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Central obesity as a clinical marker of adiposopathy; increased visceral adiposity as a surrogate marker for global fat dysfunction

Bays, Harold

Current Opinion in Endocrinology & Diabetes and Obesity: October 2014 - Volume 21 - Issue 5 - p 345–351
doi: 10.1097/MED.0000000000000093
OBESITY AND NUTRITION: Edited by Caroline Apovian

Purpose of review Subcutaneous adipose tissue (SAT) is often described as ‘protective’. Visceral adipose tissue (VAT) is often described as ‘pathologic’. However, both SAT and VAT have protective and pathologic potential, with interdependent biologic functions.

Recent findings Most of the body's (excess) energy is stored as fat in SAT. If during positive caloric balance, SAT does not undergo adequate adipogenesis, then excess energy may result in adipocyte hypertrophy, leading to hypoxia, immunopathies, and endocrinopathies. Energy overflow may promote accumulation of pericardial fat, perivascular fat, and myocardial fat, which may directly contribute to atherosclerotic cardiovascular disease (CVD). Lipotoxic free fatty acid delivery to nonadipose body organs (e.g. liver, muscle, and pancreas) may indirectly contribute to CVD by promoting the most common metabolic disorders encountered in clinical practice (e.g. high blood sugars, high blood pressure, and dyslipidaemia), all major CVD risk factors. Finally, SAT energy overflow may increase VAT accumulation, which is also associated with increased risk of metabolic diseases and CVD.

Summary Increased VAT is a surrogate marker for SAT dysfunction which increases waist circumference, reflecting a shared pathologic process leading to the pathogenic fat accumulation of other fat depots and fatty infiltration of nonadipose body organs. Central obesity is a clinical marker for adiposopathy.

Louisville Metabolic and Atherosclerosis Research Center, Louisville, Kentucky, USA

Correspondence to Harold Bays, MD, FTOS, FACC, FACE, FNLA, L-MARC Research Center, 3288 Illinois Avenue, Louisville KY 40213, USA. Tel: +1 502 515 5672; fax: +1 502 214 3999; e-mail:; website:

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

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Adiposopathy (‘sick fat’) is defined as adipose tissue dysfunction promoted by positive caloric balance and sedentary lifestyle in genetically and environmentally susceptible individuals. Anatomically, adiposopathy is classically characterized by adipocyte hypertrophy and visceral fat accumulation [1] (see Fig. 1). Pathophysiologically, adiposopathy is manifest by adipocyte and adipose tissue endocrine and immune disorders that contribute to metabolic diseases and increased risk of cardiovascular disease (CVD) [1] (see Fig. 1).



Box 1

Box 1

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SAT and VAT are often described as two intrinsically different organs, with different genetic lineages, whose accumulation promotes different, if not opposing health consequences [7]. Peripheral SAT is often described as ‘protective’ [8]. VAT is often described as ‘pathologic’ (i.e. a ‘unique pathogenic fat depot’) [9]. However, both SAT and VAT have ‘protective’ and ‘pathologic’ properties.

In addition to storing fuel in the form of lipids, adipose tissue produces hormones and immune factors [2]. These functions may be ‘protective’ during periods of starvation, as well as potentially protective against endocrine and infectious provocations which might otherwise contribute to ill-health (e.g. SAT may protect against superficial skin wounds) [10]. Both SAT and VAT provide physical padding and insulation [10], which may provide musculoskeletal and thermal protection. VAT may provide physical protection against mechanical intraorgan damage (e.g. trauma or other forces that might otherwise jar the abdomen) and may protect against peritoneal catastrophes (e.g. perforated visceral organs) [10].

During positive caloric balance, SAT accumulation may also be metabolically ‘protective’ if adipocyte proliferation and differentiation provides a sufficient number of functional fat cells to mitigate adiposopathy (e.g. ‘sick fat disease’) [11▪,12]. This ‘protects’ against the adverse metabolic consequences of positive caloric balance, otherwise leading to adiposopathic endocrinopathies, inflammation, and lipotoxic energy overflow to other fat depots and body organs (i.e. via increased circulating free fatty acids [1,13–16]). However, if SAT is to be truly ‘protective’, then the increase in SAT mass cannot be of such magnitude as to cause ‘fat mass disease’, defined as abnormal biomechanical physical forces that cause pathogenic stresses on weight bearing joints, immobility, tissue compressions, and tissue friction [11▪]. Thus, during positive caloric balance, SAT might be considered truly ‘protective’ only when sufficient functional adipocytes are made available to avoid sick fat disease, whereas at the same time, the amount of adipose tissue is not sufficient to cause fat mass disease. Such a balanced SAT response to positive caloric balance may help explain populations described as ‘metabolically healthy, but obese’ [11▪,17]. Although this scenario is intriguing, it is likely to be the rare exception because amongst most individuals who are overweight or obese, SAT usually contributes to some form of sick fat disease (adiposopathy) and fat mass disease [1,18]. In fact, some have questioned the degree by which ‘metabolically healthy, but obese’ populations actually exist [19▪,20▪].

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From an organ standpoint, SAT, VAT, and other fat depots are globally increased during positive caloric balance [8]. From a cellular standpoint, adipocyte size may be globally regulated, independent of the variations in body fat distribution [21]. This supports the interconnectivity and interdependency of body fat depots and adipocytes, wherein adipose tissue's pathogenic potential might best be based upon the global assessments of adipose tissue function or dysfunction, rather than assigning the binary ‘protective’ and ‘pathologic’ labelling, depot-by-depot, adipocyte-by-adipocyte.

At least since the 1920s, central obesity and increased VAT accumulation were known to correlate with metabolic diseases and increased CVD risk [22▪]. Within the national and international metabolic syndrome definitions, central obesity is the only anatomic diagnostic criterion (with the other criteria being high blood sugar, high blood pressure, and dyslipidaemia) [22▪]. When these clinical findings are coupled with the observations that SAT and VAT differ in genetic origins, cellular composition, physiology, endocrinology, immunology, innervation, blood flow, and metabolic activity [7], then this helps explain why phenotypic presence of VAT is often considered the fat depot best correlated with adverse metabolic health consequences. The most common clinical measure of VAT is waist circumference. When waist circumference is increased beyond race-specific cutoff points, then this is often termed ‘central obesity’ and reflects the metric beyond which pathologic adverse metabolic consequences are more likely to ensue within a population [22▪]. However, although central obesity may be a phenotypic reflection of the adverse metabolic consequences of increased adiposity, this does not mean that an increase in central obesity is a reflection of adipose tissue pathologic processes exclusive to VAT. Waist circumference not only measures VAT, but also measures abdominal SAT. If only VAT was pathologic, and if all SAT were protective, then the adverse health consequences of waist circumference would require subtracting the contribution of the ‘protective’ abdominal SAT from total waist circumference. However, accumulation of abdominal SAT (especially, deep-layer SAT) is a strong predictor of global insulin resistance, liver-specific insulin resistance, Framingham Risk Score, and has higher expression of proinflammatory, lipogenic, and lipolytic genes, and contains higher proportions of saturated fatty acids [23]. These are not unlike the pathologic findings often described with VAT.

Also, amongst patients with the adiposopathic clustering of CVD risk factors, SAT often exhibits a pathogenic endocrine and immune profile (not a ‘protective’ profile). Specifically, in patients with metabolic syndrome, SAT may have increased macrophage recruitment, increased SAT-secreted adipokines, and decreased SAT adiponectin secretion, all of which contribute to a proinflammatory and insulin-resistant state [24▪▪]. Moreover, when SAT is unable to adequately store excessive energy because of impaired or limited adipocyte proliferation and differentiation [25], then this suggests an underlying type of ‘acquired lipodystrophy’ [26]. Limited SAT adipogenesis during positive caloric balance may lead to pathologic hypertrophy of existing fat cells [25], and energy overflow (e.g. increased circulating free fatty acid delivery) [27] to other body organs and other fat depots. Adiposopathic SAT endocrinopathies, inflammation, and energy overflow to pericardial fat, perivascular fat, and myocardial fat may directly contribute to atherosclerotic CVD [1,28,29]. Increased circulating free fatty acids to other body organs such as the liver, muscle, and pancreas may also result in lipotoxicity [30,31]. Lipotoxicity promotes the most common metabolic diseases encountered in clinical practice (e.g. high blood sugars, high blood pressure, and dyslipidaemia), which are major CVD risk factors that may indirectly contribute to CVD [1,14]. Finally, SAT endocrinopathies, inflammation [32], and energy overflow may increase VAT itself, resulting in central obesity, which may contribute to metabolic diseases and increased CVD risk [1,2,14,16]. This helps explain why waist circumference has scientific rationale as a clinically reliable, time-tested clinical measure of the pathogenic potential of adipose tissue amongst populations.

With further regard to lipotoxicity, intra-adipocyte lipolysis occurs when adipose triglyceride lipase hydrolyses triglycerides into diacylglyceride, which undergoes further breakdown by hormone-sensitive lipase (stimulated by beta-adrenergic signalling and suppressed by insulin signalling) into free fatty acids, which are released in the circulation, bound to albumin, and then delivered to other body tissues such as muscle for oxidation or liver for oxidation and triglyceride synthesis. (Glycerol is delivered to the liver for glucose production [7].) VAT is often described as more pathogenic than SAT because VAT adipocytes are reported to have higher basal lipolysis, greater sensitivity to catecholamines, and less sensitivity to insulin [33], leading to increased release of lipotoxic free fatty acids. Furthermore, because of its unique blood drainage through the portal system, VAT is often described as uniquely flooding the liver with free fatty acids through the portal system, again, leading to lipotoxicity to the liver, which then leads to insulin resistance and dyslipidaemia [33]. However, although some studies suggest VAT is less sensitive to the antilipolytic effects of insulin [7], other studies (at least in nonobese individuals) suggest insulin signalling may be greater in VAT than SAT [34]. Also, whereas VAT has predominantly portal venous return, SAT has both systemic and portal venous return. Given that SAT is often about 80% of total fat mass compared to about 10–20% for VAT, the vast majority of systemic circulating free fatty acid delivery to extrahepatic organs (for example muscle) originates from SAT, not VAT [2,35]. Thus, to the extent that extrahepatic lipotoxicity contributes to total body insulin resistance, SAT is more ‘pathologic’ than VAT. Even within the portal system, the majority of free fatty acids delivered to the liver are from SAT, not VAT [36]. Thus, regarding lipotoxicity and adverse metabolic consequences [37▪], SAT has substantial pathogenic potential and is not always ‘protective’.

Finally, if SAT was ‘protective’ and VAT was ‘pathogenic’, then a straight-forward therapeutic intervention would be to simply remove VAT, which should logically ‘cure’ associated metabolic abnormalities. However, at least in humans, surgical removal of omental fat does not improve insulin sensitivity and cardiovascular risk factors in obese adults [38]. This supports VAT as being a surrogate for global fat dysfunction, rather than a uniquely pathogenic organ. It helps explain why the best surgical interventions to improve adiposopathic metabolic abnormalities are those that reduce total body fat, as often achieved with bariatric surgery, which represents among the most effective treatment for metabolic disease, and CVD risk reduction in individuals who are overweight or obese [39].

In summary, a lack of SAT expandability and its associated endocrinopathies and immunopathies are pathologic in promoting metabolic disease [18]. It is the lack of adequate fat storage in SAT which results in increases in fatty infiltration of nonadipose tissue organ (e.g. liver, muscle, pancreas, heart, and kidney), as well as increased accumulation of other fat depots (e.g. pericardiac, perivascular fat), including increased VAT accumulation. At minimum, both SAT and VAT have potential protective and pathologic properties, with their potential for contributions to health and ill-health being interdependent. So, rather than binary labelling of any fat depot as being ‘protective’ or ‘pathologic’, different adipose tissue compartments might best be considered heterogeneous in their potential to contribute to metabolic disease [18]. As such, an increase in VAT accumulation is a surrogate measure of global fat dysfunction, and central obesity is a clinical marker for adiposopathy.

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If multiple fat depots are potentially pathogenic, then what diagnostic measures are most clinically useful to assess adipose tissue's global pathogenic potential?

Visceral adiposity is one of two of the sentinel anatomic findings of adiposopathy. Fat cell hypertrophy is another [2] (see Fig. 1). This suggests adipocyte size, based upon adipose tissue biopsy, may be useful in diagnosing adiposopathy. Increased fat cell size often accompanies increased circulating free fatty acids and ‘ectopic’ fat accumulation (i.e. visceral, pericardiac, perivascular, as well as intraorgan fat accumulation in liver, muscle, pancreas, heart, and kidney). Excessive fat cell enlargement may lead to adipocyte hypoxia and ‘stress’ to intra-adipocyte organelles, such as endoplasmic reticulum and mitochondria. These adiposopathic derangements contribute to endocrine and immune responses, metabolic disease, and increased CVD risk [1,40–42]. Consistent with the theme that the pathogenic potential of adipose tissue is best viewed collectively, rather than depot by depot, adipocyte mitochondrial oxidative capacity is reduced in both SAT and VAT amongst those with obesity. This impairment of adipocyte intraorganelle function does not appear to be because of differences in fat cell size, but rather because of increased global adiposity [43].

However, adipogenesis is a process that includes both proliferation and differentiation, both influenced by genetic and environmental factors [1,2]. Impairment of either of these processes may contribute to adiposopathic and lipodystrophic effects. So, although impaired adipogenesis and proliferation may lead to adipocyte hypertrophy (a classic anatomic finding for adiposopathy), impaired adipocyte differentiation may also result in adipocyte dysfunction, albeit not necessarily manifest by an increase in adipocyte size. Thus, although the finding of smaller fat cells is generally regarded as more functional, this may not always be the case. HIV lipodystrophy treated with certain antiretroviral therapies is illustrative of a disease process and intervention manifest by impairment of adipocyte differentiation (with a reduction in mean fat cell size), possible decrease in adipocyte proliferation, decrease in SAT accumulation, and an increase in VAT accumulation, all resulting in adiposopathic onset of hyperglycaemia and dyslipidaemia [44]. Measures of adipocyte functionality via gene expression of various markers assessed from adipose tissue biopsy may conceivably prove to be clinically useful; however, adipocyte biopsy histologic assessment of adipocyte size alone may not always be sufficiently diagnostic for fat cell function and dysfunction.

Other potential measures of adiposopathy might include the assessment of nonadipose, intraorgan fat. In addition to the SAT-mediated accumulation of non-SAT fat depots (e.g. perivascular, pericardial, and visceral depots), increased circulating free acids may contribute to pathogenic intraorgan fat to the liver, muscle, pancreas, heart, and kidney [1–4]. As noted previously, an increase in visceral fat may reflect SAT adiposopathic endocrine, immune, and adipogenic dysfunctions. Similarly, an increase in hepatic or muscle fat may likewise reflect SAT adiposopathic dysfunction. Increased body fat associated with an increase in liver fat increases metabolic diseases risk [45] and an increase in liver fat may be more linked with metabolic complications than visceral fat [46]. Conversely, if an increase in body fat is not associated with an increase in liver fat, then this may reflect sufficient functionality of SAT and/or ‘flexibility’ of the liver to manage any increased fatty acid delivery, both which would be expected to mitigate metabolic disease [47]. The same principle may apply to the degree by which muscle is ‘flexible’ in metabolizing triglycerides, which may help distinguish between patients with increased body fat and metabolic disease (e.g. prediabetes), versus those with normal glucose tolerance [48]. Thus, a potential alternative to waist circumference to measure adiposopathy and global fat dysfunction may be hepatic imaging studies and or liver and muscle biopsies to assess intraorgan fat. Amongst these choices, hepatic imaging (e.g. ultrasound or magnetic resonance spectroscopy) is the least invasive.

In summary, although body fat can be assessed by imaging studies [e.g. computerized tomography, MRI, magnetic resonance spectroscopy, and dual-energy X-ray absorptiometry (DEXA)], waist circumference has proven to be a validated clinical measure of the pathogenic potential of adipose tissue amongst populations, especially as it relates to metabolic disease and CVD risk. Also, waist circumference has the practical advantage as being reasonably applicable to the clinical setting. For the reasons previously discussed, hepatic imaging for hepatic fat may also play a role. Although increased adipocyte size highly correlates with intraorgan fat accumulation (both being potentially pathogenic) [49], biopsies of adipose tissue is mainly limited for research purposes, and not currently accepted as routine clinical measures of adiposopathy and global fat dysfunction. The same applies to muscle and liver biopsy.

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VAT accumulation may share similar adipose tissue pathologic processes leading to pericardiac and perivascular fat accumulation, as well as fatty infiltration of the liver, muscle, pancreas, heart, and kidney. Both SAT and VAT have potential protective and pathogenic effects [5,6]. Whereas hepatic imaging for liver fat and DEXA studies may assist in the diagnosis of adiposopathy, and although biopsy of fat, muscle, and liver may have relevance from a research perspective, the most clinically practical measure of adiposopathy is waist circumference (at least for overweight patients with BMI ≤35 kg/m2) [50]. That is because increased VAT is a surrogate marker for global fat dysfunction, and central obesity is a validated and time-tested clinical marker of adiposopathy and its adverse metabolic and CVD health consequences.

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Conflicts of interest

There are no conflicts of interest.

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Papers of particular interest, published within the annual period of review, have been highlighted as:

  • ▪ of special interest
  • ▪▪ of outstanding interest
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1. Bays HE. Adiposopathy is ‘sick fat’ a cardiovascular disease? J Am Coll Cardiol 2011; 57:2461–2473.
2. Bays HE, Gonzalez-Campoy JM, Bray GA, 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.
3. Wickman C, Kramer H. Obesity and kidney disease: potential mechanisms. Semin Nephrol 2013; 33:14–22.
4. Gastaldelli A, Morales MA, Marraccini P, Sicari R. The role of cardiac fat in insulin resistance. Curr Opin Clin Nutr Metab Care 2012; 15:523–528.
5. Coppack SW. Adipose tissue changes in obesity. Biochem Soc Trans 2005; 33:1049–1052.
6. Guri AJ, Bassaganya-Riera J. Systemic effects of white adipose tissue dysregulation and obesity-related inflammation. Obesity (Silver Spring) 2011; 19:689–700.
7. Lee MJ, Wu Y, Fried SK. Adipose tissue heterogeneity: implication of depot differences in adipose tissue for obesity complications. Mol Asp Med 2013; 34:1–11.
8. Bays HE, Fox KM, Grandy S. Anthropometric measurements and diabetes mellitus: clues to the ‘pathogenic’ and ‘protective’ potential of adipose tissue. Metab Syndr Relat Disord 2010; 8:307–315.
9. Fox CS, Massaro JM, Hoffmann U, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 2007; 116:39–48.
10. Jensen MD. Normal weight obesity. Cardiometab Risk 2009; 2:23–30. Available at: [Accessed 26 January 2014].
11▪. Seger JC, Horn DB, Westman EC, et al. Obesity algorithm, presented by the American Society of Bariatric Physicians. Version 2013–2014. [Accessed 31 January 2014].

The free online ASBP ‘Obesity Algorithm’ provides clinicians a practical clinical tool toward the assessment and management of patients with overweight or obesity.

12. Lu Q, Li M, Zou Y, Cao T. Induction of adipocyte hyperplasia in subcutaneous fat depot alleviated type 2 diabetes symptoms in obese mice. Obesity (Silver Spring) 2014; 22:1623–1631.
13. Bays H, Ballantyne C. Adiposopathy: why do adiposity and obesity cause metabolic disease? Future Lipidol 2006; 1:389–420.
14. Bays HE. ‘Sick fat’, metabolic disease, and atherosclerosis. Am J Med 2009; 122:S26–S37.
15. Bays HE, Toth PP, Kris-Etherton PM, et al. Obesity, adiposity, and dyslipidemia: a consensus statement from the National Lipid Association. J Clin Lipidol 2013; 7:304–383.
16. Bays HE. Adiposopathy, diabetes mellitus, and primary prevention of atherosclerotic coronary artery disease: treating ‘sick fat’ through improving fat function with antidiabetes therapies. Am J Cardiol 2012; 110:4B–12B.
17. Denis GV, Obin MS. ‘Metabolically healthy obesity’: origins and implications. Mol Asp Med 2013; 34:59–70.
18. Patel P, Abate N. Role of subcutaneous adipose tissue in the pathogenesis of insulin resistance. J Obes 2013; 2013:489187.
19▪. Roberson LL, Aneni EC, Maziak W, et al. Beyond BMI: The ‘Metabolically healthy obese’ phenotype & its association with clinical/subclinical cardiovascular disease and all-cause mortality – a systematic review. BMC Public Health 2014; 14:14.

This analysis suggests patients who are ‘metabolically healthy and overweight’ may not be so healthy.

20▪. Kramer CK, Zinman B, Retnakaran R. Are metabolically healthy overweight and obesity benign conditions?: a systematic review and meta-analysis. Ann Int Med 2013; 159:758–769.

This analysis suggests patients who are ‘metabolically healthy and overweight’ may not be so healthy.

21. Tchoukalova YD, Koutsari C, Karpyak MV, et al. Subcutaneous adipocyte size and body fat distribution. Am J Clin Nutr 2008; 87:56–63.
22▪. Bays H. Adiposopathy, ‘Sick Fat’, Ockham's Razor, and resolution of the Obesity Paradox. Curr Atheroscler Rep 2014; 16:409.

Adiposopathy is the most common cause of high glucose, high blood pressure, and dyslipidaemia.

23. Marinou K, Hodson L, Vasan SK, et al. Structural and functional properties of deep abdominal subcutaneous adipose tissue explain its association with insulin resistance and cardiovascular risk in men. Diabetes Care 2013.
24▪▪. Bremer AA, Jialal I. Adipose tissue dysfunction in nascent metabolic syndrome. J Obes 2014; [Epub ahead of print].

Amongst patients with metabolic syndrome, subcutaneous adipose tissue expresses an adipokine profile that may contribute to increased insulin resistance and low-grade inflammation, which in turn promotes an increased risk of type 2 diabetes mellitus and cardiovascular disease.

25. Gustafson B, Gogg S, Hedjazifar S, et al. Inflammation and impaired adipogenesis in hypertrophic obesity in man. Am J Physiol Endocrinol Metab 2009; 297:E999–E1003.
26. 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–S21.
27. Kazantzis M, Stahl A. Fatty acid transport proteins, implications in physiology and disease. Biochim Biophys Acta 2012; 1821:852–857.
28. Szasz T, Webb RC. Perivascular adipose tissue: more than just structural support. Clin Sci (Lond) 2012; 122:1–12.
29. Cherian S, Lopaschuk GD, Carvalho E. Cellular cross-talk between epicardial adipose tissue and myocardium in relation to the pathogenesis of cardiovascular disease. Am J Physiol Endocrinol Metab 2012; 303:E937–E949.
30. Bays H, Mandarino L, DeFronzo RA. Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. J Clin Endocrinol Metab 2004; 89:463–478.
31. Yang J, Kang J, Guan Y. The mechanisms linking adiposopathy to type 2 diabetes. Front Med 2013; 7:433–444.
32. Le KA, Mahurkar S, Alderete TL, et al. Subcutaneous adipose tissue macrophage infiltration is associated with hepatic and visceral fat deposition, hyperinsulinemia, and stimulation of NF-kappaB stress pathway. Diabetes 2011; 60:2802–2809.
33. McCarty MF. Modulation of adipocyte lipoprotein lipase expression as a strategy for preventing or treating visceral obesity. Med Hypotheses 2001; 57:192–200.
34. Laviola L, Perrini S, Cignarelli A, et al. Insulin signaling in human visceral and subcutaneous adipose tissue in vivo. Diabetes 2006; 55:952–961.
35. Klein S. The case of visceral fat: argument for the defense. J Clin Invest 2004; 113:1530–1532.
36. Ebbert JO, Jensen MD. Fat depots, free fatty acids, and dyslipidemia. Nutrients 2013; 5:498–508.
37▪. Gaggini M, Morelli M, Buzzigoli E, et al. Nonalcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients 2013; 5:1544–1560.

The lipotoxic effects of increased circulating free fatty acids induces adiposopathy intraorganelle dysfunction (e.g. mitochondrial dysfunction) and increases fatty acid accumulation in nonadipose organs; patients with nonalcoholic fatty liver disease is often accompanied by fat accumulation in the heart and pancreas.

38. Fabbrini E, Tamboli RA, Magkos F, et al. Surgical removal of omental fat does not improve insulin sensitivity and cardiovascular risk factors in obese adults. Gastroenterology 2010; 139:448–455.
39. Bays HE, Laferrere B, Dixon J, et al. Adiposopathy and bariatric surgery: is ‘sick fat’ a surgical disease? Int J Clin Pract 2009; 63:1285–1300.
40. Bluher M. Adipose tissue dysfunction contributes to obesity related metabolic diseases. Best Pract Res Clin Endocrinol Metab 2013; 27:163–177.
41. O’Connell J, Lynch L, Cawood TJ, et al. The relationship of omental and subcutaneous adipocyte size to metabolic disease in severe obesity. PLoS One 2010; 5:e9997.
42. De Ferranti S, Mozaffarian D. The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences. Clin Chem 2008; 54:945–955.
43. Yin X, Lanza IR, Swain JM, et al. Adipocyte mitochondrial function is reduced in human obesity independent of fat cell size. J Clin Endocrinol Metab 2014; [Epub ahead of print].
44. Caso G, Mileva I, McNurlan MA, et al. Effect of ritonavir and atazanavir on human subcutaneous preadipocyte proliferation and differentiation. Antivir Res 2010; 86:137–143.
45. Schattenberg JM, Schuppan D. Nonalcoholic steatohepatitis: the therapeutic challenge of a global epidemic. Curr Opin Lipidol 2011; 22:479–488.
46. Fabbrini E, Magkos F, Mohammed BS, et al. Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. Proc Natl Acad Sci USA 2009; 106:15430–15435.
47. Magkos F, Fabbrini E, Mohammed BS, et al. Increased whole-body adiposity without a concomitant increase in liver fat is not associated with augmented metabolic dysfunction. Obesity (Silver Spring) 2010; 18:1510–1515.
48. Perreault L, Bergman BC, Hunerdosse DM, et al. Inflexibility in intramuscular triglyceride fractional synthesis distinguishes prediabetes from obesity in humans. Obesity (Silver Spring) 2010; 18:1524–1531.
49. Petaja EM, Sevastianova K, Hakkarainen A, et al. Adipocyte size is associated with NAFLD independent of obesity, fat distribution, and PNPLA3 genotype. Obesity (Silver Spring) 2013; 21:1174–1179.
50. Jensen MD, Ryan DH, Apovian CM, et al. 2013AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol 2014; [Epub ahead of print].

adiposopathy; central obesity; obesity; visceral adipose tissue

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