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A Practical Guide to the Clinical Assessment and Investigation of Obesity 

A Practical Guide to the Clinical Assessment and Investigation of Obesity
A Practical Guide to the Clinical Assessment and Investigation of Obesity

I. Sadaf Farooqi

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date: 22 April 2021

As the prevalence of obesity is rising, we are seeing a greater proportion of patients with severe obesity. It is important to have a practical approach to the investigation and management of these vulnerable patients, who have considerably increased morbidity and mortality. There have been major advances in our understanding of the molecular basis for a number of complex obesity syndromes, such as Bardet-Beidl syndrome, which have provided novel insights into processes essential for human hypothalamic function and the regulation of body weight. We now realize that there is a whole group of monogenic obesity syndromes involving the leptin–melanocortin pathway where obesity itself is the presenting feature.

The practical implications of these findings for genetic counseling, prognostication, and even therapy have already emerged; and given the rapid pace of genetic and molecular technologies, it is very likely that new genes, proteins, and mechanisms will emerge to explain a variety of previously unrecognized obesity syndromes in the near future. As more is learned about these genes and more syndromes are described, it is likely that the need to evaluate severely obese patients in recognized centers will grow, and close collaboration with academic centers with experience in this field is needed to ensure that the benefits of laboratory research are made available to the patients who need them. The clinical evaluation of the severely obese patient will become increasingly sophisticated and require the development of expertise in the recognition of these emerging syndromes together with the incorporation of novel biochemical and molecular genetic diagnostics. These approaches will need to be combined with the more traditional nutritional and behavioral approaches to optimize treatment for individual patients.

Discovery or the causative genetic detect has led to dramatically successful mechanism-based therapy in a few individuals. Finally, mutations in one gene, the melanocortin 4 receptor, may be responsible for thousands of patients with obesity in the United Kingdom alone. Knowledge of the specific molecular mechanisms in this and other genetic disorders should lead to better mechanism-directed pharmacotherapy in the future.

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