The prevalence of obesity is increasing worldwide, affecting both children and adults. This obesity epidemic is mostly driven by an increase in energy intake (abundance of highly palatable energy-dens Show more
The prevalence of obesity is increasing worldwide, affecting both children and adults. This obesity epidemic is mostly driven by an increase in energy intake (abundance of highly palatable energy-dense food and drinks) and to a lesser degree a decrease in energy expenditure (sedentary lifestyle). A small proportion of individuals with obesity are affected by genetic forms of obesity, which often relate to mutations in the leptin-melanocortin pathway or are part of syndromes such as the Bardet-Biedl syndrome. These rare forms of obesity have provided valuable insights into the genetic architecture of obesity. Recent advances in understanding the molecular mechanisms that control appetite, hunger, and satiety have led to the development of drugs that can override genetic defects, enabling precision treatment. Leptin deficiency is uniquely treated with recombinant human metreleptin, while those with LEPR, PCSK1, or POMC deficiency can now be treated with the MC4R agonist setmelanotide. This review highlights the most frequent monogenic and syndromic forms of obesity, and the future outlook of precision treatment for these conditions. Show less
Obesity is a chronical disease, which leads to multiple short- and long-term complications. 4% of Swiss children and adolescents are obese. A prompt diagnosis and multicomponent lifestyle intervention Show more
Obesity is a chronical disease, which leads to multiple short- and long-term complications. 4% of Swiss children and adolescents are obese. A prompt diagnosis and multicomponent lifestyle intervention is mandatory to avoid persistence of the disease into adulthood. Growth and BMI charts are still the essential tools to diagnose and define the etiology of obesity. A precocious and severe obesity, accompanied by hyperphagia, will raise the suspicion of monogenic obesity. The precise molecular diagnosis enables in some patients the use of a specific treatment. Leptine in case of LEP gene defects, or setmelanotide when the affected gene is part of the MC4R signaling pathway (LEPR, POMC, PCSK1). Show less
The aim of this study was to perform familial co-segregation analysis and functional trial in vivo during mixed meal tolerance test (MMTT) of novel variants in diabetes candidate genes. It is a contin Show more
The aim of this study was to perform familial co-segregation analysis and functional trial in vivo during mixed meal tolerance test (MMTT) of novel variants in diabetes candidate genes. It is a continuation of the project "Genetic diabetes in Lithuania" with the cohort of 1209 patients with diabetes. Prior screening for autoimmune markers confirmed type 1 diabetes (T1D) diagnosis in 88.1% (n=1065) of patients, and targeted next-generation sequencing identified 3.5% (n=42) pathogenic variants in MODY genes. Subsequently, 102 patients were classified as having diabetes of unknown etiology. 12/102 were found to have novel variants in potential diabetes genes ( MMTT analysis showed that probands with variants in Functional beta-cell study in vivo allowed to select five most probable genes for monogenic diabetes. Familial co-segregation analysis showed that novel variant in Show less