• Cardiometabolic Disorder

• Cardiometabolic Disorder
• Endocrinology
• Diabetes & Metabolic Syndrome

André Tchernof, PhD, Université Laval, Laval, Québec, Canada, discussed visceral adipose tissue metabolism and its association with cardiometabolic risk.

Visceral obesity is associated with a variety of conditions that increases the risk developing type 2 diabetes and cardiovascular disease [Kissebah AH, Krakower GR. Physiol Rev 1994; Després JP, Lemieux I. Nature 2006; Tchernof A, Després JP. Physiol Rev 2013]. These features include:

• ▪ Glucose intolerance

• ▪ Insulin resistance

• ▪ Hyperinsulinemia

• ▪ Dyslipidemia

• ▪ Hypertension

• ▪ Proinflammatory and prothrombotic state

• ▪ Hepatic stenosis

Regional differences in the average size and number of adipocytes found in subcutaneous and visceral adipose tissue have been described [Tchernof A. Sex differences in energy balance, body composition, and body fat distribution. In: Tsatsoulis A, Wyckoff J, Brown FM, eds. Diabetes in Women. USA: Springer; 2010: 1–24.]. Other mechanisms by which obesity may increase cardiometablic risk include changes in lipoprotein lipase activity and in the release of free fatty acids, adiponectin, and interleukin-6 that occur in obese patients.

Increasing body fat mass is associated with increased adipocyte diameter. In addition, there is an increased number of larger diameter adipocytes in subcutaneous and visceral adipose tissue [Spalding KL et al. Nature 2008; Veilleux A et al. Diabetes 2011]. The enlargement of existing adipocytes—adipocyte hypertrophy—that occurs in visceral fat maybe associated with an altered lipid profile independent of body composition and fat distribution in women [Veilleux A et al. Diabetes 2011].

Visceral adipocyte hypertrophy is associated with a hyperlipolytic response to beta-adrenergic and post-receptor agents in adipose cells as well as elevated expression of CCAAT enhancer-binding protein beta (C/EBPB), and reduced expression of glucose transporter type 4 in subcutaneous adipose tissue. In addition, visceral adipocyte hypertrophy is associated with elevated expression of CD31 and von Willebrand factor in subcutaneous and omental adipose, and elevated expression of CD68 in omental adipose.

In the metabolic syndrome, adipocyte hypertrophy plays a role in lipid uptake and lipolytic rate of adipocytes [Varlamov O et al. Am J Physiol Endocrinol Metab 2010; Tchernof A et al. Diabetes 2006], release of adiponectin and leptin [Drolet R et al. Obesity 2009; Lee MJ, Fried SK. Am J Physiol Endocrinol Metab 2009], macrophage infiltration [Michaud A et al. Metabolism 2012], insulin resistance [McLaughlin T et al. Diabetologia 2007], and dyslipidemia [Veilleux A et al. Diabetes 2011].

Adipocyte hyperplasia is associated with subcutaneous fat in men and women. Prof. Tchernof noted that in many instances visceral adipocyte hypertrophy is a stronger predictor of metabolic alterations than subcutaneous adipocyte hypertrophy. Visceral fat quickly becomes inefficient for lipid storage as its mass and the size of its adipocytes increase, perhaps because expansion is mostly through lipogenesis.

It is important to note that the previously described results have been obtained in lean-to-moderately obese subjects, in whom fat cell size tends to increase linearly with adiposity. The same relationship has not been described in more obese individuals where the predictive ability and pathophysiological importance of fat cell size may differ.

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