Visceral fat.

yes

Very good read.

This may be correlated with men who have low test levels and hypogonadism.

Glucocorticoid excess > excess of stress hormone cortisol > accumulation of abdominal fat .

but who is first?

Int J Obes (Lond). 2007 May;31(5):864-70.

Adipocyte-derived products induce the transcription of the StAR promoter and stimulate aldosterone and cortisol secretion from adrenocortical cells through the Wnt-signaling pathway.

Schinner S, Willenberg HS, Krause D, Schott M, Lamounier-Zepter V, Krug AW, Ehrhart-Bornstein M, Bornstein SR, Scherbaum WA.

Department of Endocrinology, Diabetes and Rheumatology, University Hospital D�sseldorf, D�sseldorf, Germany.

CONTEXT: Obesity is associated with hypersecretion of cortisol and aldosterone and a high prevalence of arterial hypertension. At the cellular level, a direct effect of adipocytes on the expression of the steroidogenic acute regulatory (StAR) protein, a regulator of cortisol and aldosterone synthesis, and on aldosterone and cortisol secretion has been shown. However, the molecular mechanisms mediating this effect are not known. OBJECTIVE: Wnt-signaling molecules are secreted by adipocytes and regulate the activity of SF-1, a key transcription factor in adrenal steroidogenesis. Therefore, we investigated whether adipocytes stimulate adrenal steroidogenesis through the activation of Wnt-signaling. RESULTS: Using immunohistochemistry, we detected the expression of frizzled and beta-catenin in the adult human adrenal cortex. Transient transfection of a Wnt-dependent reporter-gene into adrenal NCI-H295R cells showed an induction of Wnt-mediated transcription to 308% after treatment with human fat cell-conditioned medium (FCCM). This finding was paralleled by an induction of StAR promoter activity (420%) by FCCM. The induction of StAR promoter activity by FCCM was inhibited by 49% when Wnt-signaling was blocked by the soluble Wnt-antagonist secreted Frizzled-Related-Protein-1 (sFRP-1). Overexpression of a constitutively active mutant of beta-catenin induced the transcription of the StAR promoter (440%). beta-Catenin and FCCM induced SF-1-mediated transcription at a SF-1-driven reporter gene (420 and 402%, respectively). Furthermore, the secretion of aldosterone and cortisol by NCI-H295R cells induced by FCCM was significantly inhibited by the Wnt-antagonist sFRP-1. CONCLUSION: These data indicate that the Wnt-signaling pathway is one of the mechanisms mediating the effects of fat cells on adrenal StAR transcription and aldosterone and cortisol secretion.

Int J Obes (Lond). 2007 Apr 24.

Human adipocytes induce an ERK1/2 MAP kinases-mediated upregulation of steroidogenic acute regulatory protein (StAR) and an angiotensin II - sensitization in human adrenocortical cells.

Krug AW, Vleugels K, Schinner S, Lamounier-Zepter V, Ziegler CG, Bornstein SR, Ehrhart-Bornstein M.

1Medical Clinic III, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.

Objectives:Hypertension is a major complication of overweight with frequently elevated aldosterone levels in obese patients. Our previous work suggests a direct stimulation of adrenal aldosterone secretion by adipocytes. Owing to aldosterone's important role in maintaining blood pressure homeostasis, its regulation in obesity is of major importance. One objective was to determine the signaling mechanisms involved in adipocyte-induced aldosterone secretion. In addition to a direct stimulation, a sensitization toward angiotensin II (AngII) might be involved. The second objective was to determine a possible adipokines-induced sensitization of human adrenocortical cells to AngII.Design:Human subcutaneous adipocytes and adrenocortical cells, and the adrenocortical cell line NCI-H295R were used. Adrenocortical cells were screened for signal transduction protein expression and phosphorylation. Subsequently, steroidogenic acute regulatory protein (StAR), cAMP response element-binding protein (CREB), cAMP and phosphorylated extracellular regulated kinase were analyzed by Western blot, enzyme-linked immunosorbent assay, quantitative PCR, reporter gene assay and confocal microscopy to investigate their role in adipocyte-mediated aldosterone secretion.Results:AngII-mediated aldosterone secretion was largely increased by preincubating H295R cells with adipocyte secretory products. StAR mRNA and StAR protein were upregulated in a time-dependent way. This steroidogenic effect was independent of the cAMP-protein kinase A (PKA) pathway as cellular cAMP was unaltered and inhibition of PKA by H89 failed to reduce aldosterone secretion. However, CREB reporter gene activity was moderately elevated. Upregulation of StAR was accompanied by ERK1/2 MAP kinase activation and nuclear translocation of the kinases. Inhibition of MAP kinase by UO126 abolished adipokine-stimulated aldosterone secretion from primary human adrenocortical and H295R cells, and inhibited StAR gene activity. Adipokines stimulated steroidogenesis also in primary human adrenocortical cells, supporting a role in human physiology and/or pathology.Conclusions:Adipokines induce aldosterone secretion from human adrenocortical cells and sensitization of the cells to stimulation by AngII, possibly mediated via ERK1/2-dependent upregulation of StAR activity. This stimulation of aldosterone secretion could be one link between overweight and inappropriately elevated aldosterone levels.

Physiol Genomics. 2007 Jun 19;30(1):26-34.

Adrenal transcription regulatory genes modulated by angiotensin II and their role in steroidogenesis.

Romero DG, Rilli S, Plonczynski MW, Yanes LL, Zhou MY, Gomez-Sanchez EP, Gomez-Sanchez CE.

Division of Endocrinology, G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, Mississippi, USA.

Transcription regulatory genes are crucial modulators of cell physiology and metabolism whose intracellular levels are tightly controlled to respond to extracellular stimuli. We studied transcription regulatory genes modulated by angiotensin II, one of the most important regulators of adrenal cortical cell function, and their role in adrenal steroidogenesis in H295R human adrenocortical cells. Angiotensin II-modulated transcription regulatory genes were identified with high-density oligonucleotide microarrays and the results validated by real-time RT-PCR. Cotransfection reporter assays were performed in H295R cells to analyze the role of these transcription regulatory genes in the control of the expression of 11beta-hydroxylase and aldosterone synthase, the last and unique enzymes of the glucocorticoid and mineralocorticoid biosynthetic pathways, respectively. We selected a subset of the most regulated genes for reporter plasmid studies to determine the effect on these enzymes. BHLHB2, BTG2, and SALL1 decreased expression of both enzymes, whereas CITED2, EGR2, ELL2, FOS, FOSB, HDAC5, MAFF, MITF, NFIL3, NR4A1, NR4A2, NR4A3, PER1, and VDR increased expression for both enzymes. By the ratio of aldosterone synthase to 11beta-hydroxylase expression, NFIL3, NR4A1, NR4A2, and NR4A3 show the greatest selectivity toward upregulating expression of the mineralocorticoid biosynthetic pathway preferentially. In summary, this study reports for the first time a set of transcription regulatory genes that are modulated by angiotensin II and their role in adrenal gland steroidogenesis. Abnormal regulation of the mineralocorticoid or glucocorticoid biosynthesis pathways is involved in several pathophysiological conditions; hence the modulated transcription regulatory genes described may correlate with adrenal steroidogenesis pathologies.

Endocr Res. 2004 Nov;30(4):685-93.

Janus kinase 2 signaling in the angiotensin II-dependent activation of StAR expression.

Clark BJ, Li J.

Department of Biochemistry and Molecular Biology, University of Louisville, School of Medicine, Louisville, KY 40292, USA.

Angiotensin II (Ang II)-stimulated aldosterone production in adrenocortical glomerulosa cells requires de novo expression of the steroidogenic acute regulatory protein (StAR). We previously reported that StAR mRNA levels and promoter-reporter gene activity in transiently transfected H295R human adrenocortical cells were stimulated by Ang II and the goals for the current study were to identify signaling pathways activated by Ang II that contribute to StAR transcriptional activation. Using StAR promoter-reporter gene activity and pharmacological inhibition of signaling pathways, we have shown that Ang II-stimulated StAR transcription in H295R cells is dependent upon both influx of external Ca2+ and tyrosine kinase signaling and is enhanced by protein kinase C and mitogen-activated protein kinase (ERK1/2) activation. In particular, Janus tyrosine kinase-2 (Jak2) activation was increased with Ang-II treatment of H295R cells and the select Jak2 inhibitor, AG490, blocked Ang II-dependent Jak2 activation, StAR reporter gene activity, and steroid production. The Ang II-dependent, but not (Bu)2cAMP-dependent, induction of StAR mRNA was also blocked by AG490 and shown to be sensitive to cycloheximide treatment. Together our data support Jak2 as a novel pathway in the Ang II-dependent activation of StAR expression and steroidogenesis in adrenocortical cells and indicate a requirement for ongoing protein synthesis in Ang II-mediated StAR transcription.

J Biol Chem. 2016 Dec 26;278(52):52355-62.

Janus kinase 2 and calcium are required for angiotensin II-dependent activation of steroidogenic acute regulatory protein transcription in H295R human adrenocortical cells.

Li J, Feltzer RE, Dawson KL, Hudson EA, Clark BJ.

Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, Louisville, Kentucky 40292, USA.

Angiotensin II- and K+-stimulated aldosterone production in the adrenocortical glomerulosa cells requires induction of the steroidogenic acute regulatory protein (StAR). While both agents activate Ca2+ signaling, the mechanisms leading to aldosterone synthesis are distinct, and the angiotensin II response cannot be mimicked by K+. We previously reported that StAR mRNA levels and promoter-reporter gene activity in transiently transfected H295R human adrenocortical cells were stimulated by angiotensin II but not by K+ treatment. The current study focused on identifying signaling pathways activated by angiotensin II that contribute to StAR transcriptional activation. We show that the angiotensin II-stimulated transcriptional activation of StAR was dependent upon influx of external calcium and requires protein kinase C activation. Furthermore we describe for the first time that the Janus tyrosine kinase family member, JAK2, was activated by angiotensin II treatment of H295R cells. Treatment of the cells with AG490, a selective inhibitor of JAK2, blocked JAK2 activation and StAR reporter gene activity and inhibited steroid production. Taken together these studies describe a novel pathway controlling StAR expression and steroidogenesis in adrenocortical cells.

Am J Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G923-9.

Adipocytes and preadipocytes promote the proliferation of colon cancer cells in vitro.

Amemori S, Ootani A, Aoki S, Fujise T, Shimoda R, Kakimoto T, Shiraishi R, Sakata Y, Tsunada S, Iwakiri R, Fujimoto K.

Department of Internal Medicine, Saga Medical School, Saga, Japan.

Obesity, a risk factor for colon cancer, is associated with elevated serum levels of leptin, a protein produced by adipocytes. The aim of the present study was to clarify the effects of adipose tissue on colon cancer proliferation by using cultured cell lines. To achieve this, colon cancer cells (CACO-2, T84, and HT29) were cocultured with adipose tissue, isolated mature adipocytes, and isolated preadipocytes in a three-dimensional collagen gel culture system. The adipocytes and preadipocytes used were isolated from C57BL/6J and leptin-deficient ob/ob mice. Proliferation of the cancer cells was evaluated by nuclear bromodeoxyuridine uptake. The adipose tissue, mature adipocytes, and preadipocytes isolated from C57BL/6J mice significantly increased the proliferation of the colon cancer cells. This trophic effect of mature adipocytes on the cancer cell lines was observed only for cells from lean littermates and not for those from ob/ob mice. In contrast, the trophic effect of preadipocytes was not abolished in ob/ob mice, and this finding was supported by the result that leptin had a trophic effect on cancer cells. In conclusion, adipocytes were able to enhance the proliferation of colon cancer cells in vitro, partly via leptin, suggesting that adipose tissues, including mature adipocytes and preadipocytes, may promote the growth of colorectal cancer.

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this thread have to be integrated with:

interesting study
http://www.cuttingedgemuscle.com/Fo...&threadid;=17881

INTEGRATED.

Diabetes. 2007 Feb 7

Visceral fat adipokine secretion is associated with systemic inflammation in obese humans.

Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S.

Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA.

Although excess visceral fat is associated with non-infectious inflammation, it is not clear whether visceral fat is simply associated with, or actually causes metabolic disease in humans. To evaluate the hypothesis that visceral fat promotes systemic inflammation by secreting inflammatory adipokines into the portal circulation that drains visceral fat, we determined adipokine arteriovenous concentration differences across visceral fat, by obtaining portal vein and radial artery blood samples, in 25 extremely obese subjects (body mass index [BMI] 54.7+/-12.6 kg/m(2)) during gastric bypass surgery at Barnes-Jewish Hospital in St.Louis, MO. Mean plasma IL-6 concentration was approximately 50 % greater in portal vein than in radial artery in obese subjects (P=0.007). Portal vein IL-6 concentration correlated directly with systemic C-reactive protein concentrations (r=0.544, p=0.005). Mean plasma leptin concentration was approximately 20% lower in portal vein than in radial artery in obese subjects (P=0.0002). Plasma TNFalpha, resistin, MCP-1, and adiponectin concentrations were similar in portal vein and radial artery in obese subjects. These data suggest that visceral fat is an important site for IL-6 secretion, and provide a potential mechanistic link between visceral fat and systemic inflammation in persons with abdominal obesity.

J Nutr. 2004 Oct;134(10):2673-7.

Expression of interleukin-6 is greater in preadipocytes than in adipocytes of 3t3-L1 cells and C57BL/6J and ob/ob mice.

Harkins JM, Moustaid-Moussa N, Chung YJ, Penner KM, Pestka JJ, North CM, Claycombe KJ.

Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA.

Inflammation plays a major role in the development of chronic diseases such as cardiovascular disease and Type 2 diabetes. Further, it was demonstrated that obese animals and humans have significantly higher levels of circulating proinflammatory cytokines, such as interleukin-6 (IL-6). The aim of this study was to determine whether adipose tissue could be a major source of circulating IL-6 in leptin-deficient obese (ob/ob) mice by comparing the expression of IL-6 in different tissues of ob/ob mice. Our secondary goal was to determine whether preadipocytes are the source of adipose tissue IL-6. The ob/ob mice had higher levels of plasma IL-6 (P < 0.05) and adipose tissue IL-6 mRNA (P < 0.05) compared with lean mice. Interestingly, IL-6 mRNA levels of liver and spleen were not different between ob/ob and lean mice, whereas adipose tissue IL-6 mRNA levels were higher in the ob/ob mice compared with lean mice (P < 0.05). In addition, we showed that IL-6 secretion from the adipose tissue stromal vascular fraction cells was higher than that from fully differentiated adipocytes (P < 0.001). We further demonstrated that 3T3-L1 preadipocytes had significantly higher levels of lipopolysaccharide (LPS)-stimulated IL-6 mRNA and IL-6 secretion than differentiated 3T3-L1 adipocytes. Taken together, these data suggest that adipose tissue and preadipocytes from the adipose tissue stromal vascular fraction may contribute significantly to the increased plasma IL-6 levels in ob/ob mice.

so reduce your visceral fat.

jb

DHEA

1: Eur J Endocrinol. 2006 Oct;155(4):593-600. Links
Effect of DHEA-sulfate on adiponectin gene expression in adipose tissue from different fat depots in morbidly obese humans.Hernandez-Morante JJ, Milagro F, Gabaldon JA, Martinez JA, Zamora S, Garaulet M.
Department of Physiology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain.

OBJECTIVE: A growing body of studies has demonstrated the inverse relationship between DHEA-sulfate (DHEA-S) and the pathological alterations associated with the metabolic syndrome. However, the mechanism by which DHEA-S treatment operates has not been elucidated completely. Adiponectin, an adipose-specific protein, is thought to have anti-diabetic and anti-atherosclerotic properties. Because fat depots differ in the impact of their relationship with the undesirable consequences of obesity, the aim of the present study was to investigate the effect of DHEA-S on adiponectin expression in both s.c. and visceral tissues in a morbidly obese population. DESIGN AND METHODS: We studied the in vitro expression of the adiponectin gene from paired biopsies of human visceral and s.c. adipose tissue, obtained from men and women (body mass index = 48.68+/- 7.43 kg/m2). Adipocytes were incubated for 24 h with or without DHEA-S. Adiponectin mRNA was measured by reverse transcription-quantitative PCR. RESULTS: In this population, DHEA-S plasma values were 141 +/- 105 microg/100 ml. Serum adiponectin values were under normal ranges. In basal conditions, s.c. tissue expressed higher amounts (58%) of adiponectin mRNA than visceral tissue (P = 0.027). Adiponectin expression was differentially regulated in the two depots by DHEA-S. There was a significant increase in adiponectin expression specifically in the visceral tissue (P = 0.020), but no significant effect of DHEA-S on the s.c. tissue (P = 0.738). CONCLUSIONS: In the present study, for the first time in humans, we have shown that DHEA-S treatment is a strong upregulator of adiponectin gene expression in omental adipocytes, suggesting that the positive effects observed by DHEA-S treatment in humans suffering from metabolic syndrome could be exerted through overexpression of adiponectin in the visceral depot.

1: J Endocrinol Invest. 2006 May;29(5):393-8. Links
Dehydroepiandrosterone and human adipose tissue.Sara� F, Yildiz S, Saygili F, Ozgen G, Yilmaz C, Kabalak T, T�z�n M.
Department of Endocrinology and Metabolism, Ege University Hospital, 35100 Izmir, Turkey. [email protected]

OBJECTIVE: The aim of this study was to investigate whether DHEA alters the proliferation and differentiation of human sc and visceral adipose cells in primary cultures. METHOD: Sc and omental adipose tissue was obtained from 10 female donors aged 36+/-3.6 yr with a body mass index (BMI) of 33+/-3.21 kg/m2. Stromal vascular cells were isolated and cultured using modified procedures described by Entenmann and Hauner. For the proliferation assay, stromal-vascular cells from sc and visceral adipose tissue cultures were fed with proliferation media containing 0, 25 or 100 microM DHEA for 3 days. At the end of this treatment period, two type cultures were prepared for determining their metabolic activity using the sulforhodamine B staining procedure. RESULTS: The metabolic activity of proliferating human visceral adipose tissue was higher than sc adipose tissue. The activity of proliferating human visceral tissue cultures decreased more than the sc tissue as the level of DHEA in the cultures was increased. CONCLUSIONS: These data suggest that DHEA predominantly influences the proliferation and differentiation of human omental adipose tissue.

1: JAMA. 2004 Nov 10;292(18):2243-8. Links
Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial.Villareal DT, Holloszy JO.
Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St Louis, Mo 63110, USA.

CONTEXT: Dehydroepiandrosterone (DHEA) administration has been shown to reduce accumulation of abdominal visceral fat and protect against insulin resistance in laboratory animals, but it is not known whether DHEA decreases abdominal obesity in humans. DHEA is widely available as a dietary supplement without a prescription. OBJECTIVE: To determine whether DHEA replacement therapy decreases abdominal fat and improves insulin action in elderly persons. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial conducted in a US university-based research center from June 2001 to February 2004. PARTICIPANTS: Fifty-six elderly persons (28 women and 28 men aged 71 [range, 65-78] years) with age-related decrease in DHEA level. INTERVENTION: Participants were randomly assigned to receive 50 mg/d of DHEA or matching placebo for 6 months. MAIN OUTCOME MEASURES: The primary outcome measures were 6-month change in visceral and subcutaneous abdominal fat measured by magnetic resonance imaging and glucose and insulin responses to an oral glucose tolerance test (OGTT). RESULTS: Of the 56 men and women enrolled, 52 underwent follow-up evaluations. Compliance with the intervention was 97% in the DHEA group and 95% in the placebo group. Based on intention-to-treat analyses, DHEA therapy compared with placebo induced significant decreases in visceral fat area (-13 cm2 vs +3 cm2, respectively; P = .001) and subcutaneous fat (-13 cm2 vs +2 cm2, P = .003). The insulin area under the curve (AUC) during the OGTT was significantly reduced after 6 months of DHEA therapy compared with placebo (-1119 muU/mL per 2 hours vs +818 muU/mL per 2 hours, P = .007). Despite the lower insulin levels, the glucose AUC was unchanged, resulting in a significant increase in an insulin sensitivity index in response to DHEA compared with placebo (+1.4 vs -0.7, P = .005). CONCLUSION: DHEA replacement could play a role in prevention and treatment of the metabolic syndrome associated with abdominal obesity.

i have been touting dhea for many years, chap, available, and effective.

jb

Obesity (Silver Spring). 2006 May;14(5):794-8.

11beta-hydroxysteroid dehydrogenase type 1 mRNA is increased in both visceral and subcutaneous adipose tissue of obese patients.

Desbriere R, Vuaroqueaux V, Achard V, Boullu-Ciocca S, Labuhn M, Dutour A, Grino M.

Service de Gyn�cologie/Obst�trique, CHU Nord, Marseille, France.

OBJECTIVE: Data from rodents provide evidence for a causal role of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) in the development of obesity and its complications. In humans, 11beta-HSD-1 is increased in subcutaneous adipose tissue (SAT) of obese patients, and higher adipose 11beta-HSD-1 was associated with features of the metabolic syndrome. To date, there is no evidence for an increased expression of 11beta-HSD-1 in human visceral adipose tissue (VAT), although VAT is the major predictor for insulin resistance and the metabolic syndrome. RESEARCH METHODS AND PROCEDURES: 11beta-HSD-1 and hexose-6-phosphate dehydrogenase (the enzyme responsible for the synthesis of nicotinamide adenine dinucleotide phosphate, the cofactor required for 11beta-HSD-1 oxoreductase activity) mRNA levels were measured using real-time quantitative reverse transcriptase-polymerase chain reaction in abdominal SAT and VAT biopsies obtained from 10 normal-weight and 12 obese women. Adiponectin mRNA was used as an internal control. RESULTS: 11beta-HSD-1 mRNA concentrations were significantly increased in both SAT and VAT of obese patients (720% and 450% of controls, respectively; p < 0.05) and correlated with hexose-6-phosphate dehydrogenase mRNA levels. The level of VAT 11beta-HSD-1 mRNA correlated with anthropometric parameters: BMI (r = 0.41, p = 0.05), waist circumference (r = 0.44, p = 0.04), abdominal sagittal diameter (r = 0.51, p = 0.02), and percentage fat (r = 0.51, p = 0.02). DISCUSSION: Our results demonstrate for the first time that 11beta-HSD-1 mRNA expression is increased in VAT from obese patients. They strengthen the importance of 11beta-HSD-1 in human obesity and its associated complications and suggest the need of clinical studies with specific 11beta-HSD-1 inhibitors.

Metabolism. 2007 Apr;56(4):533-40.

Regional differences in adipose tissue metabolism in obese men.

Boivin A, Brochu G, Marceau S, Marceau P, Hould FS, Tchernof A.

Molecular Endocrinology and Oncology Research Center, Laval University Medical Research Center and Laval University, Qu�bec, Canada G1V 4G2.

We examined omental and subcutaneous adipose tissue adipocyte size, and lipolysis and lipoprotein lipase (LPL) activity in a sample of 33 men aged 22.6 to 61.2 years and with a body mass index ranging from 24.6 to 79.1 kg/m2. We tested the hypothesis that lipolysis rates would be higher in the omental fat depot than in subcutaneous adipose tissue and that this difference would persist across the spectrum of abdominal adiposity values. Omental and subcutaneous adipose tissue samples were obtained during surgery. Adipocytes were isolated by collagenase digestion. Adipocyte size and LPL activity as well as basal, isoproterenol-, forskolin-, and dibutyryl cyclic adenosine monophosphate-stimulated lipolysis were measured. Although adipocytes from both fat compartments were larger in obese subjects, no difference was observed in the size of omental vs subcutaneous fat cells. Lipoprotein lipase activity, expressed as a function of cell number, was significantly higher in omental than in subcutaneous fat tissue (P<.005). Basal lipolysis and lipolytic responses to isoproterenol, forskolin, or dibutyryl cyclic adenosine monophosphate, expressed either as a function of cell number or as a fold response over basal levels, were not significantly different in omental vs subcutaneous fat cells. When stratifying the sample in tertiles of waist circumference, adipocyte diameter was similar in the omental and subcutaneous depots for all adiposity values. Omental adipocyte size reached a plateau in the 2 upper tertiles of waist circumference, that is, from a waist circumference of 125 cm and above. Lipoprotein lipase activity was significantly higher in omental cells.

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FAT/CD36 and FATP4 (fat transport proteins).
overexpression and fat uptake upregulation:
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Diabetes. 2007 May;56(5):1369-75.

Direct free fatty acid uptake into human adipocytes in vivo: relation to body fat distribution.

Shadid S, Koutsari C, Jensen MD.

Endocrine Research Unit, Mayo Clinic, Rochester, MN 55905, USA.

Int J Obes (Lond). 2006 Jun;30(6):877-83.

The fatty acid transporter FAT/CD36 is upregulated in subcutaneous and visceral adipose tissues in human obesity and type 2 diabetes.

Bonen A, Tandon NN, Glatz JF, Luiken JJ, Heigenhauser GJ.

Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.

Am J Physiol Endocrinol Metab. 2006 Jan;290(1):E87-E91.

Differences in transport of fatty acids and expression of fatty acid transporting proteins in adipose tissue of obese black and white women.

Bower JF, Davis JM, Hao E, Barakat HA.

Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.

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it seems a problem more of size than of number of cells (in visceral obesity).
cos:
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Obesity (Silver Spring). 2007 May;15(5):1155-63.

Omental 11beta-hydroxysteroid dehydrogenase 1 correlates with fat cell size independently of obesity.

Michailidou Z, Jensen MD, Dumesic DA, Chapman KE, Seckl JR, Walker BR, Morton NM.

Endocrinology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.

OBJECTIVES: In ideopathic obesity, there is evidence that enhanced cortisol regeneration within abdominal subcutaneous adipose tissue may contribute to adiposity and metabolic disease. Whether the cortisol regenerating enzyme, 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), or glucocorticoid receptor (GRalpha) levels are altered in other adipose depots remains uncertain. Our objective was to determine the association between 11betaHSD1 and GRalpha mRNA levels in four distinct adipose depots and measures of obesity and the metabolic syndrome. RESEARCH METHODS AND PROCEDURES: Adipose tissue biopsies were collected from subcutaneous (abdominal, thigh, gluteal) and intra-abdominal (omental) adipose depots from 21 women. 11betaHSD1 and GRalpha mRNA levels were measured by real-time polymerase chain reaction. Body composition, fat distribution, fat cell size, and blood lipid, glucose, and insulin levels were measured. RESULTS: 11betaHSD1 mRNA was highest in abdominal subcutaneous (p < 0.001) and omental (p < 0.001) depots and was positively correlated with BMI and visceral adiposity in all depots. Omental 11betaHSD1 correlated with percent body fat (R = 0.462, p < 0.05), fat cell size (R = 0.72, p < 0.001), and plasma triglycerides (R = 0.46, p < 0.05). Conversely, GRalpha mRNA was highest in omental fat (p < 0.001). GRalpha mRNA was negatively correlated with BMI in the abdominal subcutaneous (R = -0.589, p < 0.05) and omental depots (R = -0.627, p < 0.05). Omental GRalpha mRNA was inversely associated with visceral adiposity (R = -0.507, p < 0.05), fat cell size (R = -0.52, p < 0.01), and triglycerides (R = -0.50, p < 0.05). DISCUSSION: Obesity was associated with elevated 11betaHSD1 mRNA in all adipose compartments. GRalpha mRNA is reduced in the omental depot with obesity. The novel correlation of 11betaHSD1 with omental fat cell size, independent of obesity, suggests that intracellular cortisol regeneration is a strong predictor of hypertrophy in the omentum.

Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E267-77.

Abundance of two human preadipocyte subtypes with distinct capacities for replication, adipogenesis, and apoptosis varies among fat depots.

Tchkonia T, Tchoukalova YD, Giorgadze N, Pirtskhalava T, Karagiannides I, Forse RA, Koo A, Stevenson M, Chinnappan D, Cartwright A, Jensen MD, Kirkland JL.

Evans Department of Medicine, Boston University Medical Center, Boston, MA 02118, USA.

Fat depots vary in function and size. The preadipocytes that fat cells develop from exhibit distinct regional characteristics that persist in culture. Human abdominal subcutaneous cultured preadipocytes undergo more extensive lipid accumulation, higher adipogenic transcription factor expression, and less TNF-alpha-induced apoptosis than omental preadipocytes. We found higher replicative potential in subcutaneous and mesenteric than in omental preadipocytes. In studies of colonies arising from single preadipocytes, two preadipocyte subtypes were found, one capable of more extensive replication, differentiation, and adipogenic transcription factor expression and less apoptosis in response to TNF-alpha than the other. The former was more abundant in subcutaneous and mesenteric than in omental preadipocyte populations, potentially contributing to regional variation in replication, differentiation, and apoptosis. Both subtypes were found in strains derived from single human preadipocytes stably expressing telomerase, confirming that both subtypes are of preadipocyte lineage. After subcloning of cells of either subtype, both subtypes were found, indicating that switching can occur between subtypes. Thus proportions of preadipocyte subtypes with distinct cell-dynamic properties vary among depots, potentially permitting tissue plasticity through subtype selection during development.

Int J Obes (Lond). 2006 Jun;30(6):899-905.

Relationship between fat cell size and number and fatty acid composition in adipose tissue from different fat depots in overweight/obese humans.

Garaulet M, Hernandez-Morante JJ, Lujan J, Tebar FJ, Zamora S.

Department of Physiology, University of Murcia, Murcia, Spain.

FASEB J. 2006 Jul;20(9):1540-2.

Separation of human adipocytes by size: hypertrophic fat cells display distinct gene expression.

Jern�s M, Palming J, Sj�holm K, Jennische E, Svensson PA, Gabrielsson BG, Levin M, Sj�gren A, Rudemo M, Lystig TC, Carlsson B, Carlsson LM, L�nn M.

Research Centre for Endocrinology and Metabolism, Division of Body Composition and Metabolism, Department of Internal Medicine, Vita Str�ket 15, SE 413 45 G�teborg, Sweden.

Enlarged adipocytes are associated with insulin resistance and are an independent predictor of type 2 diabetes. To understand the molecular link between these diseases and adipocyte hypertrophy, we developed a technique to separate human adipocytes from an adipose tissue sample into populations of small cells (mean 57.6+/-3.54 microm) and large cells (mean 100.1+/-3.94 microm). Microarray analysis of the cell populations separated from adipose tissue from three subjects identified 14 genes, of which five immune-related, with more than fourfold higher expression in large cells than small cells. Two of these genes were serum amyloid A (SAA) and transmembrane 4 L six family member 1 (TM4SF1). Real-time RT-PCR analysis of SAA and TM4SF1 expression in adipocytes from seven subjects revealed 19-fold and 22-fold higher expression in the large cells, respectively, and a correlation between adipocyte size and both SAA and TM4SF1 expression. The results were verified using immunohistochemistry. In comparison with 17 other human tissues and cell types by microarray, large adipocytes displayed by far the highest SAA and TM4SF1 expression. Thus, we have identified genes with markedly higher expression in large, compared with small, human adipocytes.

J Clin Endocrinol Metab. 2005 Apr;90(4):2233-9.

A microarray search for genes predominantly expressed in human omental adipocytes: adipose tissue as a major production site of serum amyloid A.

Sj�holm K, Palming J, Olofsson LE, Gummesson A, Svensson PA, Lystig TC, Jennische E, Brandberg J, Torgerson JS, Carlsson B, Carlsson LM.

Research Centre for Endocrinology and Metabolism, Vita Str�ket 12, Sahlgrenska University Hospital, SE-413 45 G�teborg, Sweden. kajsa.

To identify genes predominantly expressed in omental adipocytes, microarray expression profiles from 33 human tissues or cell types were analyzed, using an algorithm developed for identification of transcripts predominantly expressed in a certain tissue. Both known adipocyte-specific and more unexpected genes were among the 28 genes identified. To validate the approach, adipocyte expression of three of these genes, acute-phase serum amyloid A (A-SAA), aquaporin 7, and transport secretion protein-2.2, was compared with 17 other human tissues by real-time PCR. The unexpectedly high expression of A-SAA in adipocytes was further verified by Northern blot and immunohistochemistry. The liver, reported to be the main production site for A-SAA, displayed the second highest expression using microarray and real-time PCR. In obese subjects, adipose tissue mRNA and serum A-SAA levels were down-regulated during an 18-wk diet regime (P < 0.05 and P < 0.0001, respectively). A-SAA serum levels were highly correlated to adipose tissue mRNA levels (P < 0.001) and to the total (P < 0.0001) and sc (P < 0.0001) adipose tissue areas, as analyzed by computed tomography. We show that adipose tissue is a major expression site of A-SAA during the nonacute-phase reaction condition. This provides a direct link between adipose tissue mass and a marker for low-grade inflammation and cardiovascular risk.

so will fluoxymesterone, being an anti-glucocorticoid, increase the possibility of buring viceral fat? I hope so as I'm using it right now as a cutter...

in principle, yes.