, Greenberg AS, Fried SK. 2006 Apr. Tumor necrosis factor alpha and glucocorticoid synergistically increase leptin production in human adipose tissue: role for p38 mitogen-activated protein kinase. J Clin Endocrinol Metab; 91(4):1484-90.

Technologies available for sharing upon request:

Collagenase isolation of adipocytes; Microarray data on human adipose tissues; Adipocyte culture