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Other Original Articles: Ilana Harman-Boehm, Matthias Blüher, Henry Redel, Netta Sion-Vardy, Shira Ovadia, Eliezer Avinoach, Iris Shai, Nora Klöting, Michael Stumvoll, Nava Bashan, and Assaf Rudich Macrophage Infiltration into Omental Versus Subcutaneous Fat across Different Populations: Effect of Regional Adiposity and the Comorbidities of Obesity J Clin Endocrinol Metab 2007; 92: 2240-2247 [Abstract] [Full text] [PDF]

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Re: “Fat” adipocytes and physical forces

Assaf Rudich, Ilana Harman-Boehm, Matthias Blüher, Nava Bashan   (27 May 2008)

“Fat” adipocytes and physical forces

Isabel Azevedo, Rosário Monteiro, Conceição Calhau   (30 April 2008)

Re: “Fat” adipocytes and physical forces 27 May 2008
Assaf Rudich, Researcher Ben-Gurion University, Beer-Sheva, Israel, Ilana Harman-Boehm, Matthias Blüher, Nava Bashan Send letter to journal: Re: Re: “Fat” adipocytes and physical forces rudich{at}bgu.ac.il Assaf Rudich, et al.	In their recent E-letter, Azevedo et al. raise the intriguing proposition that increased physical forces, such as increased intra-abdominal pressure, coupled with adipocyte hypertrophy, could constitute a mechanism for adipocyte rupture. This, in turn, could lead to the preferential macrophage infiltration seen in intra-abdominal versus subcutaneous fat. In our study, we observed higher expression of the macrophage marker CD68 in omental fat also in the lean state, suggesting that "intrinsic characteristics" of adipose tissue from different depots, likely unrelated to cell hypertrophy, contribute to macrophage infiltration. In addition, it is indeed reasonable to assume that larger adipocytes are more fragile, and hence, more sensitive to physical forces, consistent with the mathematical modeling used by Azevedo and co-workers (1). However, though evidence exists for increased intra-abdominal pressure in morbid obesity, it is not known whether subcutaneous adipocytes are subjected to fewer or less intense physical insults than intra-abdominal fat cells. Furthermore, we found that the mean diameter of omental adipocytes is 10% smaller (P < 0.001 by paired t-test), rather than larger, than subcutaneous adipocytes. Other groups also reported that omental adipocytes were of similar size or smaller than subcutaneous adipocytes (2, 3). The seemingly counter-intuitive observation that omental adipocytes are not larger than subcutaneous adipocytes does not rule out a role for fat cell hypertrophy in the pathogenesis of fat tissue inflammation. Very recently, it has been proposed that in humans total adipocyte number is closely maintained in adulthood in both lean and obese states (4), suggesting that adult-onset increase in fat mass is largely attributable to increased fat cell volume. In rodents, intra-abdominal fat mass tends to grow with a predominantly hypertrophic response, whereas subcutaneous fat does so with hyperplasia (5). Consistently, a larger difference in adipocyte size was observed between lean and obese persons in omental adipocytes than in subcutaneous adipocytes (3). Hence, it is possible that omental and subcutaneous adipocytes are programmed to maintain different cell sizes and respond differentially to excess energy. Perhaps it is the rate of size change occurring in obesity, rather than the absolute size, that confers increased vulnerability to cell death--whether related to physical forces or not—and contributed to intra-abdominal adipose tissue inflammation. References 1. Monteiro R, de Castro PM, Calhau C, Azevedo I 2006 Adipocyte size and liability to cell death. Obes Surg 16:804-806 2. Tchernof A, Belanger C, Morisset AS, Richard C, Mailloux J, Laberge P, Dupont P 2006 Regional differences in adipose tissue metabolism in women: minor effect of obesity and body fat distribution. Diabetes 55:1353-1360 3. Winkler G, Kiss S, Keszthelyi L, Sapi Z, Ory I, Salamon F, Kovacs M, Vargha P, Szekeres O, Speer G, Karadi I, Sikter M, Kaszas E, Dworak O, Gero G, Cseh K 2003 Expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tissue in correlation with adipocyte cell volume, serum TNF-alpha, soluble serum TNF-receptor-2 concentrations and C-peptide level. Eur J Endocrinol 149:129-135 4. Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Naslund E, Britton T, Concha H, Hassan M, Ryden M, Frisen J, Arner P 2008 Dynamics of fat cell turnover in humans. Nature doi: 10.1038/nature06902, Letters to Editor 5. DiGirolamo M, Fine JB, Tagra K, Rossmanith R 1998 Qualitative regional differences in adipose tissue growth and cellularity in male Wistar rats fed ad libitum. Am J Physiol 274:R1460-R1467
“Fat” adipocytes and physical forces 30 April 2008
Isabel Azevedo Department of Biochemistry (U38/FCT), Faculty of Medicine, University of Porto, Rosário Monteiro, Conceição Calhau Send letter to journal: Re: “Fat” adipocytes and physical forces isabelaz{at}med.up.pt Isabel Azevedo, et al.	In their recent article on the two main types of accumulated fat distribution in human obesity and correspondent pathogenicity (1), Harman-Boehm et al. point out that “preferential macrophage infiltration into omental fat is a general phenomenon exaggerated by central obesity, potentially linking central adiposity with increased risk of diabetes and coronary heart disease”. They verified that across a large range of accumulated fat, from lean to severely obese subjects, that omental fat always had more infiltrated macrophages than subcutaneous fat in the same subject. The macrophage accumulating effect was exaggerated by obesity, particularly if predominantly intra-abdominal. Moreover, and as expected, the number of omental macrophages was associated with the number of metabolic syndrome parameters, including impaired glucose homeostasis. The reported parallel increase in inflammatory cytokine expression is justifiably presumed to link central obesity and metabolic and cardiac risk, but a mechanism for that connection is not proposed. We believe it is relevant that macrophages surround dead adipocytes in adipose tissue (2). We recently reported that large adipocytes rupture, for purely physical reasons (3), generating an inflammatory reaction. Moreover, intra-abdominal and intra-thoracic acute pressure variations, for example, with cough, physical exercise and even obstructive sleep apnoea (4), further strain visceral fat adipocytes, and may explain, in part, the special pathogenicity of visceral fat accumulation. References 1. Harman-Boehm I, Blüher M, Redel H. Sion-Vardy N, Ovadia S, Avinoach E, Shai I, Klöting N, Stumvoll M, Bashan N, Rudich A 2007 Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J Clin Endocrinol Metab 92:2240-2247 2. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Wang S, Fortier M, Greenberg AS, Obin MS 2005 Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lip Res 46:2347-2355 3. Monteiro R, Calhau C, Azevedo I 2006 Adipocyte size and liability to cell death. Obes Surg 16:804-806 4. Monteiro R, Calhau C, Azevedo I 2007 Obstructive sleep apnoea and adipocyte death. Eur J Heart Fail 9:103-104