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A subgroup of obese subjects which could be protected from the cardiometabolic complications of obesity is described in the literature as "metabolically normal obese subjects". However, the lack of a joint definition of metabolic normality makes the available data difficult to interpret and to compare. A recent analysis of more than 1200 subjects in a prospective study showed that 21% of obese metabolically normal subjects at baseline developed the metabolic syndrome after three years. The obese subjects who remained metabolically normal showed, at three years, significantly higher values of cardiometabolic parameters as compared to subjects with normal body weight. In conclusion, the obese subjects even without any metabolic abnormality should benefit of a closer medical monitoring as well as a regular follow-up to avoid further weight gain.

The control of the appetite by drugs (sensation of hunger, satiation and satiety) is crucial in the management of obesity. Numerous drugs in this domain were forbidden these last years because of serious side effects. New researches allow the development of new substances presenting fewer side effects either by better specificity on receptors (locarserin), or by new mechanism of action (GLP-1, leptin, anti Ghrelin). The appetite is settled by a complex neurohormonal mechanism. To act on some systems at the same time, the development of products "polypill" combining naltroxone-bupropion, phentermine-topiramate or amylin-leptine give encouraging results. However the dominant mechanism of the appetite dysregulation needs to be better understood.

A successful weight loss program leads to a new metabolic and endocrine balance that needs new long term management. Recent researches have shown some predictors as well as some barriers of the long term weight management. Predictors and barriers are linked to the lost weight, to the subject's habits and to the patient's psychosocial sphere. During the four-year follow-up, 78% of patients maintained 10% or more of their initial weight loss. The patients who maintained their weight presented less binge eating disorder, good motivation in diet and physical activity.

Obesity is well recognized as a cardiovascular risk factor and being associated with cardio-metabolic diseases. However, certain authors describe the existence of metabolically benign obesity or not-complicated obesity. By examining various studies, one of the encountered difficulties is the criteria of normality among obese patients and the evaluated metabolic parameters. Even if traditional cardio-metabolic parameters such as the lipid profile, glycemia or blood pressure can be in normal ranges, the subjects in overweight or obesity are different from the subjects of normal body weight in terms of these parameters which are at the limit of normality. The purpose of this article is to summarize the current concepts of metabolic normality in obese subjects. We conclude that the body weight is the most important factor in the development of the cardio-metabolic consequences of obesity.

Obesity is a recognized risk factor for cardiovascular diseases. As evaluated by body mass index (BMI), obesity is associated with increased morbidity and mortality due to chronic diseases, like type 2 diabetes, coronary artery disease and stroke. It has been shown that not only the quantity of the fat mass but also the fat mass distribution is important. Furthermore, the fat tissue deposition at visceral level, as measured by waist circumference, is a risk factor for cardio-metabolic diseases. The waist circumference is easy to measure and reflect the visceral adipose tissue which is a cardio-metabolic risk factor Abdominal fat accumulation induces a less favorable cardio-metabolic profile, even in normal body weight subjects with waist circumference within the normal range.

CBI endocannabinoid system receptors localized in the hypothalamus and the nucleus accumbens are known to regulate hunger. Hyperstimulation of the CBI receptors lead to an increase of food intake, but also to an increase of lipogenesis, decrease of adiponectin and increase of insulin resistance. Rimonabant is the first CBI central and peripheral blocker, tested in international trials (RIO-lipids, RIO-Europe and RIO-North America). Significant results on weight reduction, increased adiponectin and improved metabolic syndrome have been demonstrated. Rimonabant is a new pharmacological therapy and very interesting for tackling obesity and metabolic syndrome.