Susan K Fried

Susan K Fried
Boston University | BU · Boston Nutrition Obesity Research Center

PhD

About

164
Publications
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Publications

Publications (164)
Article
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IMPACT: Characterizing the cellular composition of human adipose tissue may contribute to the prevention and/or treatment of obesity-associated metabolic diseases. OBJECTIVES/GOALS: Our aims in this study were to use single-cell techniques 1. to characterize cell types within the stromavascular fraction of human adipose tissue, 2. to identify subse...
Article
Objective The purpose of this study was to investigate the effects of vitamin D on adipokine expression and inflammation in human adipose tissues and adipocytes and evaluate the molecular mechanisms involved. Methods Omental and abdominal subcutaneous human adipose tissues were treated with 1,25‐dihydroxyvitamin D3 (1,25(OH)2D3), and adipokine lev...
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Treatment with PPARγ agonists in vivo improves human adipocyte metabolism, but the cellular mechanisms and possible depot differences in responsiveness to their effects are poorly understood. To examine the ex vivo metabolic effects of rosiglitazone (Rosi), we cultured explants of human visceral (omental) and abdominal subcutaneous adipose tissues...
Article
Visceral obesity is associated with insulin resistance and higher risk of type 2 diabetes and metabolic diseases. A limited ability of adipose tissues to remodel through the recruitment and differentiation of adipose stem cells (ASCs) is associated with adipose tissue inflammation and fibrosis and the metabolic syndrome. We show that the lower adip...
Article
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White adipose tissue expands through both adipocyte hypertrophy and hyperplasia and it is hypothesized that fibrosis or excess accumulation of extracellular matrix within adipose tissue may limit tissue expansion contributing to metabolic dysfunction. The pathways that control adipose tissue remodeling are only partially understood, however it is l...
Data
ACLP expression localizes with pericellular ECM deposition. A, epididymal adipose tissue from C57BL6/J male mice on low fat diet or high fat diet for 16 weeks (n = 3 for each diet group) was excised and fixed with methyl Carnoy, stained with picrosirius red and imaged using brightfield (left panels) and under polarized light (right panels). B, Tiss...
Data
Primer sequences of genes analyzed by qPCR. (EPS)
Chapter
Sex differences in adipose tissue distribution and the metabolic, endocrine, and immune functions of different anatomical fat depots have been described, but they are incompletely documented in the literature. It is becoming increasingly clear that adipose depots serve distinct functions in males and females and have specific physiological roles. H...
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Men and women are different in their fat mass and distribution pattern. The gynoid-type fat distribution, accumulation in lower-body, is considered to be protective while the android-type accumulation in upper-body, both in abdominal subcutaneous and visceral depots, is detrimental. Sex-dependent depot differences in adipose metabolic and endocrine...
Article
Objective: Lower body fat is associated with diminishing cardiometabolic risk. Physiological differences between gluteofemoral and abdominal subcutaneous adipocyte functions are known, but the molecular basis for depot differences in adipocyte function is poorly understood. The objective of this study was to identify depot differences in microRNA...
Article
Objective: To investigate the effects of short-term GH administration on abdominal subcutaneous adipocyte size and CT attenuation in men with abdominal obesity. Design: 6-week, randomized, double-blind, placebo-controlled study of GH (starting dose 2μg/kg/d) vs placebo of 15 abdominally obese men (mean age: 34±6years; mean BMI: 37.7±6.1kg/m(2),...
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Glucocorticoids promote fat accumulation in visceral compared to subcutaneous depots, but the molecular mechanisms involved remain poorly understood. To identify long-term changes in gene expression that are differentially sensitive or responsive to glucocorticoids in these depots, paired samples of human omental (Om) and abdominal subcutaneous (Ab...
Data
Lists of pathways identified by GSEA as up- or down-regulated by each concentration of Dex in both depots (S2A and S2B, respectively), or only in 1 depot by Dex (S2C). Gene lists for each depots were preranked by fold change vs. 0 nM Dex and analyzed by GSEA, as described in Methods. FDRq values < 0.05 were considered statistically significant. (XL...
Data
Lists of the 460 transcripts used for cluster analysis in Fig 3. Genes exhibiting significant Depot × [Dex] interaction (p < 0.05) were used for this cluster analysis. Cluster and sub-cluster numbers as well as LME results and expression values are given for each gene [Data are the mean of the expression values (linearized scale) for the 3 paired s...
Data
Dendrogram of 2 way cluster analysis of transcripts exhibiting a Depot*[Dex] interaction. The intensity of the red or blue color in each row represents expression values, high or low respectively, which were scaled across both depots, and each column represents the culture condition (culture with 0, 1, 10, or 1000 nM Dex is designated Om0, Om1, Om1...
Data
Expression values for all transcripts in the microarray. Averages of expression values (linear scale) at each Dex concentration are given (average values of n = 3 subjects). FDRq for LME parameters (Depot, [Dex], and Depot*[Dex] interaction) are given for each gene. (XLSX)
Article
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Increased adipocyte size is hypothesized to signal the recruitment of adipose progenitor cells (APCs) to expand tissue storage capacity. To investigate depot- and sex-differences in adipose growth, male and female C57BL/6J mice (10-weeks-old) were challenged with high fat (HF) or low fat (LF) diets (D) for 14 weeks. The HFD increased gonadal (GON)...
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Objective: Insulin signaling plays a unique role in the regulation of energy homeostasis and the impairment of insulin action is associated with altered lipid metabolism, obesity, and Type 2 Diabetes. The main aim of this study was to provide further insight into the regulatory mechanisms governing the insulin signaling pathway by investigating the...
Article
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GILZ, a primary target of glucocorticoids, is expressed in human adipocytes, but its importance in adipocyte function is unknown. Because tumor necrosis factor-α (TNFα) is increased in obese adipose tissue and antagonizes a number of glucocorticoid actions, we investigated the interplay of these pathways. GILZ knockdown increased, and GILZ overexpr...
Article
Objective: Growth hormone (GH) administration reduces abdominal, but not lower body, fat mass. To gain insight into the underlying mechanisms, this study examined the expression of the GH receptor (GHR) and some of its targets in abdominal and gluteal adipose tissue. Methods: GHR and GH targets in the lipolytic pathway were assessed (quantitativ...
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The authors issue the following correction in order to cite and discuss previously published in vitro studies on the role of LRP1 that are relevant to this article. The sentence in the Abstract should read “To date, several macrophage receptors have been identified that contribute to the uptake of modified forms of lipoproteins leading to foam cel...
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Objective Adipocytes are robust protein secretors, most notably of adipokines, hormone-like polypeptides, which act in an endocrine and paracrine fashion to affect numerous physiological processes such as energy balance and insulin sensitivity. To understand how such proteins are assembled for secretion we describe the function of a novel endoplasm...
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Early postnatal exposures to sex steroids have been well-recognized to modulate predisposition to diseases of adulthood. There is a complex interplay between timing, duration and dose of endocrine exposures through environmental or dietary sources that may alter the sensitivity of target tissues to the exogenous stimuli. In this study, we determine...
Article
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Within the circulation, cholesterol is transported by lipoprotein particles and is taken up by cells when these particles associate with cellular receptors. In macrophages, excessive lipoprotein particle uptake leads to foam cell formation, which is an early event in the development of atherosclerosis. Currently, mechanisms responsible for foam cel...
Article
Objective To review recent advances in understanding the cellular mechanisms that regulate fat distribution.Methods In this review, new insights into depot and sex differences in the developmental origins and growth of adipose tissues as revealed by studies that use new methods, including lineage tracing, are highlighted.ResultsVariations in fat di...
Article
Premature atherosclerosis is a severe complication of lupus and other systemic autoimmune disorders. Gain-of-function polymorphisms in IFN regulatory factor 5 (IRF5) are associated with an increased risk of developing lupus, and IRF5 deficiency in lupus mouse models ameliorates disease. However, whether IRF5 deficiency also protects against atheros...
Article
Peripheral lower body fat is associated with lower cardiometabolic risk. Physiological differences in gluteal compared with abdominal subcutaneous (sc) adipocyte functions are known but the molecular basis for depot differences in adipocyte function is poorly understood.Objective To identify novel gene regulatory pathways that underlie the heteroge...
Article
International Journal of Obesity is a monthly, multi-disciplinary forum for papers describing basic, clinical and applied studies in biochemistry, genetics and nutrition, together with molecular, metabolic, psychological and epidemiological aspects of obesity and related disorders
Article
Obesity is reaching epidemic proportions so there is growing interest in the mechanisms that regulates adipose tissue development and function. Although murine adipose cell lines are useful for many mechanistic studies, primary human adipose stromal cells (ASCs), which can be isolated from distinct adipose depots and cultured in vitro, have clear t...
Article
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Mice and humans lacking caveolae due to gene knockout or inactivating mutations of cavin-1/PTRF have numerous pathologies including markedly aberrant fuel metabolism, lipodystrophy and muscular dystrophy. We characterized the physiologic/metabolic profile of cavin-1 knockout mice and determined that they were lean due to reduced white adipose depot...
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Background Both the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) are expressed in adipose tissue and assumed to mediate cortisol actions on adipose tissue. The relative significance of the two receptors in mediating glucocorticoid regulation of adipogenesis and adipokine expression in human adipocytes has not been addressed....
Article
Adipose tissue modifies the development of cardiovascular disease in a complex manner: obesity is a major risk factor, especially when accompanied by a central fat distribution. For that reason the characteristics of visceral adipose tissue have attracted most of the research interest thus far, and measurement of waist circumference is now recommen...
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The enterocyte expresses two fatty acid-binding proteins (FABP), intestinal FABP (IFABP; FABP2) and liver FABP (LFABP; FABP1). LFABP is also expressed in liver. Despite ligand transport and binding differences, it has remained uncertain whether these intestinally coexpressed proteins, which both bind long chain fatty acids (FA), are functionally di...
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One of the basic functions of insulin in the body is to inhibit lipolysis in adipocytes. Recently, we have found that insulin inhibits lipolysis and promotes triglyceride storage by decreasing transcription of adipose triglyceride lipase via the mTORC1-mediated pathway (P. Chakrabarti et al., Diabetes 59:775–781, 2010), although the mechanism of th...
Article
Central obesity is associated with insulin resistance and dyslipidemia. Thus, the mechanisms that control fat distribution and its impact on systemic metabolism have importance for understanding risk for diabetes and cardiovascular disease. Hypercortisolemia at the systemic (Cushing's syndrome) or local levels (due to adipose-specific overproductio...
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1,25(OH)(2)D(3) inhibits adipogenesis in mouse 3T3-L1 adipocytes, but little is known about its effects or local metabolism in human adipose tissue. We showed that vitamin D receptor (VDR) and 1α-hydroxylase (CYP27B1), the enzyme that activates 25(OH)D(3) to 1,25(OH)(2)D(3), were expressed in human adipose tissues, primary preadipocytes and newly-d...
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Context: Fat distribution differs in men and women, but in both sexes, a predominantly gluteal-femoral compared with abdominal (central) fat distribution is associated with lower metabolic risk. Differences in cellular characteristics and metabolic functions of these depots have been described, but the molecular mechanisms involved are not underst...
Article
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Obesity, defined as excess fat mass, increases risks for multiple metabolic diseases, such as type 2 diabetes, cardiovascular disease and several types of cancer. Over and above fat mass per se, the pattern of fat distribution, android or truncal as compared to gynoid or peripheral, has a profound influence on systemic metabolism and hence risk for...
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High concentrations of TNF within obese adipose tissue increase basal lipolysis and antagonize insulin signaling. Adipocytes of obese are also exposed to elevated levels glucocorticoids (GCs) which antagonize TNF actions in many cell types. We tested the hypothesis that TNF decreases sensitivity to the antilipolytic effect of insulin and GCs antago...
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Women have more body fat than men, but in contrast to the deleterious metabolic consequences of the central obesity typical of men, the pear-shaped body fat distribution of many women is associated with lower cardiometabolic risk. To understand the mechanisms regulating adiposity and adipose tissue distribution in men and women, significant researc...
Article
Adipose stromal cells proliferate and differentiate into adipocytes, providing a valuable model system for studies of adipocyte biology. We compared differentiation protocols for human preadipocytes and report on their metabolic phenotypes. By simply prolonging the adipogenic induction period from the first 3 to 7 days, the proportion of cells acqu...
Article
Adipose tissue (AT) is no longer considered merely as insulation or padding for human organs. It is an endocrine organ in its own right, which includes composite cells with the ability to differentiate into multiple cell lines. In fact, there is increasing evidence to support the theory that the causation of obesity and its associated metabolic dis...
Chapter
The extrarenal activation of vitamin D (VD) modulates its actions in many tissues. Human fat stores VD and is a target tissue for VD. We found that human adipose tissues as well as preadipocytes expressed all of the enzymes necessary to activate VD [25-hydroxylases (CYP2R1 and CYP27A1) and 1α-hydroxylase (CYP27B1)] as well as the vitamin D receptor...
Article
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Adipose tissue development is tightly regulated by altering gene expression. MicroRNAs are strong posttranscriptional regulators of mammalian differentiation. We hypothesized that microRNAs might influence human adipogenesis by targeting specific adipogenic factors. We identified microRNAs that showed varying abundance during the differentiation of...
Article
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Glucocorticoids (GC) are powerful regulators of adipocyte differentiation, metabolism, and endocrine function and promote the development of upper body obesity, especially visceral fat stores. To provide a comprehensive understanding of how GC affect adipose tissue and adipocyte function, we analyzed patterns of gene expression (HG U95 Affymetrix a...
Article
Recent studies demonstrate that adipose tissue undergoes a continuous process of remodeling that is pathologically accelerated in the obese state. Contrary to earlier dogma, adipocytes die and are replaced by newly differentiated ones. This review will summarize recent advances of our knowledge of the mechanisms that regulate adipose tissue remodel...
Article
IntroductionAdipose Depots: DefinitionsPhysiological and Anatomical Differences among Depots may Drive Functional HeterogeneityHeterogeneity in Adipocyte Function among Adipose DepotsRegional Differences in Adipose Tissue Gene Expression and Protein Production: Relationship to the Metabolic SyndromeSearch for Novel Adipokines with Depot-Specific Ex...
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A sexual dimorphism exists in body fat distribution; females deposit relatively more fat in subcutaneous/inguinal depots whereas males deposit more fat in the intra-abdominal/gonadal depot. Our objective was to systematically document depot- and sex-related differences in the accumulation of adipose tissue and gene expression, comparing differentia...
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High fatty acid (FA) flux is associated with systemic insulin resistance, and African-American (AA) women tend to be more insulin resistant. We assessed possible depot and race difference in the antilipolytic effect of insulin in adipocytes isolated from abdominal (Abd) and gluteal (Glt) subcutaneous (sc) adipose tissue of overweight, postmenopausa...
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This review summarizes recent advances in our understanding of the pre- and posttranscriptional mechanisms that regulate leptin production and secretion in adipocytes. Basal leptin production is proportional to the status of energy stores, i.e., fat cell size, and this is mainly regulated by alterations in leptin mRNA levels. Leptin mRNA levels are...
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Previous studies showed that dietary L-arginine supplementation decreased white fat mass in genetically obese rats. This study tested the effectiveness of L-arginine in diet-induced obesity. Male Sprague-Dawley rats were fed for 15 wk a high-fat (HF) (40% energy) or low-fat (LF) (10% energy) diet beginning at 4 wk of age, resulting in 18% higher bo...
Article
Our main objective was to compare the regulation of cortisol production within omental (Om) and abdominal subcutaneous (Abd sc) human adipose tissue. Om and Abd sc adipose tissue were obtained at surgery from subjects with a wide range of BMI. Hydroxysteroid dehydrogenase (HSD) activity ((3)H-cortisone and (3)H-cortisol interconversion) and express...
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Accumulation of intracellular lipid droplets (LDs) in non-adipose tissues is recognized as a strong prognostic factor for the development of insulin resistance in obesity. LDs are coated with perilipin, adipose differentiation-related protein, tail interacting protein of 47 kd (PAT) proteins that are thought to regulate LD turnover by modulating li...