Metabolically Healthy Obesity—Does it Exist?
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The prevalence of obesity has been increasing worldwide over the past 30 years and is a major public health concern. Obesity is known to be associated with metabolic disturbances including insulin resistance and inflammation; however, there is a subset of obese subjects who have normal metabolic profiles, and they have been identified as the metabolically healthy obese (MHO). Several studies have described MHO as obese individuals who have high levels of insulin sensitivity and the absence of diabetes, dyslipidemia, or hypertension. The prevalence of MHO varies from 20 to 30 % among obese individuals. This review will discuss the MHO phenotype; the differences between MHO and metabolically unhealthy obese (MUO) individuals; and the possible underlying mechanisms including adipocyte differentiation, immune regulation, and cellular energy metabolism.
KeywordsMetabolically healthy obese Insulin resistance Adipose tissue inflammation
The authors would like to thank Barbara S. Nikolajczyk Ph.D. for the editorial assistance.
Compliance with Ethics Guidelines
Conflict of Interest
Patchaya Boonchaya-anant declares no conflict of interest. Caroline M. Apovian received grants from Orexigen Therapeutics, GI Dynamics, MetaProteomics, Eli Lilly, Sanofi Aventis, Amylin, and Aspire Bariatrics and received personal fees from Orexigen Therapeutics, Johnson and Johnson, Nutrisystem, GI Dynamics, EnteroMedics, Zafgen, Arena, Merck, Sanofi Aventis, Amylin, and Atkins Foundation.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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- 1.•Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014.Google Scholar
- 22.Le KA, Mahurkar S, Alderete TL, Hasson RE, Adam TC, Kim JS, 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(11):2802–9.PubMedCentralPubMedCrossRefGoogle Scholar
- 23.Wildman RP, Muntner P, Reynolds K, McGinn AP, Rajpathak S, Wylie-Rosett J, et al. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999–2004). Arch Intern Med. 2008;168(15):1617–24.PubMedCrossRefGoogle Scholar
- 36.Aung K, Lorenzo C, Hinojosa MA, Haffner SM. Risk of developing diabetes and cardiovascular disease in metabolically unhealthy normal-weight and metabolically healthy obese individuals. J Clin Endocrinol Metab. 2013;jc20132832.Google Scholar
- 38.Roberson LL, Aneni EC, Maziak W, Agatston A, Feldman T, Rouseff M, 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(1):14.PubMedCentralPubMedCrossRefGoogle Scholar
- 40.Bell JA, Kivimaki M, Hamer M. Metabolically healthy obesity and risk of incident type 2 diabetes: a meta-analysis of prospective cohort studies. Obes Rev: Off J In Assoc Study Obes. 2014.Google Scholar
- 41.••Hinnouho GM, Czernichow S, Dugravot A, Batty GD, Kivimaki M, Singh-Manoux A. Metabolically healthy obesity and risk of mortality: does the definition of metabolic health matter? Diabetes Care. 2013;36(8):2294–300. This study compared five definitions of MHO and examined the differences in outcome of all-cause and cardiovascular mortality.Google Scholar
- 45.Phillips CM, Perry IJ. Does inflammation determine metabolic health status in obese and nonobese adults? J Clin Endocrinol Metab. 2013.Google Scholar
- 58.Kintscher U, Hartge M, Hess K, Foryst-Ludwig A, Clemenz M, Wabitsch M, et al. T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol. 2008;28(7):1304–10.PubMedCrossRefGoogle Scholar
- 67.Gauthier MS, O’Brien EL, Bigornia S, Mott M, Cacicedo JM, Xu XJ, et al. Decreased AMP-activated protein kinase activity is associated with increased inflammation in visceral adipose tissue and with whole-body insulin resistance in morbidly obese humans. Biochem Biophys Res Commun. 2011;404(1):382–7.PubMedCentralPubMedCrossRefGoogle Scholar
- 72.Maassen JA, Romijn JA, Heine RJ. Fatty acid-induced mitochondrial uncoupling in adipocytes as a key protective factor against insulin resistance and beta cell dysfunction: a new concept in the pathogenesis of obesity-associated type 2 diabetes mellitus. Diabetologia. 2007;50(10):2036–41.PubMedCentralPubMedCrossRefGoogle Scholar
- 73.Soronen J, Laurila PP, Naukkarinen J, Surakka I, Ripatti S, Jauhiainen M, et al. Adipose tissue gene expression analysis reveals changes in inflammatory, mitochondrial respiratory and lipid metabolic pathways in obese insulin-resistant subjects. BMC Med Genet. 2012;5:9.Google Scholar
- 75.Schroder H, Ramos R, Baena-Diez JM, Mendez MA, Canal DJ, Fito M, et al. Determinants of the transition from a cardiometabolic normal to abnormal overweight/obese phenotype in a Spanish population. Eur J Nutr. 2013.Google Scholar
- 79.••Brethauer SA, Aminian A, Romero-Talamas H, Batayyah E, Mackey J, Kennedy L, et al. Can diabetes be surgically cured? Long-term metabolic effects of bariatric surgery in obese patients with type 2 diabetes mellitus. Ann Surg. 2013;258(4):628–36; discussion 36–7. This study reports that bariatric surgery can induce a remission and improvement of type 2 diabetes and metabolic parameters in obese patients.Google Scholar