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Metabolically healthy obesity refers to an obesity phenotype with no or little evidence of metabolic dysfunction. Lower liver fat content and visceral adipose tissue, greater insulin sensitivity and secretion, greater cardiorespiratory fitness, and a predominantly lower body (i.e. leg) fat deposition are key physiological traits of a metabolically healthy phenotype. About 35% of all subjects with obesity are metabolically healthy. These individuals have approximately half the risk of developing type 2 diabetes and cardiovascular disease compared with metabolically unhealthy subjects with obesity, but they still have a significantly greater risk (by 50–300%) compared with metabolically healthy lean subjects. Therefore, absence of metabolic risk factors in people with obesity should not be a contraindication for weight-loss treatment. Metabolically healthy obesity needs to be treated, and this need is reinforced by the fact that this phenotype is not stable over time, as ∼50% of these subjects will cease being metabolically healthy within ∼10 y. Intervening early is therefore important. Weight loss dose-dependently decreases visceral adipose tissue and liver fat content, and it improves multiorgan insulin sensitivity and β-cell function (i.e. it beneficially affects many of the physiological traits of a metabolically healthy phenotype); however, weight loss is very difficult to maintain. This typically results in disappointment among patients and hinders adherence, which is likely critical for the limited success of most weight-loss treatments in the long term. On the other hand, using ≥1 metabolic health targets in a non-weight-loss-centered treatment paradigm that includes prudent dietary changes and increased physical activity can serve as an appropriate first goal that can help motivate patients toward the long-term goals of obesity treatment. [ABSTRACT FROM AUTHOR]

Background & Aims: An increased number of macrophages in adipose tissue is associated with insulin resistance and metabolic dysfunction in obese people. However, little is known about other immune cells in adipose tissue from obese people, and whether they contribute to insulin resistance. We investigated the characteristics of T cells in adipose tissue from metabolically abnormal insulin-resistant obese (MAO) subjects, metabolically normal insulin-sensitive obese (MNO) subjects, and lean subjects. Insulin sensitivity was determined by using the hyperinsulinemic euglycemic clamp procedure. Methods: We assessed plasma cytokine concentrations and subcutaneous adipose tissue CD4+ T-cell populations in 9 lean, 12 MNO, and 13 MAO subjects. Skeletal muscle and liver samples were collected from 19 additional obese patients undergoing bariatric surgery to determine the presence of selected cytokine receptors. Results: Adipose tissue from MAO subjects had 3- to 10-fold increases in numbers of CD4+ T cells that produce interleukin (IL)-22 and IL-17 (a T-helper [Th] 17 and Th22 phenotype) compared with MNO and lean subjects. MAO subjects also had increased plasma concentrations of IL-22 and IL-6. Receptors for IL-17 and IL-22 were expressed in human liver and skeletal muscle samples. IL-17 and IL-22 inhibited uptake of glucose in skeletal muscle isolated from rats and reduced insulin sensitivity in cultured human hepatocytes. Conclusions: Adipose tissue from MAO individuals contains increased numbers of Th17 and Th22 cells, which produce cytokines that cause metabolic dysfunction in liver and muscle in vitro. Additional studies are needed to determine whether these alterations in adipose tissue T cells contribute to the pathogenesis of insulin resistance in obese people. [Copyright &y& Elsevier]