The relationship of omental and subcutaneous adipocyte size to metabolic disease in severe obesity

Jean O'Connell, Lydia Lynch, Tom J Cawood, Anna Kwasnik, Niamh Nolan, Justin Geoghegan, Aiden McCormick, Cliona O'Farrelly, Donal O'Shea, Jean O'Connell, Lydia Lynch, Tom J Cawood, Anna Kwasnik, Niamh Nolan, Justin Geoghegan, Aiden McCormick, Cliona O'Farrelly, Donal O'Shea

Abstract

Objective: Several studies have reported the existence of a subgroup of obese individuals with normal metabolic profiles. It remains unclear what factors are responsible for this phenomenon. We proposed that adipocyte size might be a key factor in the protection of metabolically healthy obese (MHO) individuals from the adverse effects of obesity.

Subjects: Thirty-five patients undergoing bariatric surgery were classified as MHO (n = 15) or metabolically unhealthy obese (MUO, n = 20) according to cut-off points adapted from the International Diabetes Federation definition of the metabolic syndrome. Median body mass index (BMI) was 48 (range 40-71).

Results: There was a moderate correlation between omental adipocyte size and subcutaneous adipocyte size (r = 0.59, p<0.05). The MHO group had significantly lower mean omental adipocyte size (80.9+/-10.9 microm) when compared with metabolically unhealthy patients (100.0+/-7.6 microm, p<0.0001). Mean subcutaneous adipocyte size was similar between the two groups (104.1+/-8.5 microm versus 107.9+/-7.1 microm). Omental, but not subcutaneous adipocyte size, correlated with the degree of insulin resistance as measured by HOMA-IR (r = 0.73, p<0.0005), as well as other metabolic parameters including triglyceride/HDL-cholesterol ratio and HbA1c. Twenty-eight patients consented to liver biopsy. Of these, 46% had steatohepatitis and fibrosis. Fifty percent (including all the MHO patients) had steatosis only. Both omental and subcutaneous adipocyte size were significantly associated with the degree of steatosis (r = 0.66, p<0.0001 and r = 0.63, p<0.005 respectively). However, only omental adipocyte size was an independent predictor of the presence or absence of fibrosis.

Conclusion: Metabolically healthy individuals are a distinct subgroup of the severely obese. Both subcutaneous and omental adipocyte size correlated positively with the degree of fatty liver, but only omental adipocyte size was related to metabolic health, and possibly progression from hepatic steatosis to fibrosis.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Adipocyte size results (micrometers) for…
Figure 1. Adipocyte size results (micrometers) for Method I and Method II.
Figure 2. Adipocyte size in obese subjects…
Figure 2. Adipocyte size in obese subjects grouped by metabolic profile.
Metabolically healthy obese  =  MHO, metabolically unhealthy obese  =  MUO, metabolically unhealthy obese patients with Type 2 Diabetes  =  DM2. Mean omental adipocyte diameter (represented by the horizontal lines) was 80.9±10.9 µm in MHO, 98.2±10.2 µm in MUO, and 104.3+/−4.2 µm in DM2. Mean subcutaneous diameter was 104.1±8.5 µm in MHO, 104.9±5.0 µm in MUO, and 113.2±6.9 µm in DM2.
Figure 3. Correlations of adipocyte size with…
Figure 3. Correlations of adipocyte size with metabolic parameters.
Omental adipocyte size (A, B and C) and subcutaneous adipocyte size (D, E and F) correlated with the degree of insulin resistance as measured by HOMA-IR, the TGL/HDL ratio, and the degree of hepatic steatosis. X  =  MHO, • =  MUO, ○ =  DM2
Figure 4. Omental adipocyte size, metabolic parameters…
Figure 4. Omental adipocyte size, metabolic parameters and hepatic fibrosis.
A) Omental and subcutaneous adipocyte size, B) TGL/HDL and HOMA-IR ratios and C) Age, BMI and degree of steatosis, in subjects with hepatic steatosis alone, compared with subjects with evidence of hepatic fibrosis (** p

References

    1. Andres R. Effect of obesity on total mortality. Int J Obes. 1980;4:381–386.
    1. Ruderman NB, Schneider SH, Berchtold P. The “metabolically-obese,” normal-weight individual. Am J Clin Nutr. 1981;34:1617–1621.
    1. Iacobellis G, Ribaudo MC, Zappaterreno A, Iannucci CV, Leonetti F. Prevalence of uncomplicated obesity in an Italian obese population. Obes Res. 2005;13:1116–1122.
    1. Brochu M, Tchernof A, Dionne IJ, Sites CK, Eltabbakh GH, et al. What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women? J Clin Endocrinol Metab. 2001;86:1020–1025.
    1. Stefan N, Kantartzis K, Machann J, Schick F, Thamer C, et al. Identification and characterization of metabolically benign obesity in humans. Arch Intern Med. 2008;168:1609–1616.
    1. Karelis AD, Faraj M, Bastard JP, St-Pierre DH, Brochu M, et al. The metabolically healthy but obese individual presents a favorable inflammation profile. J Clin Endocrinol Metab. 2005;90:4145–4150.
    1. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89:2548–2556.
    1. Scherer PE. Adipose tissue: from lipid storage compartment to endocrine organ. Diabetes. 2006;55:1537–1545.
    1. Salans LB, Knittle JL, Hirsch J. The role of adipose cell size and adipose tissue insulin sensitivity in the carbohydrate intolerance of human obesity. J Clin Invest. 1968;47:153–165.
    1. Jernas M, Palming J, Sjoholm K, Jennische E, Svensson PA, et al. Separation of human adipocytes by size: hypertrophic fat cells display distinct gene expression. FASEB J. 2006;20:1540–1542.
    1. Franck N, Stenkula KG, Ost A, Lindstrom T, Stralfors P, et al. Insulin-induced GLUT4 translocation to the plasma membrane is blunted in large compared with small primary fat cells isolated from the same individual. Diabetologia. 2007;50:1716–1722.
    1. Skurk T, Alberti-Huber C, Herder C, Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab. 2007;92:1023–1033.
    1. Yang X, Smith U. Adipose tissue distribution and risk of metabolic disease: does thiazolidinedione-induced adipose tissue redistribution provide a clue to the answer? Diabetologia. 2007;50:1127–1139.
    1. Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev. 2000;21:697–738.
    1. Rasmussen MS, Lihn AS, Pedersen SB, Bruun JM, Rasmussen M, et al. Adiponectin receptors in human adipose tissue: effects of obesity, weight loss, and fat depots. Obesity (Silver Spring) 2006;14:28–35.
    1. Drolet R, Belanger C, Fortier M, Huot C, Mailloux J, et al. Fat depot-specific impact of visceral obesity on adipocyte adiponectin release in women. Obesity (Silver Spring) 2009;17:424–430.
    1. Kotronen A, Westerbacka J, Bergholm R, Pietilainen KH, Yki-Jarvinen H. Liver fat in the metabolic syndrome. J Clin Endocrinol Metab. 2007;92:3490–3497.
    1. Kim CH, Younossi ZM. Nonalcoholic fatty liver disease: a manifestation of the metabolic syndrome. Cleve Clin J Med. 2008;75:721–728.
    1. Sturm R. Increases in clinically severe obesity in the United States, 1986-2000. Arch Intern Med. 2003;163:2146–2148.
    1. McLaughlin T, Reaven G, Abbasi F, Lamendola C, Saad M, et al. Is there a simple way to identify insulin-resistant individuals at increased risk of cardiovascular disease? Am J Cardiol. 2005;96:399–404.
    1. Hubscher SG. Histological assessment of non-alcoholic fatty liver disease. Histopathology. 2006;49:450–465.
    1. Unger RH. Lipid overload and overflow: metabolic trauma and the metabolic syndrome. Trends Endocrinol Metab. 2003;14:398–403.
    1. Sniderman AD, Bhopal R, Prabhakaran D, Sarrafzadegan N, Tchernof A. Why might South Asians be so susceptible to central obesity and its atherogenic consequences? The adipose tissue overflow hypothesis. Int J Epidemiol. 2007;36:220–225.
    1. Jacobsson B, Smith U. Effect of cell size on lipolysis and antilipolytic action of insulin in human fat cells. J Lipid Res. 1972;13:651–656.
    1. Lonn M, Mehlig K, Bengtsson C, Lissner L. Adipocyte size predicts incidence of type 2 diabetes in women. FASEB J 2009
    1. Weyer C, Foley JE, Bogardus C, Tataranni PA, Pratley RE. Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance. Diabetologia. 2000;43:1498–1506.
    1. Bays HE, Gonzalez-Campoy JM, Bray GA, Kitabchi AE, Bergman DA, et al. Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity. Expert Rev Cardiovasc Ther. 2008;6:343–368.
    1. Heilbronn L, Smith SR, Ravussin E. Failure of fat cell proliferation, mitochondrial function and fat oxidation results in ectopic fat storage, insulin resistance and type II diabetes mellitus. Int J Obes Relat Metab Disord. 2004;28(Suppl 4):S12–21.
    1. Arner E, Westermark PO, Spalding KL, Britton T, Ryden M, et al. Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes. 59:105–109.
    1. Votruba SB, Jensen MD. Sex differences in abdominal, gluteal, and thigh LPL activity. Am J Physiol Endocrinol Metab. 2007;292:E1823–1828.
    1. Tchoukalova YD, Koutsari C, Karpyak MV, Votruba SB, Wendland E, et al. Subcutaneous adipocyte size and body fat distribution. Am J Clin Nutr. 2008;87:56–63.
    1. Jensen MD, Johnson CM. Contribution of leg and splanchnic free fatty acid (FFA) kinetics to postabsorptive FFA flux in men and women. Metabolism. 1996;45:662–666.
    1. Shen W, Wang Z, Punyanita M, Lei J, Sinav A, et al. Adipose tissue quantification by imaging methods: a proposed classification. Obes Res. 2003;11:5–16.
    1. Yang YK, Chen M, Clements RH, Abrams GA, Aprahamian CJ, et al. Human mesenteric adipose tissue plays unique role versus subcutaneous and omental fat in obesity related diabetes. Cell Physiol Biochem. 2008;22:531–538.
    1. Tchkonia T, Tchoukalova YD, Giorgadze N, Pirtskhalava T, Karagiannides I, et al. Abundance of two human preadipocyte subtypes with distinct capacities for replication, adipogenesis, and apoptosis varies among fat depots. Am J Physiol Endocrinol Metab. 2005;288:E267–277.
    1. Li H, Lelliott C, Hakansson P, Ploj K, Tuneld A, et al. Intestinal, adipose, and liver inflammation in diet-induced obese mice. Metabolism. 2008;57:1704–1710.
    1. Imbeault P, Lemieux S, Prud'homme D, Tremblay A, Nadeau A, et al. Relationship of visceral adipose tissue to metabolic risk factors for coronary heart disease: is there a contribution of subcutaneous fat cell hypertrophy? Metabolism. 1999;48:355–362.
    1. Blaak E. Gender differences in fat metabolism. Curr Opin Clin Nutr Metab Care. 2001;4:499–502.
    1. Youssef WI, McCullough AJ. Steatohepatitis in obese individuals. Best Pract Res Clin Gastroenterol. 2002;16:733–747.
    1. Palekar NA, Naus R, Larson SP, Ward J, Harrison SA. Clinical model for distinguishing nonalcoholic steatohepatitis from simple steatosis in patients with nonalcoholic fatty liver disease. Liver Int. 2006;26:151–156.
    1. Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 1999;30:1356–1362.
    1. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112:1796–1808.
    1. Cancello R, Tordjman J, Poitou C, Guilhem G, Bouillot JL, et al. Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity. Diabetes. 2006;55:1554–1561.
    1. Tordjman J, Poitou C, Hugol D, Bouillot JL, Basdevant A, et al. Association between omental adipose tissue macrophages and liver histopathology in morbid obesity: influence of glycemic status. J Hepatol. 2009;51:354–362.
    1. Winkler G, Kiss S, Keszthelyi L, Sapi Z, Ory I, et al. 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. 2003;149:129–135.
    1. Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology. 1998;114:842–845.

Source: PubMed

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