Is adiposopathy (sick fat) an endocrine disease?

Abstract

Objective: To review current consensus and controversy regarding whether obesity is a 'disease', examine the pathogenic potential of adipose tissue to promote metabolic disease and explore the merits of 'adiposopathy' and 'sick fat' as scientifically and clinically useful terms in defining when excessive body fat may represent a 'disease'.

Methods: A group of clinicians and researchers, all with a background in endocrinology, assembled to evaluate the medical literature, as it pertains to the pathologic and pathogenic potential of adipose tissue, with an emphasis on metabolic diseases that are often promoted by excessive body weight.

Results: The data support pathogenic adipose tissue as a disease. Challenges exist to convince many clinicians, patients, healthcare entities and the public that excessive body fat is often no less a 'disease' than the pathophysiological consequences related to anatomical abnormalities of other body tissues. 'Adiposopathy' has the potential to scientifically define adipose tissue anatomic and physiologic abnormalities, and their adverse consequences to patient health. Adiposopathy acknowledges that when positive caloric balance leads to adipocyte hypertrophy and visceral adiposity, then this may lead to pathogenic adipose tissue metabolic and immune responses that promote metabolic disease. From a patient perspective, explaining how excessive caloric intake might cause fat to become 'sick' also helps provide a rationale for patients to avoid weight gain. Adiposopathy also better justifies recommendations of weight loss as an effective therapeutic modality to improve metabolic disease in overweight and obese patients.

Conclusion: Adiposopathy (sick fat) is an endocrine disease.

Figure 1

Anatomic manifestations of adiposopathy include adipocyte hypertrophy and visceral adiposity, which may lead to pathogenic metabolic and immune responses that promote metabolic disease (8). Positive caloric balance results in increased energy storage, which is initially manifested by mild adipocyte hypertrophy. This normally promotes paracrine signalling for adipogenesis (recruitment of new fat cells). Particularly when adipogenesis is impaired (3), continued positive caloric balance may worsen adipocyte hypertrophy, causing adipocytes to become dysfunctional and potentially pathogenic. Similarly, if excessive calories are stored in the visceral region, then this also is potentially pathogenic, and promotes metabolic disease. Excessive body fat may not be ‘healthy’ because of pathologic mass effects. However, accumulation of adipose tissue through adipocyte proliferation in the subcutaneous peripheral region may have less potential for promotion of metabolic disease, and may therefore be metabolically ‘healthier’. If during weight loss, subcutaneous peripheral adipose tissue is diminished and the proportion of visceral adipose tissue is increased, then this can also result in adiposopathy and promote metabolic disease, as is found with some cases of hypercortisolaemia and human immunodeficiency virus-associated lipodystrophy. Reproduced from Expert Rev. Cardiovasc. Ther. 4(6), 871–895 (2006) with permission of Expert Reviews Ltd

Figure 2

Adiposopathy is a disease that results in pathogenic metabolic and immune adipose tissue responses that promote metabolic disease (6). Age, gender, race, and genetic predisposition, and sedentary lifestyle are all examples of determinants as to how positive caloric balance may lead to adiposopathy. Pathogenic metabolic and immune responses associated with adiposopathy directly contribute to type 2 diabetes mellitus, hypertension, dyslipidaemia and potentially atherosclerosis. Reproduced from Future Lipidol. (2006) 1(4), 389–420 with permission of Future Medicine