Leptin-melanocortin pathway plays an essential role in the body weight regulation. Enhanced melanocortin signaling in the hypothalamus results in both decreased food intake and increased energy expenditure. The discovery of monogenic obesities with dysfunction of melanocortin-4 receptor (MC4R) greatly contributed to understanding of energy balance regulation. This review presents phenotypical characterization and prevalence of the MC4R gene mutations. Genome-wide association studies revealed that MC4R gene is significantly related not only to monogenic obesities but also to common obesity. An interaction of variants in the MC4R gene with fat mass and obesity associated (FTO) gene significantly increases the risk for obesity, particularly in adolescence. On the other hand, about 15 % of the MC4R gene variants result in a gain of function that protects against obesity and is associated with favorable metabolic profile. Long-term attempts to activate the MC4R have recently been finalized by a discovery of setmelanotide, a novel specific MC4R agonist that is devoid of untoward cardiovascular side-effects. The employment of specific MC4R agonists may open new horizons not only in the treatment of rare monogenic obesities but also in some common obesities where stimulation of MC4R could be achieved., Vojtěch Hainer, Irena Aldhoon Hainerová, Marie Kunešová, Radka Taxová Braunerová, Hana Zamrazilová, Běla Bendlová., and Obsahuje bibliografii
The fatty acid composition is associated with obesity. Omega 3 polyunsaturated fatty acid (PUFA) could have a beneficial role in the prevention and treatment of many disorders, including cardiometabolic diseases. A cohort of 84 men and 131 women were examined in adolescence and after 8 years. Body weight (BW) and fat mass (FM) were measured. The composition of fatty acids (FAs) of serum phospholipids was assessed using gas chromatography. Statistics: PLS method. Aim: to determine the relationships between FAs in adolescence and FM (explanatory variable 1, EV1) and BW (explanatory variable 2, EV2) in adulthood. In the predictive models, a cluster of FAs in boys explained 47.2 % of EV1 and a cluster of 6 FAs in girls explained 32.3 % of EV1 measured in adulthood. FAs measured in adolescents explained 23.7 % of EV2 in early adults regardless of gender. A significant negative association was found between 18:1n-9c and EV1 in males and EV2 in both genders. We found a significant negative association between 18:2n-6 and 20:0 and both EV1 and EV2. In all analyses, we found a significant negative association of 20:1n-9 and 18:3n-3 with EV1-2 in both genders. A significant positive association was found in 20:3n-6 with EV1 and EV2 in males. 20:4n-6 was positively associated with EV1 in females and EV2 in both genders. A positive association between FM and very long chain n- 6 PUFAs was also observed. It is concluded that serum MUFAs and essential PUFAs in adolescence are associated with lower BW and FM in adulthood.